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Infectious Disease and Microbiology – Acne Vulgaris
Acne vulgaris (common acne) is a chronic inflammatory disorder of the pilosebaceous unit, particularly the sebaceous follicles. It is characterized by comedones, papules, pustules, nodules, and in more severe cases, scarring. The condition primarily affects areas rich in sebaceous glands, including the face, neck, chest, upper back, and upper arms.
Acne is one of the most common skin diseases, affecting more than 85% of individuals at some point between adolescence and early adulthood, with a mean age of approximately 24 years. It accounts for up to 2 million office visits annually among adolescents aged 15–19 years. A major risk factor is increased responsiveness of sebaceous glands and keratinocytes to androgenic hormones, particularly during puberty. Elevated androgen levels such as testosterone, dehydroepiandrosterone sulfate (DHEAS), or androstenedione may worsen acne severity, especially in women.
The pathophysiology involves inflammatory changes within sebaceous follicles, leading to accumulation of lipid-rich sebum and proliferation of Cutibacterium acnes (formerly Propionibacterium acnes), a Gram-positive anaerobic bacterium that normally exists in low numbers on the skin. Overgrowth of this organism within the follicle triggers inflammation, follicular rupture, and extension of inflammation into the surrounding dermis. This process results in the formation of papules, pustules, and nodules.
Clinically, patients present with open comedones (blackheads) or closed comedones (whiteheads). As inflammation progresses, lesions may become painful and form pustules or nodules. Scarring suggests more aggressive disease. Acne is classified as mild when primarily noninflammatory comedones are present, moderate when inflammatory papules and pustules affect larger skin areas, and severe when large painful nodules with potential scarring are present.
Treatment depends on severity. Mild to moderate acne often responds to topical therapy, including retinoids, benzoyl peroxide, and topical antimicrobials. Retinoids reduce sebaceous gland activity and normalize follicular keratinization. Benzoyl peroxide acts as a bactericidal agent and is often combined with topical antibiotics to reduce resistance. More severe cases may require oral antibiotics such as doxycycline, minocycline, tetracycline, trimethoprim-sulfamethoxazole, erythromycin, or clindamycin, although resistance has become increasingly common.
For severe nodulocystic acne or cases associated with scarring, oral isotretinoin is indicated. It reduces sebaceous gland size and sebum production, inhibits bacterial growth, and has anti-inflammatory properties. However, isotretinoin is highly teratogenic and may cause hypertriglyceridemia. Women of childbearing age must use two forms of contraception during treatment. Reports have also suggested possible associations with mood changes.
Additional therapies may include spironolactone or oral contraceptives in patients with hyperandrogenism. Intralesional corticosteroids can be used for severe inflammatory nodules. With appropriate treatment and adherence, most patients experience significant improvement, and early management helps reduce the risk of permanent scarring.
Acne vulgaris (common acne) is a chronic inflammatory disorder of the pilosebaceous unit, particularly the sebaceous follicles. It is characterized by comedones, papules, pustules, nodules, and in more severe cases, scarring. The condition primarily affects areas rich in sebaceous glands, including the face, neck, chest, upper back, and upper arms.
Acne is one of the most common skin diseases, affecting more than 85% of individuals at some point between adolescence and early adulthood, with a mean age of approximately 24 years. It accounts for up to 2 million office visits annually among adolescents aged 15–19 years. A major risk factor is increased responsiveness of sebaceous glands and keratinocytes to androgenic hormones, particularly during puberty. Elevated androgen levels such as testosterone, dehydroepiandrosterone sulfate (DHEAS), or androstenedione may worsen acne severity, especially in women.
The pathophysiology involves inflammatory changes within sebaceous follicles, leading to accumulation of lipid-rich sebum and proliferation of Cutibacterium acnes (formerly Propionibacterium acnes), a Gram-positive anaerobic bacterium that normally exists in low numbers on the skin. Overgrowth of this organism within the follicle triggers inflammation, follicular rupture, and extension of inflammation into the surrounding dermis. This process results in the formation of papules, pustules, and nodules.
Clinically, patients present with open comedones (blackheads) or closed comedones (whiteheads). As inflammation progresses, lesions may become painful and form pustules or nodules. Scarring suggests more aggressive disease. Acne is classified as mild when primarily noninflammatory comedones are present, moderate when inflammatory papules and pustules affect larger skin areas, and severe when large painful nodules with potential scarring are present.
Treatment depends on severity. Mild to moderate acne often responds to topical therapy, including retinoids, benzoyl peroxide, and topical antimicrobials. Retinoids reduce sebaceous gland activity and normalize follicular keratinization. Benzoyl peroxide acts as a bactericidal agent and is often combined with topical antibiotics to reduce resistance. More severe cases may require oral antibiotics such as doxycycline, minocycline, tetracycline, trimethoprim-sulfamethoxazole, erythromycin, or clindamycin, although resistance has become increasingly common.
For severe nodulocystic acne or cases associated with scarring, oral isotretinoin is indicated. It reduces sebaceous gland size and sebum production, inhibits bacterial growth, and has anti-inflammatory properties. However, isotretinoin is highly teratogenic and may cause hypertriglyceridemia. Women of childbearing age must use two forms of contraception during treatment. Reports have also suggested possible associations with mood changes.
Additional therapies may include spironolactone or oral contraceptives in patients with hyperandrogenism. Intralesional corticosteroids can be used for severe inflammatory nodules. With appropriate treatment and adherence, most patients experience significant improvement, and early management helps reduce the risk of permanent scarring.
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Infectious Diseases and Microbiology: Vaginal Discharge / Vaginitis
Vaginal discharge may be physiologic or pathologic. Normal vaginal discharge, also referred to as leukorrhea, consists of cervical mucus and desquamated epithelial cells and is not associated with irritation, odor, or discomfort. In contrast, pathologic discharge is usually associated with infection and may present with abnormal color due to increased polymorphonuclear leukocytes, increased volume, malodor, vulvar pruritus, burning, dysuria, or dyspareunia. The three most common infectious causes of vaginitis are bacterial vaginosis, trichomoniasis, and candidiasis. Bacterial vaginosis represents a disruption of normal vaginal flora in which hydrogen-peroxide–producing lactobacilli are replaced by anaerobic organisms, mycoplasmas, and Gardnerella vaginalis.
Evaluation begins with a detailed history focusing on the characteristics of the discharge, associated symptoms, prior similar episodes, and a complete sexual history. Office-based diagnostic evaluation includes measurement of vaginal pH, performance of the amine (“whiff”) test by adding 10% potassium hydroxide to vaginal secretions, and microscopic examination of saline wet mount preparations to identify clue cells, motile trichomonads, and white blood cells. A potassium hydroxide preparation may reveal Candida pseudohyphae. In sexually active women, both endocervical and high vaginal swabs should be obtained. Chlamydial testing requires sampling of the squamocolumnar junction for culture or nucleic acid amplification testing. Screening cultures may include selective media for Neisseria gonorrhoeae, Candida species, and beta-hemolytic streptococci.
Bacterial vaginosis is the most common cause of vulvovaginal symptoms, followed by vulvovaginal candidiasis. Trichomoniasis is less common in developed countries. Risk factors for vaginal infections include unprotected sexual contact, multiple sexual partners, young age, and certain socioeconomic factors. Bacterial vaginosis is particularly associated with new or multiple sexual partners.
Clinically, vulvovaginal candidiasis often presents with vulvar pruritus and burning, dysuria at the urethral orifice, vaginal erythema, and occasionally thick, white, curd-like discharge. However, only a minority of patients exhibit the classic discharge. Trichomoniasis commonly presents with malodorous yellow discharge, vulvar erythema, itching, dysuria, urinary frequency, and dyspareunia, although symptoms are nonspecific. Bacterial vaginosis typically produces a thin, homogeneous discharge with a characteristic fishy odor that may be more noticeable after intercourse. In the absence of identifiable pathogens, vulvar inflammation may reflect noninfectious irritation or allergic reactions.
Diagnosis of trichomoniasis is commonly made by identifying motile organisms on saline wet mount, although sensitivity is moderate. Direct immunofluorescent testing and culture are more sensitive when available. Candidiasis is diagnosed by microscopic identification of budding yeast or pseudohyphae on saline or potassium hydroxide preparation. Vaginal pH in candidiasis is typically normal (≤4.5), and the amine test is negative. The presence of white blood cells without yeast or trichomonads suggests cervicitis. Absence of organisms on microscopy does not exclude infection, as culture or PCR may be required.
Treatment depends on the identified etiology. Trichomoniasis is treated with a single 2 g oral dose of metronidazole. Bacterial vaginosis is treated with oral metronidazole 500 mg twice daily for seven days or clindamycin 300 mg twice daily for seven days. Intravaginal metronidazole gel or clindamycin cream are effective alternatives. Symptomatic candidiasis is treated primarily with intravaginal azole antifungals such as clotrimazole, miconazole, butoconazole, or terconazole. Oral fluconazole as a single dose is an alternative but is more costly. In pregnancy, intravaginal azoles may be used after the first trimester.
Recurrent vulvovaginal candidiasis, defined as four or more episodes per year, may occur more frequently in women with diabetes mellitus or HIV infection. Vaginal trichomoniasis and bacterial vaginosis during pregnancy are associated with increased risk of preterm labor. Bacterial vaginosis is also associated with pelvic infections, postoperative endometritis, neonatal sepsis, increased risk of HIV acquisition and transmission, and increased susceptibility to other sexually transmitted infections.
Vaginal discharge may be physiologic or pathologic. Normal vaginal discharge, also referred to as leukorrhea, consists of cervical mucus and desquamated epithelial cells and is not associated with irritation, odor, or discomfort. In contrast, pathologic discharge is usually associated with infection and may present with abnormal color due to increased polymorphonuclear leukocytes, increased volume, malodor, vulvar pruritus, burning, dysuria, or dyspareunia. The three most common infectious causes of vaginitis are bacterial vaginosis, trichomoniasis, and candidiasis. Bacterial vaginosis represents a disruption of normal vaginal flora in which hydrogen-peroxide–producing lactobacilli are replaced by anaerobic organisms, mycoplasmas, and Gardnerella vaginalis.
Evaluation begins with a detailed history focusing on the characteristics of the discharge, associated symptoms, prior similar episodes, and a complete sexual history. Office-based diagnostic evaluation includes measurement of vaginal pH, performance of the amine (“whiff”) test by adding 10% potassium hydroxide to vaginal secretions, and microscopic examination of saline wet mount preparations to identify clue cells, motile trichomonads, and white blood cells. A potassium hydroxide preparation may reveal Candida pseudohyphae. In sexually active women, both endocervical and high vaginal swabs should be obtained. Chlamydial testing requires sampling of the squamocolumnar junction for culture or nucleic acid amplification testing. Screening cultures may include selective media for Neisseria gonorrhoeae, Candida species, and beta-hemolytic streptococci.
Bacterial vaginosis is the most common cause of vulvovaginal symptoms, followed by vulvovaginal candidiasis. Trichomoniasis is less common in developed countries. Risk factors for vaginal infections include unprotected sexual contact, multiple sexual partners, young age, and certain socioeconomic factors. Bacterial vaginosis is particularly associated with new or multiple sexual partners.
Clinically, vulvovaginal candidiasis often presents with vulvar pruritus and burning, dysuria at the urethral orifice, vaginal erythema, and occasionally thick, white, curd-like discharge. However, only a minority of patients exhibit the classic discharge. Trichomoniasis commonly presents with malodorous yellow discharge, vulvar erythema, itching, dysuria, urinary frequency, and dyspareunia, although symptoms are nonspecific. Bacterial vaginosis typically produces a thin, homogeneous discharge with a characteristic fishy odor that may be more noticeable after intercourse. In the absence of identifiable pathogens, vulvar inflammation may reflect noninfectious irritation or allergic reactions.
Diagnosis of trichomoniasis is commonly made by identifying motile organisms on saline wet mount, although sensitivity is moderate. Direct immunofluorescent testing and culture are more sensitive when available. Candidiasis is diagnosed by microscopic identification of budding yeast or pseudohyphae on saline or potassium hydroxide preparation. Vaginal pH in candidiasis is typically normal (≤4.5), and the amine test is negative. The presence of white blood cells without yeast or trichomonads suggests cervicitis. Absence of organisms on microscopy does not exclude infection, as culture or PCR may be required.
Treatment depends on the identified etiology. Trichomoniasis is treated with a single 2 g oral dose of metronidazole. Bacterial vaginosis is treated with oral metronidazole 500 mg twice daily for seven days or clindamycin 300 mg twice daily for seven days. Intravaginal metronidazole gel or clindamycin cream are effective alternatives. Symptomatic candidiasis is treated primarily with intravaginal azole antifungals such as clotrimazole, miconazole, butoconazole, or terconazole. Oral fluconazole as a single dose is an alternative but is more costly. In pregnancy, intravaginal azoles may be used after the first trimester.
Recurrent vulvovaginal candidiasis, defined as four or more episodes per year, may occur more frequently in women with diabetes mellitus or HIV infection. Vaginal trichomoniasis and bacterial vaginosis during pregnancy are associated with increased risk of preterm labor. Bacterial vaginosis is also associated with pelvic infections, postoperative endometritis, neonatal sepsis, increased risk of HIV acquisition and transmission, and increased susceptibility to other sexually transmitted infections.
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Infectious Diseases and Microbiology: Urethritis and Urethral Discharge
Basics
Description
Urethritis is inflammation of the urethra, often presenting with purulent or mucopurulent urethral discharge. In women, urethral syndrome or dysuria with sterile pyuria describes dysuria and urinary frequency with few or no bacteria detected in urine.
Approach to the Patient
Symptoms range from mild intermittent discomfort to persistent pain. History should include onset and duration of dysuria, associated symptoms, characteristics of discharge, and prior sexually transmitted infections. A complete genital examination is required. In men, palpate testes and spermatic cord to exclude epididymitis and evaluate for prostatitis; assess for cystitis in both sexes. To obtain discharge for examination, the urethra should be gently milked after the patient has avoided urination for several hours, ideally overnight.
Epidemiology
Urethritis is more common in men and represents one of the most frequently recognized sexually transmitted infections. Nongonococcal urethritis remains prevalent. Gonorrhea continues to affect adolescents and young adults disproportionately, particularly women aged 15–24 years. A substantial proportion of nongonococcal urethritis is caused by Chlamydia trachomatis. Antimicrobial resistance patterns, including quinolone-resistant Neisseria gonorrhoeae, have influenced treatment recommendations. Endourethral syphilitic chancre should also be considered in appropriate settings.
Risk Factors
Transmission risk depends on sexual exposure type. A high proportion of women exposed to men with urethral gonorrhea develop cervicitis, whereas fewer exposed men acquire infection from infected women. Incidence is highest among young, single individuals of lower socioeconomic and educational status.
General Prevention
Condom use reduces transmission of most sexually transmitted infections. Sexual partners of individuals with gonococcal or nongonococcal urethritis require evaluation and treatment to prevent reinfection and complications. Women with urinary symptoms without bacteriuria should be tested for N. gonorrhoeae. Patients diagnosed with urethritis should undergo screening for other sexually transmitted infections.
Etiology
Infectious causes include N. gonorrhoeae, C. trachomatis, Ureaplasma urealyticum, Mycoplasma genitalium, Trichomonas vaginalis, herpes simplex virus, and adenovirus. Noninfectious causes include Stevens–Johnson syndrome, granulomatosis with polyangiitis, chemical or mechanical irritation, and reactive arthritis (Reiter syndrome).
Diagnosis
Most men with urethral gonorrhea develop symptoms within days to two weeks after exposure, whereas nongonococcal urethritis typically has a 7–14 day incubation period. Dysuria is common in both conditions. Gonococcal discharge is usually purulent; nongonococcal discharge is less often purulent. Acute urethral syndrome presents with dysuria, urgency, and frequency.
Diagnostic Tests and Interpretation
Laboratory Studies
Gram-stained urethral smear showing five or more neutrophils per high-power field supports urethritis. Intracellular gram-negative diplococci confirm gonorrhea. Absence of diplococci suggests nongonococcal urethritis. Gram stain has high sensitivity for gonococcal infection in symptomatic men. First-void urine sediment may also demonstrate inflammatory cells. Nucleic acid amplification testing for N. gonorrhoeae and C. trachomatis is highly sensitive and specific and is recommended to guide patient and partner management. Candida has occasionally been implicated in urethritis when no other pathogen is identified.
Differential Diagnosis
Exclude systemic complications such as disseminated gonococcal infection or reactive arthritis. Consider bacterial prostatitis, cystitis, and in women, pyelonephritis if fever or flank pain is present. In sterile pyuria, evaluate for sexually transmitted pathogens such as C. trachomatis and N. gonorrhoeae, as well as other causes including tuberculosis or prostatitis.
Treatment
Medications
Gonococcal urethritis requires ceftriaxone in a single intramuscular dose, and most patients should also receive therapy targeting chlamydia. Nongonococcal urethritis is treated with doxycycline for seven days or a single dose of azithromycin. Alternative regimens include oral cephalosporins or spectinomycin where available. Fluoroquinolones are no longer recommended for gonorrhea due to resistance. Persistent or recurrent symptoms warrant reassessment for reinfection, treatment nonadherence, resistant strains, or coinfection such as T. vaginalis, which may require metronidazole. Recurrent nongonococcal urethritis may need prolonged therapy and evaluation for prostatic or structural abnormalities.
Ongoing Care and Follow-Up
Persistent hematuria after treatment requires urologic evaluation. Recurrence may reflect reinfection, coinfection, or treatment failure.
Complications
Chlamydia can cause salpingitis or bartholinitis and may result in neonatal conjunctivitis or pneumonia. Ureaplasma carriage has been associated with infertility. Both N. gonorrhoeae and C. trachomatis can cause acute epididymitis.
Basics
Description
Urethritis is inflammation of the urethra, often presenting with purulent or mucopurulent urethral discharge. In women, urethral syndrome or dysuria with sterile pyuria describes dysuria and urinary frequency with few or no bacteria detected in urine.
Approach to the Patient
Symptoms range from mild intermittent discomfort to persistent pain. History should include onset and duration of dysuria, associated symptoms, characteristics of discharge, and prior sexually transmitted infections. A complete genital examination is required. In men, palpate testes and spermatic cord to exclude epididymitis and evaluate for prostatitis; assess for cystitis in both sexes. To obtain discharge for examination, the urethra should be gently milked after the patient has avoided urination for several hours, ideally overnight.
Epidemiology
Urethritis is more common in men and represents one of the most frequently recognized sexually transmitted infections. Nongonococcal urethritis remains prevalent. Gonorrhea continues to affect adolescents and young adults disproportionately, particularly women aged 15–24 years. A substantial proportion of nongonococcal urethritis is caused by Chlamydia trachomatis. Antimicrobial resistance patterns, including quinolone-resistant Neisseria gonorrhoeae, have influenced treatment recommendations. Endourethral syphilitic chancre should also be considered in appropriate settings.
Risk Factors
Transmission risk depends on sexual exposure type. A high proportion of women exposed to men with urethral gonorrhea develop cervicitis, whereas fewer exposed men acquire infection from infected women. Incidence is highest among young, single individuals of lower socioeconomic and educational status.
General Prevention
Condom use reduces transmission of most sexually transmitted infections. Sexual partners of individuals with gonococcal or nongonococcal urethritis require evaluation and treatment to prevent reinfection and complications. Women with urinary symptoms without bacteriuria should be tested for N. gonorrhoeae. Patients diagnosed with urethritis should undergo screening for other sexually transmitted infections.
Etiology
Infectious causes include N. gonorrhoeae, C. trachomatis, Ureaplasma urealyticum, Mycoplasma genitalium, Trichomonas vaginalis, herpes simplex virus, and adenovirus. Noninfectious causes include Stevens–Johnson syndrome, granulomatosis with polyangiitis, chemical or mechanical irritation, and reactive arthritis (Reiter syndrome).
Diagnosis
Most men with urethral gonorrhea develop symptoms within days to two weeks after exposure, whereas nongonococcal urethritis typically has a 7–14 day incubation period. Dysuria is common in both conditions. Gonococcal discharge is usually purulent; nongonococcal discharge is less often purulent. Acute urethral syndrome presents with dysuria, urgency, and frequency.
Diagnostic Tests and Interpretation
Laboratory Studies
Gram-stained urethral smear showing five or more neutrophils per high-power field supports urethritis. Intracellular gram-negative diplococci confirm gonorrhea. Absence of diplococci suggests nongonococcal urethritis. Gram stain has high sensitivity for gonococcal infection in symptomatic men. First-void urine sediment may also demonstrate inflammatory cells. Nucleic acid amplification testing for N. gonorrhoeae and C. trachomatis is highly sensitive and specific and is recommended to guide patient and partner management. Candida has occasionally been implicated in urethritis when no other pathogen is identified.
Differential Diagnosis
Exclude systemic complications such as disseminated gonococcal infection or reactive arthritis. Consider bacterial prostatitis, cystitis, and in women, pyelonephritis if fever or flank pain is present. In sterile pyuria, evaluate for sexually transmitted pathogens such as C. trachomatis and N. gonorrhoeae, as well as other causes including tuberculosis or prostatitis.
Treatment
Medications
Gonococcal urethritis requires ceftriaxone in a single intramuscular dose, and most patients should also receive therapy targeting chlamydia. Nongonococcal urethritis is treated with doxycycline for seven days or a single dose of azithromycin. Alternative regimens include oral cephalosporins or spectinomycin where available. Fluoroquinolones are no longer recommended for gonorrhea due to resistance. Persistent or recurrent symptoms warrant reassessment for reinfection, treatment nonadherence, resistant strains, or coinfection such as T. vaginalis, which may require metronidazole. Recurrent nongonococcal urethritis may need prolonged therapy and evaluation for prostatic or structural abnormalities.
Ongoing Care and Follow-Up
Persistent hematuria after treatment requires urologic evaluation. Recurrence may reflect reinfection, coinfection, or treatment failure.
Complications
Chlamydia can cause salpingitis or bartholinitis and may result in neonatal conjunctivitis or pneumonia. Ureaplasma carriage has been associated with infertility. Both N. gonorrhoeae and C. trachomatis can cause acute epididymitis.
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Infectious Disease and Microbiology – Bacillary Angiomatosis / Peliosis Hepatica
Bacillary angiomatosis (BA) and peliosis hepatica (PH) are rare vascular proliferative infections caused by Bartonella species, most commonly affecting immunocompromised individuals, particularly those with advanced HIV infection and T-cell deficiency. Bacillary angiomatosis typically refers to the cutaneous or disseminated vascular form, whereas peliosis hepatica describes the visceral form involving blood-filled cystic lesions in the liver. If left untreated, the disease can be fatal.
This condition is globally distributed but uncommon. It is most frequently reported in individuals with HIV infection, particularly those with CD4 counts below 100 cells/mm³. Other risk factors include immunosuppression from transplantation or malignancy, poor sanitary conditions, homelessness, and close contact with cats. Bartonella henselae is most often associated with bacillary angiomatosis and cat exposure, while Bartonella quintana is linked to body louse infestation and is more commonly associated with bacteremia in homeless populations.
Preventive measures for immunocompromised individuals include careful handling of cats. Patients are advised to obtain healthy cats older than one year, practice strict hand hygiene after cleaning litter boxes, and avoid scratches or bites. Routine declawing or testing of cats is not recommended. Primary prophylaxis is generally not advised, although macrolides may offer protective effects against Bartonella infection. The need for lifelong suppressive therapy in HIV-infected patients has not been clearly established.
After an incubation period of at least one week, clinical manifestations can range from isolated bacteremia to extensive cutaneous, visceral, osseous, or central nervous system involvement. Constitutional symptoms such as fever, malaise, weight loss, and anemia are common. Peliosis hepatica often presents with persistent fever, abdominal pain, nausea, vomiting, and progressive hepatomegaly.
Cutaneous manifestations occur in the majority of patients with bacillary angiomatosis. Lesions are typically bright red, elevated papules that may vary from a few millimeters to several centimeters in size and may number from one to hundreds. Smaller lesions may have a thin overlying epidermis, while larger lesions may ulcerate or bleed easily and are often surrounded by a collarette. Subcutaneous nodules may develop without visible skin changes. Cellulitic plaque-like lesions may overlie deeper bone involvement. Extracutaneous manifestations include bone lesions, visceral involvement of the liver and spleen, lymphadenopathy, and, rarely, brain abscesses. Bone disease may present with pain alone or in association with overlying skin lesions. Peliosis hepatica is characterized by massive hepatomegaly and sometimes splenomegaly.
Diagnosis relies on tissue biopsy. Histologic examination using hematoxylin and eosin staining may show granular purple material representing organisms, while Warthin–Starry or Brown–Hopps staining can better visualize the bacteria. The organisms appear singly or in clusters. Culture is difficult and requires prolonged incubation (at least 21 days) using lysis-centrifugation techniques. Polymerase chain reaction (PCR) testing can aid in species identification. Serologic testing has limited sensitivity in immunocompromised patients. Laboratory findings may include mild elevation of transaminases, marked elevation of alkaline phosphatase, and mild-to-moderate pancytopenia in visceral disease.
Imaging findings depend on organ involvement. Bone radiographs may reveal well-circumscribed lytic lesions or cortical destruction with aggressive periosteal reaction. CT scans may demonstrate hepatosplenomegaly and abdominal lymphadenopathy, with heterogeneous liver parenchyma. Liver biopsy in peliosis hepatica shows dilated, blood-filled cystic spaces within the hepatic parenchyma, often with associated necrosis in advanced cases.
The differential diagnosis includes Kaposi’s sarcoma, pyogenic granulomas, angiomas, and other vascular tumors. Kaposi’s sarcoma may coexist with bacillary angiomatosis and should be considered, particularly if lesions fail to improve with antibiotic therapy.
Treatment begins with evaluation of the extent of organ involvement. First-line therapy consists of erythromycin 500 mg orally every six hours or doxycycline 100 mg orally twice daily. Treatment duration is generally three months for bacillary angiomatosis and four months for peliosis hepatica, with longer courses required in immunocompromised patients. A Jarisch–Herxheimer reaction may occur after initiation of therapy; pretreatment with antipyretics for the first 72 hours may help.
For patients intolerant to first-line therapy, azithromycin or clarithromycin may be used. In severe, life-threatening, or central nervous system disease—particularly in immunocompromised individuals—combination therapy with rifampin added to erythromycin or doxycycline is recommended. TMP-SMX and ciprofloxacin have shown inconsistent results. Most patients can be managed as outpatients, though hospitalization and intravenous therapy are necessary for extensive or fulminant disease.
Clinical improvement is often observed within 4–7 days of therapy, with near-complete resolution of lesions by 3–4 weeks. Relapses occur in approximately 15% of cases and may require prolonged suppressive therapy. Monitoring includes clinical assessment, serial liver function tests in visceral disease, and imaging studies for bone involvement.
Complications of visceral disease include anemia, pancytopenia due to hypersplenism, and splenic rupture with hemoperitoneum. Early recognition and prolonged antimicrobial therapy are essential for favorable outcomes.
Bacillary angiomatosis (BA) and peliosis hepatica (PH) are rare vascular proliferative infections caused by Bartonella species, most commonly affecting immunocompromised individuals, particularly those with advanced HIV infection and T-cell deficiency. Bacillary angiomatosis typically refers to the cutaneous or disseminated vascular form, whereas peliosis hepatica describes the visceral form involving blood-filled cystic lesions in the liver. If left untreated, the disease can be fatal.
This condition is globally distributed but uncommon. It is most frequently reported in individuals with HIV infection, particularly those with CD4 counts below 100 cells/mm³. Other risk factors include immunosuppression from transplantation or malignancy, poor sanitary conditions, homelessness, and close contact with cats. Bartonella henselae is most often associated with bacillary angiomatosis and cat exposure, while Bartonella quintana is linked to body louse infestation and is more commonly associated with bacteremia in homeless populations.
Preventive measures for immunocompromised individuals include careful handling of cats. Patients are advised to obtain healthy cats older than one year, practice strict hand hygiene after cleaning litter boxes, and avoid scratches or bites. Routine declawing or testing of cats is not recommended. Primary prophylaxis is generally not advised, although macrolides may offer protective effects against Bartonella infection. The need for lifelong suppressive therapy in HIV-infected patients has not been clearly established.
After an incubation period of at least one week, clinical manifestations can range from isolated bacteremia to extensive cutaneous, visceral, osseous, or central nervous system involvement. Constitutional symptoms such as fever, malaise, weight loss, and anemia are common. Peliosis hepatica often presents with persistent fever, abdominal pain, nausea, vomiting, and progressive hepatomegaly.
Cutaneous manifestations occur in the majority of patients with bacillary angiomatosis. Lesions are typically bright red, elevated papules that may vary from a few millimeters to several centimeters in size and may number from one to hundreds. Smaller lesions may have a thin overlying epidermis, while larger lesions may ulcerate or bleed easily and are often surrounded by a collarette. Subcutaneous nodules may develop without visible skin changes. Cellulitic plaque-like lesions may overlie deeper bone involvement. Extracutaneous manifestations include bone lesions, visceral involvement of the liver and spleen, lymphadenopathy, and, rarely, brain abscesses. Bone disease may present with pain alone or in association with overlying skin lesions. Peliosis hepatica is characterized by massive hepatomegaly and sometimes splenomegaly.
Diagnosis relies on tissue biopsy. Histologic examination using hematoxylin and eosin staining may show granular purple material representing organisms, while Warthin–Starry or Brown–Hopps staining can better visualize the bacteria. The organisms appear singly or in clusters. Culture is difficult and requires prolonged incubation (at least 21 days) using lysis-centrifugation techniques. Polymerase chain reaction (PCR) testing can aid in species identification. Serologic testing has limited sensitivity in immunocompromised patients. Laboratory findings may include mild elevation of transaminases, marked elevation of alkaline phosphatase, and mild-to-moderate pancytopenia in visceral disease.
Imaging findings depend on organ involvement. Bone radiographs may reveal well-circumscribed lytic lesions or cortical destruction with aggressive periosteal reaction. CT scans may demonstrate hepatosplenomegaly and abdominal lymphadenopathy, with heterogeneous liver parenchyma. Liver biopsy in peliosis hepatica shows dilated, blood-filled cystic spaces within the hepatic parenchyma, often with associated necrosis in advanced cases.
The differential diagnosis includes Kaposi’s sarcoma, pyogenic granulomas, angiomas, and other vascular tumors. Kaposi’s sarcoma may coexist with bacillary angiomatosis and should be considered, particularly if lesions fail to improve with antibiotic therapy.
Treatment begins with evaluation of the extent of organ involvement. First-line therapy consists of erythromycin 500 mg orally every six hours or doxycycline 100 mg orally twice daily. Treatment duration is generally three months for bacillary angiomatosis and four months for peliosis hepatica, with longer courses required in immunocompromised patients. A Jarisch–Herxheimer reaction may occur after initiation of therapy; pretreatment with antipyretics for the first 72 hours may help.
For patients intolerant to first-line therapy, azithromycin or clarithromycin may be used. In severe, life-threatening, or central nervous system disease—particularly in immunocompromised individuals—combination therapy with rifampin added to erythromycin or doxycycline is recommended. TMP-SMX and ciprofloxacin have shown inconsistent results. Most patients can be managed as outpatients, though hospitalization and intravenous therapy are necessary for extensive or fulminant disease.
Clinical improvement is often observed within 4–7 days of therapy, with near-complete resolution of lesions by 3–4 weeks. Relapses occur in approximately 15% of cases and may require prolonged suppressive therapy. Monitoring includes clinical assessment, serial liver function tests in visceral disease, and imaging studies for bone involvement.
Complications of visceral disease include anemia, pancytopenia due to hypersplenism, and splenic rupture with hemoperitoneum. Early recognition and prolonged antimicrobial therapy are essential for favorable outcomes.
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Infectious Disease and Microbiology – Babesiosis
Babesiosis is a protozoal infection caused by Babesia species, intraerythrocytic parasites with a predilection for human red blood cells. It is an important cause of hemolytic disease in endemic regions. The most common species in the United States is Babesia microti, transmitted primarily through the bite of Ixodes (deer) ticks. Less common modes of transmission include blood transfusion and, rarely, congenital (maternal–fetal) transmission. Most cases in the United States occur in the Northeastern and Midwestern regions, while other species such as Babesia divergens (Europe) and Babesia duncani (Western US) are also recognized.
Babesiosis is considered an emerging infectious disease, with increasing reported cases over recent decades. Expansion of deer populations, increased tick density, and greater human exposure to endemic areas contribute to rising incidence. Many infections, especially in younger and immunocompetent individuals, are asymptomatic, leading to underestimation of true prevalence. Serologic surveys in highly endemic areas show that 0.5–15% of blood donors have evidence of prior exposure.
Risk factors include residence in or travel to endemic areas, asplenia, and immunosuppression (e.g., HIV infection or chemotherapy). Preventive strategies focus on avoiding tick exposure, especially during peak transmission months (May through October). Use of insect repellents containing DEET, treatment of clothing with permethrin, daily tick checks after outdoor activity, prompt tick removal (within 24 hours), and examination of pets are recommended. Asplenic and immunocompromised individuals should exercise particular caution in endemic regions.
The life cycle of Babesia involves transmission between Ixodes ticks and vertebrate hosts, primarily white-footed mice. Humans are incidental, “dead-end” hosts and do not contribute to further transmission. After a tick bite, sporozoites enter the bloodstream and invade erythrocytes, where they develop into trophozoites. These replicate asexually to form 2–4 merozoites, which lyse red blood cells and infect additional erythrocytes, resulting in hemolysis and anemia.
Clinical presentation ranges from asymptomatic infection to severe, life-threatening disease. Common symptoms include fever, chills, weakness, headache, nausea, abdominal pain, myalgias, and dark urine. Severe cases may present with shortness of breath or chest pain. A detailed history should include recent travel to endemic areas, tick exposure, outdoor activities, pets, prior Lyme disease, or recent transfusions. Co-infection with Lyme disease or human granulocytic anaplasmosis is common because these infections share the same vector.
On physical examination, patients may have fever, pallor, jaundice, splenomegaly, and hepatomegaly. Lymphadenopathy is typically absent. In cases of Lyme co-infection, erythema migrans rash may be present.
Laboratory findings include anemia and thrombocytopenia on complete blood count, along with laboratory evidence of hemolysis such as elevated reticulocyte count, lactate dehydrogenase (LDH), and indirect bilirubin, and low haptoglobin. Thin peripheral blood smears are the cornerstone of diagnosis and may show intraerythrocytic parasites. Multiple smears over several days may be required in low parasitemia. The characteristic “Maltese cross” tetrad formation is occasionally seen and is pathognomonic when present. Unlike malaria, Babesia organisms may be observed extracellularly in heavy infection. If smears are negative but suspicion remains high, PCR testing for Babesia DNA is recommended. Serologic testing using indirect immunofluorescent antibody assays can support the diagnosis in selected cases. Imaging is usually unnecessary but may confirm splenomegaly or hepatomegaly.
Treatment for uncomplicated B. microti infection consists of oral atovaquone plus azithromycin for 7–10 days. Severe cases, including those with high parasitemia or significant symptoms, are treated with quinine plus clindamycin, administered orally or intravenously. Immunocompromised patients or those with high parasite burdens may require prolonged therapy for at least six weeks, including two weeks after clearance of parasites from blood smears. Asymptomatic immunocompetent individuals with low-level parasitemia for less than three months typically do not require treatment. In severe disease with parasitemia greater than 10% or with complications such as shock or acute respiratory distress syndrome, red blood cell exchange transfusion may be indicated.
Hospitalized patients require daily monitoring of complete blood count and peripheral blood smears to assess hemolysis and parasite burden. Patients should be educated about preventive measures to reduce the risk of reinfection.
Complications of babesiosis include disseminated intravascular coagulation, severe hemolytic anemia, congestive heart failure, acute respiratory distress syndrome, renal dysfunction, and hypotension. Severe disease is more likely in asplenic and immunocompromised individuals.
Babesiosis is a protozoal infection caused by Babesia species, intraerythrocytic parasites with a predilection for human red blood cells. It is an important cause of hemolytic disease in endemic regions. The most common species in the United States is Babesia microti, transmitted primarily through the bite of Ixodes (deer) ticks. Less common modes of transmission include blood transfusion and, rarely, congenital (maternal–fetal) transmission. Most cases in the United States occur in the Northeastern and Midwestern regions, while other species such as Babesia divergens (Europe) and Babesia duncani (Western US) are also recognized.
Babesiosis is considered an emerging infectious disease, with increasing reported cases over recent decades. Expansion of deer populations, increased tick density, and greater human exposure to endemic areas contribute to rising incidence. Many infections, especially in younger and immunocompetent individuals, are asymptomatic, leading to underestimation of true prevalence. Serologic surveys in highly endemic areas show that 0.5–15% of blood donors have evidence of prior exposure.
Risk factors include residence in or travel to endemic areas, asplenia, and immunosuppression (e.g., HIV infection or chemotherapy). Preventive strategies focus on avoiding tick exposure, especially during peak transmission months (May through October). Use of insect repellents containing DEET, treatment of clothing with permethrin, daily tick checks after outdoor activity, prompt tick removal (within 24 hours), and examination of pets are recommended. Asplenic and immunocompromised individuals should exercise particular caution in endemic regions.
The life cycle of Babesia involves transmission between Ixodes ticks and vertebrate hosts, primarily white-footed mice. Humans are incidental, “dead-end” hosts and do not contribute to further transmission. After a tick bite, sporozoites enter the bloodstream and invade erythrocytes, where they develop into trophozoites. These replicate asexually to form 2–4 merozoites, which lyse red blood cells and infect additional erythrocytes, resulting in hemolysis and anemia.
Clinical presentation ranges from asymptomatic infection to severe, life-threatening disease. Common symptoms include fever, chills, weakness, headache, nausea, abdominal pain, myalgias, and dark urine. Severe cases may present with shortness of breath or chest pain. A detailed history should include recent travel to endemic areas, tick exposure, outdoor activities, pets, prior Lyme disease, or recent transfusions. Co-infection with Lyme disease or human granulocytic anaplasmosis is common because these infections share the same vector.
On physical examination, patients may have fever, pallor, jaundice, splenomegaly, and hepatomegaly. Lymphadenopathy is typically absent. In cases of Lyme co-infection, erythema migrans rash may be present.
Laboratory findings include anemia and thrombocytopenia on complete blood count, along with laboratory evidence of hemolysis such as elevated reticulocyte count, lactate dehydrogenase (LDH), and indirect bilirubin, and low haptoglobin. Thin peripheral blood smears are the cornerstone of diagnosis and may show intraerythrocytic parasites. Multiple smears over several days may be required in low parasitemia. The characteristic “Maltese cross” tetrad formation is occasionally seen and is pathognomonic when present. Unlike malaria, Babesia organisms may be observed extracellularly in heavy infection. If smears are negative but suspicion remains high, PCR testing for Babesia DNA is recommended. Serologic testing using indirect immunofluorescent antibody assays can support the diagnosis in selected cases. Imaging is usually unnecessary but may confirm splenomegaly or hepatomegaly.
Treatment for uncomplicated B. microti infection consists of oral atovaquone plus azithromycin for 7–10 days. Severe cases, including those with high parasitemia or significant symptoms, are treated with quinine plus clindamycin, administered orally or intravenously. Immunocompromised patients or those with high parasite burdens may require prolonged therapy for at least six weeks, including two weeks after clearance of parasites from blood smears. Asymptomatic immunocompetent individuals with low-level parasitemia for less than three months typically do not require treatment. In severe disease with parasitemia greater than 10% or with complications such as shock or acute respiratory distress syndrome, red blood cell exchange transfusion may be indicated.
Hospitalized patients require daily monitoring of complete blood count and peripheral blood smears to assess hemolysis and parasite burden. Patients should be educated about preventive measures to reduce the risk of reinfection.
Complications of babesiosis include disseminated intravascular coagulation, severe hemolytic anemia, congestive heart failure, acute respiratory distress syndrome, renal dysfunction, and hypotension. Severe disease is more likely in asplenic and immunocompromised individuals.
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Infectious Disease and Microbiology – Atypical Mycobacteria (Nontuberculous Mycobacteria)
Atypical mycobacteria refer to infections caused by nontuberculous mycobacteria (NTM), a diverse group of environmental mycobacterial species distinct from Mycobacterium tuberculosis. In children, atypical mycobacteria should be considered in cases of unilateral cervical lymphadenitis, particularly in those aged 1–5 years. The swelling typically involves the anterior cervical chain, enlarges gradually, and may form fistulas through the skin. Enlarged lymph nodes are often painless, and systemic symptoms are uncommon. Most pediatric cases are caused by Mycobacterium avium complex (MAC), while M. scrofulaceum and M. tuberculosis are less frequent causes. Approximately 300 cases of MAC lymphadenitis occur annually in the United States. Overall prevalence ranges from 1 to 7.2 cases per 100,000 persons in the US, varying by region, and about half of NTM isolates represent true pathogens.
Risk factors for NTM infection include advanced age, immunosuppression, HIV infection with low CD4 counts, interferon-gamma deficiencies, and underlying structural lung disease such as bronchiectasis or chronic obstructive pulmonary disease. Genetic defects such as IFN-γ receptor 1 (IFNγR1) or interleukin-12 receptor β1 (IL-12βR1) deficiency predispose individuals to disseminated disease. In patients with AIDS and CD4 counts below 100 cells/mm³, primary prophylaxis with weekly azithromycin 1200 mg is recommended; alternatives include clarithromycin or rifabutin.
NTM are widely found in soil and water, including hot tubs and tap water. Human-to-human transmission has not been documented. Infection occurs primarily through ingestion or inhalation rather than reactivation of latent disease. Granuloma formation results from interactions between macrophages, lymphocytes, and natural killer cells. Disseminated infection arises from uncontrolled localized disease, especially in immunocompromised hosts. These organisms are aerobic, non–spore-forming bacilli with mycolic acid–containing cell walls. They are categorized by growth rate into rapid-growing mycobacteria (e.g., M. fortuitum, M. chelonae/abscessus, M. smegmatis), intermediate growers (e.g., M. marinum, M. gordonae), and slow-growing organisms (e.g., MAC, M. kansasii, M. xenopi, M. scrofulaceum, M. haemophilum, M. ulcerans).
Clinical syndromes include pulmonary disease, lymphadenitis, skin and soft tissue infection, osteoarticular disease, catheter-related infection, and disseminated disease. Pulmonary infection typically presents with chronic productive cough and may progress to weight loss, fatigue, dyspnea, hemoptysis, and chest pain. Soft tissue infections often follow trauma, surgery, or aquatic exposure and appear as papular or ulcerative lesions that may spread along lymphatics. Lymphadenitis usually manifests as painless or mildly tender enlargement of submandibular or jugular lymph nodes. Disseminated disease, most commonly seen in advanced HIV infection, presents with fever, fatigue, anorexia, and laboratory abnormalities such as pancytopenia or elevated alkaline phosphatase.
Diagnosis requires correlation of clinical, radiographic, and microbiologic findings because NTM may represent colonization rather than true infection. In pulmonary disease, chest imaging may show upper-lobe cavitary lesions, nodular or reticulonodular infiltrates, or adenopathy. Cavitary disease is common in MAC pulmonary infections and typically involves thin-walled cavities measuring 2–4 cm. At least three sputum samples (or bronchoalveolar lavage specimens) should be obtained for acid-fast bacillus smear and culture. Mycobacterial blood cultures are positive in approximately 90% of disseminated MAC cases. Tissue biopsy demonstrating granulomas with giant cells and acid-fast bacilli supports localized infection, whereas well-formed granulomas may be absent in disseminated disease. Definitive identification and susceptibility testing should be performed at specialized laboratories.
Treatment depends on the species and site of infection and often requires prolonged multidrug therapy. Pulmonary MAC is treated with rifampin, ethambutol, and a macrolide (azithromycin or clarithromycin), sometimes with an aminoglycoside for severe disease. Therapy continues for at least 12 months after cultures become negative. Pulmonary infection with M. kansasii is treated with isoniazid, rifampin, and ethambutol. Rapid-growing mycobacteria causing soft tissue infections are treated with two active agents based on susceptibility testing, such as trimethoprim–sulfamethoxazole, doxycycline, levofloxacin, or clarithromycin. Severe M. abscessus infections may require amikacin combined with clarithromycin and cefoxitin or imipenem. Disseminated MAC in HIV patients is treated with a macrolide plus ethambutol, with consideration of adding rifampin.
Surgical management may be necessary in selected cases. Resection of affected lymph nodes in MAC lymphadenitis achieves cure in approximately 90% of pediatric cases without antimicrobials. Lung resection may be considered in localized refractory pulmonary disease. Incision and drainage are often required for soft tissue infections.
Long-term follow-up is essential because therapy may last months to years and drug toxicities are common. Patients require regular laboratory monitoring, evaluation for drug–drug interactions, and sometimes therapeutic drug monitoring. Prognosis depends on the infecting species, the site of disease, and the host’s immune status. Complications include ulceration and fistula formation in lymphadenitis and, rarely, gastrointestinal complications such as intussusception or obstruction in disseminated MAC.
Atypical mycobacteria refer to infections caused by nontuberculous mycobacteria (NTM), a diverse group of environmental mycobacterial species distinct from Mycobacterium tuberculosis. In children, atypical mycobacteria should be considered in cases of unilateral cervical lymphadenitis, particularly in those aged 1–5 years. The swelling typically involves the anterior cervical chain, enlarges gradually, and may form fistulas through the skin. Enlarged lymph nodes are often painless, and systemic symptoms are uncommon. Most pediatric cases are caused by Mycobacterium avium complex (MAC), while M. scrofulaceum and M. tuberculosis are less frequent causes. Approximately 300 cases of MAC lymphadenitis occur annually in the United States. Overall prevalence ranges from 1 to 7.2 cases per 100,000 persons in the US, varying by region, and about half of NTM isolates represent true pathogens.
Risk factors for NTM infection include advanced age, immunosuppression, HIV infection with low CD4 counts, interferon-gamma deficiencies, and underlying structural lung disease such as bronchiectasis or chronic obstructive pulmonary disease. Genetic defects such as IFN-γ receptor 1 (IFNγR1) or interleukin-12 receptor β1 (IL-12βR1) deficiency predispose individuals to disseminated disease. In patients with AIDS and CD4 counts below 100 cells/mm³, primary prophylaxis with weekly azithromycin 1200 mg is recommended; alternatives include clarithromycin or rifabutin.
NTM are widely found in soil and water, including hot tubs and tap water. Human-to-human transmission has not been documented. Infection occurs primarily through ingestion or inhalation rather than reactivation of latent disease. Granuloma formation results from interactions between macrophages, lymphocytes, and natural killer cells. Disseminated infection arises from uncontrolled localized disease, especially in immunocompromised hosts. These organisms are aerobic, non–spore-forming bacilli with mycolic acid–containing cell walls. They are categorized by growth rate into rapid-growing mycobacteria (e.g., M. fortuitum, M. chelonae/abscessus, M. smegmatis), intermediate growers (e.g., M. marinum, M. gordonae), and slow-growing organisms (e.g., MAC, M. kansasii, M. xenopi, M. scrofulaceum, M. haemophilum, M. ulcerans).
Clinical syndromes include pulmonary disease, lymphadenitis, skin and soft tissue infection, osteoarticular disease, catheter-related infection, and disseminated disease. Pulmonary infection typically presents with chronic productive cough and may progress to weight loss, fatigue, dyspnea, hemoptysis, and chest pain. Soft tissue infections often follow trauma, surgery, or aquatic exposure and appear as papular or ulcerative lesions that may spread along lymphatics. Lymphadenitis usually manifests as painless or mildly tender enlargement of submandibular or jugular lymph nodes. Disseminated disease, most commonly seen in advanced HIV infection, presents with fever, fatigue, anorexia, and laboratory abnormalities such as pancytopenia or elevated alkaline phosphatase.
Diagnosis requires correlation of clinical, radiographic, and microbiologic findings because NTM may represent colonization rather than true infection. In pulmonary disease, chest imaging may show upper-lobe cavitary lesions, nodular or reticulonodular infiltrates, or adenopathy. Cavitary disease is common in MAC pulmonary infections and typically involves thin-walled cavities measuring 2–4 cm. At least three sputum samples (or bronchoalveolar lavage specimens) should be obtained for acid-fast bacillus smear and culture. Mycobacterial blood cultures are positive in approximately 90% of disseminated MAC cases. Tissue biopsy demonstrating granulomas with giant cells and acid-fast bacilli supports localized infection, whereas well-formed granulomas may be absent in disseminated disease. Definitive identification and susceptibility testing should be performed at specialized laboratories.
Treatment depends on the species and site of infection and often requires prolonged multidrug therapy. Pulmonary MAC is treated with rifampin, ethambutol, and a macrolide (azithromycin or clarithromycin), sometimes with an aminoglycoside for severe disease. Therapy continues for at least 12 months after cultures become negative. Pulmonary infection with M. kansasii is treated with isoniazid, rifampin, and ethambutol. Rapid-growing mycobacteria causing soft tissue infections are treated with two active agents based on susceptibility testing, such as trimethoprim–sulfamethoxazole, doxycycline, levofloxacin, or clarithromycin. Severe M. abscessus infections may require amikacin combined with clarithromycin and cefoxitin or imipenem. Disseminated MAC in HIV patients is treated with a macrolide plus ethambutol, with consideration of adding rifampin.
Surgical management may be necessary in selected cases. Resection of affected lymph nodes in MAC lymphadenitis achieves cure in approximately 90% of pediatric cases without antimicrobials. Lung resection may be considered in localized refractory pulmonary disease. Incision and drainage are often required for soft tissue infections.
Long-term follow-up is essential because therapy may last months to years and drug toxicities are common. Patients require regular laboratory monitoring, evaluation for drug–drug interactions, and sometimes therapeutic drug monitoring. Prognosis depends on the infecting species, the site of disease, and the host’s immune status. Complications include ulceration and fistula formation in lymphadenitis and, rarely, gastrointestinal complications such as intussusception or obstruction in disseminated MAC.
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Infectious Disease and Microbiology – Aspergillosis
Aspergillosis describes a spectrum of illnesses caused by species of Aspergillus, ranging from simple colonization or allergic reactions to localized or disseminated invasive disease. Although virtually any organ may be involved, the lungs are most commonly affected, followed by the paranasal sinuses and, less frequently, the central nervous system.
The number of Aspergillus species implicated in human disease continues to expand. Aspergillus fumigatus remains the most common cause of invasive infection, but A. flavus, A. terreus, A. niger, and A. versicolor are increasingly recognized. Invasive aspergillosis is second only to candidiasis among invasive fungal infections in immunocompromised patients. Major risk factors include granulocytopenia (the most significant), hematopoietic stem cell transplantation, solid-organ transplantation, acute leukemia, prolonged corticosteroid or cytotoxic therapy, chronic obstructive pulmonary disease treated with steroids, prolonged antibiotic use, liver failure, diabetes mellitus, chronic granulomatous disease, and advanced AIDS (CD4 count ≤50 cells/mm³). Genetic polymorphisms in Toll-like receptors 4 and 9 may influence susceptibility to invasive aspergillosis and allergic bronchopulmonary aspergillosis (ABPA), respectively.
Preventive strategies focus on environmental control, particularly during hospital construction activities, to reduce exposure to airborne conidia. High-efficiency particulate air (HEPA) filtration systems are recommended for high-risk patients. In selected individuals with prior invasive disease who may become neutropenic, antifungal prophylaxis with agents such as voriconazole or amphotericin B may be considered.
Pathophysiologically, inhaled conidia are small enough to reach the alveoli. In immunocompetent hosts, alveolar macrophages clear the spores. In immunocompromised individuals, impaired macrophage function allows germination into hyphae, triggering inflammatory cytokine release, vascular invasion, tissue necrosis, and possible hematogenous dissemination. In ABPA, colonization in atopic individuals activates TH2 CD4+ T cells, driving IgE production and eosinophilia, exacerbating asthma and potentially leading to bronchiectasis. Chronic pulmonary aspergillosis, including aspergilloma formation, often develops in patients with prior lung disease such as tuberculosis, lung cancer resection, ABPA, or bullous disease.
Clinical manifestations vary by syndrome. ABPA occurs in patients with asthma or cystic fibrosis and presents with worsening respiratory symptoms, malaise, and occasionally hemoptysis. Chronic pulmonary aspergillosis typically presents with weight loss, chronic cough, hemoptysis, dyspnea, and constitutional symptoms. Invasive aspergillosis commonly presents with fever, pleuritic chest pain, cough, dyspnea, and hemoptysis, especially in neutropenic or otherwise immunocompromised hosts.
Diagnosis depends on clinical suspicion and supportive laboratory and imaging findings. In ABPA, chest imaging may show upper-lobe infiltrates, bronchial wall thickening, bronchiectasis, or ground-glass opacities. Peripheral eosinophilia, elevated total serum IgE, positive immediate skin test to Aspergillus, and elevated serum IgG to A. fumigatus support the diagnosis. Chronic pulmonary aspergillosis is characterized radiographically by one or more lung cavities, sometimes containing a mobile aspergilloma with an air-crescent sign. Invasive aspergillosis requires demonstration of fungal invasion on tissue biopsy for definitive diagnosis. Serum galactomannan and β-glucan assays are useful adjunctive tests, particularly in high-risk patients.
Treatment depends on disease type. ABPA is managed with systemic glucocorticoids combined with itraconazole, with steroids tapered over several months when possible. Chronic pulmonary aspergillosis often requires long-term antifungal therapy, commonly with voriconazole, and in selected cases surgical resection of aspergilloma. Embolization may be used to control hemoptysis. Invasive aspergillosis is treated with voriconazole as first-line therapy. Alternatives include amphotericin B, itraconazole, or echinocandins, although combination therapy remains of uncertain benefit. Surgical debridement is recommended when feasible.
Patients with invasive disease require prompt initiation of antifungal therapy and stabilization of hemodynamic parameters. Hospital admission is warranted for unstable patients, those with significant hemoptysis, or immunocompromised individuals with fever. Long-term monitoring is essential to detect relapse, progression, or drug toxicity. Therapeutic drug monitoring of voriconazole trough levels is recommended during prolonged therapy.
Prognosis depends largely on the degree of immunosuppression and fungal burden. Complications include massive hemoptysis in chronic disease, pulmonary fibrosis and bronchiectasis in ABPA, pneumothorax, empyema, and disseminated infection in invasive disease. Central nervous system involvement may result in vascular occlusion and severe neurologic sequelae. Early recognition and aggressive management are critical to improving outcomes.
Aspergillosis describes a spectrum of illnesses caused by species of Aspergillus, ranging from simple colonization or allergic reactions to localized or disseminated invasive disease. Although virtually any organ may be involved, the lungs are most commonly affected, followed by the paranasal sinuses and, less frequently, the central nervous system.
The number of Aspergillus species implicated in human disease continues to expand. Aspergillus fumigatus remains the most common cause of invasive infection, but A. flavus, A. terreus, A. niger, and A. versicolor are increasingly recognized. Invasive aspergillosis is second only to candidiasis among invasive fungal infections in immunocompromised patients. Major risk factors include granulocytopenia (the most significant), hematopoietic stem cell transplantation, solid-organ transplantation, acute leukemia, prolonged corticosteroid or cytotoxic therapy, chronic obstructive pulmonary disease treated with steroids, prolonged antibiotic use, liver failure, diabetes mellitus, chronic granulomatous disease, and advanced AIDS (CD4 count ≤50 cells/mm³). Genetic polymorphisms in Toll-like receptors 4 and 9 may influence susceptibility to invasive aspergillosis and allergic bronchopulmonary aspergillosis (ABPA), respectively.
Preventive strategies focus on environmental control, particularly during hospital construction activities, to reduce exposure to airborne conidia. High-efficiency particulate air (HEPA) filtration systems are recommended for high-risk patients. In selected individuals with prior invasive disease who may become neutropenic, antifungal prophylaxis with agents such as voriconazole or amphotericin B may be considered.
Pathophysiologically, inhaled conidia are small enough to reach the alveoli. In immunocompetent hosts, alveolar macrophages clear the spores. In immunocompromised individuals, impaired macrophage function allows germination into hyphae, triggering inflammatory cytokine release, vascular invasion, tissue necrosis, and possible hematogenous dissemination. In ABPA, colonization in atopic individuals activates TH2 CD4+ T cells, driving IgE production and eosinophilia, exacerbating asthma and potentially leading to bronchiectasis. Chronic pulmonary aspergillosis, including aspergilloma formation, often develops in patients with prior lung disease such as tuberculosis, lung cancer resection, ABPA, or bullous disease.
Clinical manifestations vary by syndrome. ABPA occurs in patients with asthma or cystic fibrosis and presents with worsening respiratory symptoms, malaise, and occasionally hemoptysis. Chronic pulmonary aspergillosis typically presents with weight loss, chronic cough, hemoptysis, dyspnea, and constitutional symptoms. Invasive aspergillosis commonly presents with fever, pleuritic chest pain, cough, dyspnea, and hemoptysis, especially in neutropenic or otherwise immunocompromised hosts.
Diagnosis depends on clinical suspicion and supportive laboratory and imaging findings. In ABPA, chest imaging may show upper-lobe infiltrates, bronchial wall thickening, bronchiectasis, or ground-glass opacities. Peripheral eosinophilia, elevated total serum IgE, positive immediate skin test to Aspergillus, and elevated serum IgG to A. fumigatus support the diagnosis. Chronic pulmonary aspergillosis is characterized radiographically by one or more lung cavities, sometimes containing a mobile aspergilloma with an air-crescent sign. Invasive aspergillosis requires demonstration of fungal invasion on tissue biopsy for definitive diagnosis. Serum galactomannan and β-glucan assays are useful adjunctive tests, particularly in high-risk patients.
Treatment depends on disease type. ABPA is managed with systemic glucocorticoids combined with itraconazole, with steroids tapered over several months when possible. Chronic pulmonary aspergillosis often requires long-term antifungal therapy, commonly with voriconazole, and in selected cases surgical resection of aspergilloma. Embolization may be used to control hemoptysis. Invasive aspergillosis is treated with voriconazole as first-line therapy. Alternatives include amphotericin B, itraconazole, or echinocandins, although combination therapy remains of uncertain benefit. Surgical debridement is recommended when feasible.
Patients with invasive disease require prompt initiation of antifungal therapy and stabilization of hemodynamic parameters. Hospital admission is warranted for unstable patients, those with significant hemoptysis, or immunocompromised individuals with fever. Long-term monitoring is essential to detect relapse, progression, or drug toxicity. Therapeutic drug monitoring of voriconazole trough levels is recommended during prolonged therapy.
Prognosis depends largely on the degree of immunosuppression and fungal burden. Complications include massive hemoptysis in chronic disease, pulmonary fibrosis and bronchiectasis in ABPA, pneumothorax, empyema, and disseminated infection in invasive disease. Central nervous system involvement may result in vascular occlusion and severe neurologic sequelae. Early recognition and aggressive management are critical to improving outcomes.
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Infectious Disease and Microbiology – Appendicitis
Appendicitis is inflammation of the appendix and is one of the most common surgical emergencies. When the blood supply to the appendix becomes compromised, the condition is termed gangrenous appendicitis. If the inflamed appendix ruptures, it is referred to as perforating appendicitis. When luminal obstruction is the precipitating factor, the condition is described as obstructive appendicitis.
Appendectomy remains the most frequent indication for abdominal surgery. In the United States, at least 250,000 cases of appendicitis occur annually, accounting for more than one million inpatient hospital days. Interestingly, the appendix is found to be normal in up to one-third of patients undergoing emergency appendectomy. Missed appendicitis is among the most common causes of successful malpractice claims against emergency department physicians. Males are affected slightly more often than females, with a male-to-female ratio of approximately 3:2. The lifetime risk is about 8.5% in men and 6.7% in women. Although appendicitis can occur at any age, peak incidence is in the second and third decades of life. Perforation is more common in infants and elderly patients.
The pathogenesis typically begins with luminal obstruction, most commonly caused by a fecalith. Other causes include foreign bodies, lymphoid hyperplasia (often associated with viral infections such as measles), parasitic worms, or tumors such as carcinoid or carcinoma. Obstruction leads to accumulation of mucus, bacterial overgrowth, and invasion of the appendiceal wall. Rising intraluminal pressure causes venous congestion, arterial compromise, ischemia, gangrene, and ultimately perforation. Ruptured appendiceal abscesses may form fistulas. Occasionally, appendicitis may be the first manifestation of Crohn’s disease, and in rare cases, recurrent acute appendicitis can occur with complete resolution between episodes.
Microbiologically, overgrowth of gastrointestinal flora occurs within the obstructed appendix. Common organisms include Escherichia coli, Bacteroides fragilis, Peptostreptococcus, Enterobacteriaceae, and viridans streptococci. Chronic infections due to tuberculosis, amebiasis, or actinomycosis are rare but documented causes.
Clinically, appendicitis classically begins with poorly localized, colicky periumbilical or epigastric pain due to visceral inflammation. As inflammation extends to the parietal peritoneum, pain becomes steady, more severe, and localized to the right lower quadrant at McBurney’s point. Movement and coughing aggravate the pain. Anorexia is common, and its absence should prompt reconsideration of the diagnosis. Nausea and vomiting occur in about half of patients, but vomiting rarely precedes pain. Urinary frequency or dysuria may occur if the inflamed appendix lies near the bladder.
Physical examination findings evolve with disease progression. Right lower quadrant tenderness eventually develops. Guarding, rebound tenderness, and percussion tenderness reflect peritoneal irritation. Rovsing’s sign refers to right lower quadrant pain elicited by palpation of the left lower quadrant. The psoas sign (pain with passive right hip extension) and obturator sign (pain with internal rotation of the flexed right hip) suggest retrocecal or pelvic appendiceal position. Fever is usually mild; temperatures above 38.3°C suggest perforation. A palpable right lower quadrant mass may indicate abscess formation or, less commonly, malignancy.
Laboratory evaluation commonly reveals leukocytosis between 10,000 and 18,000 cells/mm³ with a left shift, though normal white blood cell counts do not exclude appendicitis. Pregnancy testing is essential in women of childbearing age. Imaging plays a critical role in diagnosis. Computed tomography (CT) has an accuracy greater than 90% and improves resource utilization. Ultrasound is particularly useful in children and women of reproductive age to exclude gynecologic pathology. However, normal imaging should not override a convincing clinical picture.
The primary treatment is prompt surgical removal of the appendix. Preoperative antibiotics targeting gram-negative aerobes and anaerobes are standard. Regimens may include beta-lactam/beta-lactamase inhibitor combinations, ceftriaxone plus metronidazole, fluoroquinolone plus metronidazole, or carbapenems. Both laparoscopic and open appendectomy are acceptable approaches. Laparoscopic surgery is associated with less postoperative pain and fewer wound infections, though slightly higher rates of intra-abdominal abscess and increased cost.
In cases where a palpable mass develops several days after symptom onset, suggesting phlegmon formation, surgery may be delayed. These patients are managed with broad-spectrum antibiotics, intravenous fluids, and rest, with interval appendectomy performed approximately three months later unless clinical deterioration necessitates earlier intervention.
Prognosis is generally excellent, with mortality rates less than 1 per 100,000 in developed countries. However, perforated appendicitis carries a mortality rate of approximately 3%, rising to 15% in elderly patients. Delayed diagnosis increases the risk of perforation, which significantly raises postoperative complication rates, including intra-abdominal abscess, peritonitis, and wound infection. Rare complications include portal vein thrombophlebitis and pyogenic liver abscess. Early recognition and timely surgical management remain essential to prevent morbidity and mortality.
Appendicitis is inflammation of the appendix and is one of the most common surgical emergencies. When the blood supply to the appendix becomes compromised, the condition is termed gangrenous appendicitis. If the inflamed appendix ruptures, it is referred to as perforating appendicitis. When luminal obstruction is the precipitating factor, the condition is described as obstructive appendicitis.
Appendectomy remains the most frequent indication for abdominal surgery. In the United States, at least 250,000 cases of appendicitis occur annually, accounting for more than one million inpatient hospital days. Interestingly, the appendix is found to be normal in up to one-third of patients undergoing emergency appendectomy. Missed appendicitis is among the most common causes of successful malpractice claims against emergency department physicians. Males are affected slightly more often than females, with a male-to-female ratio of approximately 3:2. The lifetime risk is about 8.5% in men and 6.7% in women. Although appendicitis can occur at any age, peak incidence is in the second and third decades of life. Perforation is more common in infants and elderly patients.
The pathogenesis typically begins with luminal obstruction, most commonly caused by a fecalith. Other causes include foreign bodies, lymphoid hyperplasia (often associated with viral infections such as measles), parasitic worms, or tumors such as carcinoid or carcinoma. Obstruction leads to accumulation of mucus, bacterial overgrowth, and invasion of the appendiceal wall. Rising intraluminal pressure causes venous congestion, arterial compromise, ischemia, gangrene, and ultimately perforation. Ruptured appendiceal abscesses may form fistulas. Occasionally, appendicitis may be the first manifestation of Crohn’s disease, and in rare cases, recurrent acute appendicitis can occur with complete resolution between episodes.
Microbiologically, overgrowth of gastrointestinal flora occurs within the obstructed appendix. Common organisms include Escherichia coli, Bacteroides fragilis, Peptostreptococcus, Enterobacteriaceae, and viridans streptococci. Chronic infections due to tuberculosis, amebiasis, or actinomycosis are rare but documented causes.
Clinically, appendicitis classically begins with poorly localized, colicky periumbilical or epigastric pain due to visceral inflammation. As inflammation extends to the parietal peritoneum, pain becomes steady, more severe, and localized to the right lower quadrant at McBurney’s point. Movement and coughing aggravate the pain. Anorexia is common, and its absence should prompt reconsideration of the diagnosis. Nausea and vomiting occur in about half of patients, but vomiting rarely precedes pain. Urinary frequency or dysuria may occur if the inflamed appendix lies near the bladder.
Physical examination findings evolve with disease progression. Right lower quadrant tenderness eventually develops. Guarding, rebound tenderness, and percussion tenderness reflect peritoneal irritation. Rovsing’s sign refers to right lower quadrant pain elicited by palpation of the left lower quadrant. The psoas sign (pain with passive right hip extension) and obturator sign (pain with internal rotation of the flexed right hip) suggest retrocecal or pelvic appendiceal position. Fever is usually mild; temperatures above 38.3°C suggest perforation. A palpable right lower quadrant mass may indicate abscess formation or, less commonly, malignancy.
Laboratory evaluation commonly reveals leukocytosis between 10,000 and 18,000 cells/mm³ with a left shift, though normal white blood cell counts do not exclude appendicitis. Pregnancy testing is essential in women of childbearing age. Imaging plays a critical role in diagnosis. Computed tomography (CT) has an accuracy greater than 90% and improves resource utilization. Ultrasound is particularly useful in children and women of reproductive age to exclude gynecologic pathology. However, normal imaging should not override a convincing clinical picture.
The primary treatment is prompt surgical removal of the appendix. Preoperative antibiotics targeting gram-negative aerobes and anaerobes are standard. Regimens may include beta-lactam/beta-lactamase inhibitor combinations, ceftriaxone plus metronidazole, fluoroquinolone plus metronidazole, or carbapenems. Both laparoscopic and open appendectomy are acceptable approaches. Laparoscopic surgery is associated with less postoperative pain and fewer wound infections, though slightly higher rates of intra-abdominal abscess and increased cost.
In cases where a palpable mass develops several days after symptom onset, suggesting phlegmon formation, surgery may be delayed. These patients are managed with broad-spectrum antibiotics, intravenous fluids, and rest, with interval appendectomy performed approximately three months later unless clinical deterioration necessitates earlier intervention.
Prognosis is generally excellent, with mortality rates less than 1 per 100,000 in developed countries. However, perforated appendicitis carries a mortality rate of approximately 3%, rising to 15% in elderly patients. Delayed diagnosis increases the risk of perforation, which significantly raises postoperative complication rates, including intra-abdominal abscess, peritonitis, and wound infection. Rare complications include portal vein thrombophlebitis and pyogenic liver abscess. Early recognition and timely surgical management remain essential to prevent morbidity and mortality.
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Infectious Disease and Microbiology – Antibiotic and Clostridium difficile-Related Diarrhea
Antibiotic-associated diarrhea and colitis describe a spectrum of clinical syndromes that occur during or within 4–6 weeks after antibiotic therapy, resulting from disruption of normal intestinal flora. The diagnosis requires exclusion of other identifiable causes of diarrhea. Based on the degree of colonic involvement, disease ranges from normal colonic mucosa to mild erythema and edema, granular or hemorrhagic mucosa, and pseudomembrane formation. Clostridium difficile is the most common identifiable cause of antibiotic-associated colitis.
In the United States, C. difficile is responsible for approximately 3 million cases of diarrhea and colitis annually, with most cases occurring in hospitals or long-term care facilities, although community-acquired cases are increasingly recognized. Transmission occurs via spores spread from patient to patient, often through contaminated environmental surfaces and healthcare workers’ hands or equipment. While toxigenic C. difficile can be isolated from about 3% of healthy adults, colonization frequently develops during hospitalization, and roughly one-third of colonized individuals become symptomatic.
Major risk factors include antibiotic exposure, particularly clindamycin, ampicillin, amoxicillin, and cephalosporins, though virtually all broad-spectrum antibiotics can predispose to infection. Additional risk factors include hospitalization, advanced age, and severe underlying illness. Prevention strategies focus on strict enteric isolation precautions, use of gloves, private rooms when possible, and avoidance of unnecessary antibiotic use.
The pathogenesis begins with disruption of normal colonic flora, allowing C. difficile to proliferate. Most toxigenic strains produce two exotoxins, toxin A and toxin B. Toxin A is primarily responsible for enterotoxic effects, while toxin B is a potent cytotoxin. These toxins cause mucosal injury, inflammation, and in severe cases, pseudomembranous colitis.
Clinical presentation varies widely. Mild to moderate disease typically manifests with watery diarrhea and lower abdominal cramping without systemic symptoms. Moderate to severe colitis may present with profuse diarrhea, abdominal pain and distention, fever, nausea, anorexia, and malaise. Occult bleeding may occur. A subset of patients presents predominantly with right-sided colonic disease, marked leukocytosis, and abdominal pain but minimal diarrhea. Fulminant colitis may lead to ileus, toxic megacolon, or perforation. In contrast, non–C. difficile antibiotic-associated diarrhea is usually mild, dose-related, lacks systemic symptoms, and resolves rapidly after discontinuation of the offending antibiotic.
Physical examination may reveal abdominal tenderness ranging from mild to severe, and in advanced cases signs of peritonitis or systemic toxicity. Laboratory testing commonly includes enzyme immunoassay (EIA) for toxins A and B, complete blood count, and inflammatory markers. Leukocytosis with left shift is common, with white blood cell counts typically between 12,000 and 20,000/mm³, though leukemoid reactions can occur. Stool culture for C. difficile is rarely used because it does not differentiate toxigenic from non-toxigenic strains. Tissue culture cytotoxicity assay for toxin B is highly sensitive and specific but less commonly performed due to technical requirements and delayed results. Imaging with abdominal CT may demonstrate colonic wall thickening or edema. Endoscopy is reserved for selected cases, particularly when rapid diagnosis is needed or stool samples are unavailable.
Management begins with discontinuation of the inciting antibiotic whenever possible and supportive care with fluid and electrolyte replacement. Antiperistaltic agents should be avoided. Mild cases may resolve without specific therapy, but moderate or severe infections require targeted antimicrobial treatment. Oral metronidazole (500 mg three times daily) or oral vancomycin (125 mg four times daily) for 10–14 days are standard therapies. Metronidazole is often preferred initially due to lower cost and reduced risk of promoting vancomycin-resistant organisms, while vancomycin is preferred for severe disease, pregnancy, or in children under 10 years of age. Critically ill patients unable to take oral therapy may require rectal vancomycin administration or surgical intervention, such as subtotal colectomy.
Relapse occurs in 10–20% of patients, and recurrent episodes may require repeat therapy or tapered vancomycin regimens over several weeks. Fecal microbiota transplantation has been used successfully in severe or recurrent cases.
Complications include fulminant colitis, ileus, perforation, toxic megacolon, hyperpyrexia, reactive arthritis, chronic diarrhea, and hypoalbuminemia with anasarca. Monitoring should focus on clinical symptoms, as routine post-treatment testing is not recommended unless symptoms recur. Early recognition and prompt management are critical to reducing morbidity and mortality associated with severe disease.
Antibiotic-associated diarrhea and colitis describe a spectrum of clinical syndromes that occur during or within 4–6 weeks after antibiotic therapy, resulting from disruption of normal intestinal flora. The diagnosis requires exclusion of other identifiable causes of diarrhea. Based on the degree of colonic involvement, disease ranges from normal colonic mucosa to mild erythema and edema, granular or hemorrhagic mucosa, and pseudomembrane formation. Clostridium difficile is the most common identifiable cause of antibiotic-associated colitis.
In the United States, C. difficile is responsible for approximately 3 million cases of diarrhea and colitis annually, with most cases occurring in hospitals or long-term care facilities, although community-acquired cases are increasingly recognized. Transmission occurs via spores spread from patient to patient, often through contaminated environmental surfaces and healthcare workers’ hands or equipment. While toxigenic C. difficile can be isolated from about 3% of healthy adults, colonization frequently develops during hospitalization, and roughly one-third of colonized individuals become symptomatic.
Major risk factors include antibiotic exposure, particularly clindamycin, ampicillin, amoxicillin, and cephalosporins, though virtually all broad-spectrum antibiotics can predispose to infection. Additional risk factors include hospitalization, advanced age, and severe underlying illness. Prevention strategies focus on strict enteric isolation precautions, use of gloves, private rooms when possible, and avoidance of unnecessary antibiotic use.
The pathogenesis begins with disruption of normal colonic flora, allowing C. difficile to proliferate. Most toxigenic strains produce two exotoxins, toxin A and toxin B. Toxin A is primarily responsible for enterotoxic effects, while toxin B is a potent cytotoxin. These toxins cause mucosal injury, inflammation, and in severe cases, pseudomembranous colitis.
Clinical presentation varies widely. Mild to moderate disease typically manifests with watery diarrhea and lower abdominal cramping without systemic symptoms. Moderate to severe colitis may present with profuse diarrhea, abdominal pain and distention, fever, nausea, anorexia, and malaise. Occult bleeding may occur. A subset of patients presents predominantly with right-sided colonic disease, marked leukocytosis, and abdominal pain but minimal diarrhea. Fulminant colitis may lead to ileus, toxic megacolon, or perforation. In contrast, non–C. difficile antibiotic-associated diarrhea is usually mild, dose-related, lacks systemic symptoms, and resolves rapidly after discontinuation of the offending antibiotic.
Physical examination may reveal abdominal tenderness ranging from mild to severe, and in advanced cases signs of peritonitis or systemic toxicity. Laboratory testing commonly includes enzyme immunoassay (EIA) for toxins A and B, complete blood count, and inflammatory markers. Leukocytosis with left shift is common, with white blood cell counts typically between 12,000 and 20,000/mm³, though leukemoid reactions can occur. Stool culture for C. difficile is rarely used because it does not differentiate toxigenic from non-toxigenic strains. Tissue culture cytotoxicity assay for toxin B is highly sensitive and specific but less commonly performed due to technical requirements and delayed results. Imaging with abdominal CT may demonstrate colonic wall thickening or edema. Endoscopy is reserved for selected cases, particularly when rapid diagnosis is needed or stool samples are unavailable.
Management begins with discontinuation of the inciting antibiotic whenever possible and supportive care with fluid and electrolyte replacement. Antiperistaltic agents should be avoided. Mild cases may resolve without specific therapy, but moderate or severe infections require targeted antimicrobial treatment. Oral metronidazole (500 mg three times daily) or oral vancomycin (125 mg four times daily) for 10–14 days are standard therapies. Metronidazole is often preferred initially due to lower cost and reduced risk of promoting vancomycin-resistant organisms, while vancomycin is preferred for severe disease, pregnancy, or in children under 10 years of age. Critically ill patients unable to take oral therapy may require rectal vancomycin administration or surgical intervention, such as subtotal colectomy.
Relapse occurs in 10–20% of patients, and recurrent episodes may require repeat therapy or tapered vancomycin regimens over several weeks. Fecal microbiota transplantation has been used successfully in severe or recurrent cases.
Complications include fulminant colitis, ileus, perforation, toxic megacolon, hyperpyrexia, reactive arthritis, chronic diarrhea, and hypoalbuminemia with anasarca. Monitoring should focus on clinical symptoms, as routine post-treatment testing is not recommended unless symptoms recur. Early recognition and prompt management are critical to reducing morbidity and mortality associated with severe disease.
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Infectious Disease and Microbiology – Anthrax
Anthrax is a zoonotic infection primarily affecting herbivorous animals and only occasionally humans. The term derives from the Greek word for coal, referring to the characteristic black eschar seen in cutaneous disease. In humans, anthrax presents in three principal forms: cutaneous, inhalational (respiratory), and gastrointestinal. The incubation period ranges from 3–10 days for cutaneous disease and 3–5 days for pulmonary disease. Although rare in the United States, anthrax has been associated with exposure to contaminated wool, hides, and animal products, as well as foodborne outbreaks from tainted meat. The 2001 bioterrorism-related outbreak in the US resulted in 22 cases, including 11 inhalational cases and 5 deaths. A newer “injectional” form has been described among injection drug users, notably in Scotland, with significant mortality.
The causative agent, Bacillus anthracis, is an aerobic, gram-positive, spore-forming bacillus. Its spores are highly resistant to environmental stressors such as drying, radiation, and disinfectants and can persist in soil for years. Major risk factors in endemic developing regions include contact with contaminated soil or infected animals, while in urban areas exposure to contaminated animal products is more common. Prevention strategies include livestock vaccination, decontamination of animal products, and vaccination of high-risk groups such as military personnel, veterinarians, and individuals handling imported hides.
The pathogenesis of anthrax depends largely on the production of two binary toxins: lethal toxin and edema toxin. These toxins disrupt host immune responses and contribute to tissue necrosis, edema, and systemic toxicity. Clinically, cutaneous anthrax is the most common presentation. It begins as a painless papule that progresses to a vesicle and then to a characteristic black eschar measuring 1–3 cm, surrounded by edema. If untreated, cutaneous infection may progress to bacteremia and sepsis.
Inhalational anthrax often presents in two phases. The initial phase resembles a nonspecific viral upper respiratory illness lasting several days, followed by rapid deterioration with severe pneumonitis, respiratory distress, and systemic toxicity. Mediastinal widening on chest radiograph is a hallmark finding in advanced disease. The combination of mediastinal widening, altered mental status, and elevated hematocrit has been reported as highly sensitive in distinguishing inhalational anthrax from community-acquired pneumonia. Gastrointestinal anthrax presents with abdominal pain, nausea, vomiting, fever, and may include hematemesis or hematochezia. Injectional anthrax, seen in injection drug users, manifests with severe soft tissue infection, marked edema, and may include intracranial hemorrhage or gastrointestinal symptoms. Meningoencephalitis can complicate any form through hematogenous spread and may present with hemorrhagic cerebrospinal fluid and rapid progression to coma.
Diagnosis relies on clinical suspicion and laboratory confirmation. Gram stain and culture of vesicular fluid from cutaneous lesions typically demonstrate large, encapsulated gram-positive rods in short chains. Blood cultures are often positive in systemic disease, and stool cultures may reveal the organism in gastrointestinal infection. Chest imaging may show infiltrates, pleural effusions, and mediastinal widening. Differential diagnosis varies by presentation and includes tularemia, staphylococcal infections, spider bites, burns, bacterial or viral pneumonias, enteric bacterial infections, tuberculosis, and viral or amebic meningoencephalitis.
Treatment depends on disease severity and route of acquisition. Uncomplicated cutaneous anthrax in individuals older than two years can be treated with oral ciprofloxacin or doxycycline for 7–10 days. If susceptibility is confirmed, penicillin or amoxicillin may be used. Severe cutaneous disease requires intravenous therapy. Inhalational, gastrointestinal, or systemic anthrax requires prompt intravenous combination therapy, typically including ciprofloxacin plus one or two additional agents such as a carbapenem, rifampin, vancomycin, penicillin, chloramphenicol, or clindamycin. At least one agent with good central nervous system penetration should be included due to the risk of meningitis. In bioterrorism-related exposure, prolonged therapy for 60 days is recommended. Raxibacumab, a monoclonal antibody targeting anthrax toxin, has shown benefit in animal models of inhalational disease.
Prognosis depends on the form of disease and timeliness of treatment. Cutaneous anthrax generally responds well to therapy but often leaves a residual scar. Inhalational and gastrointestinal forms carry high mortality rates if not treated promptly. Close follow-up is required to monitor for recurrence or complications.
Anthrax is a zoonotic infection primarily affecting herbivorous animals and only occasionally humans. The term derives from the Greek word for coal, referring to the characteristic black eschar seen in cutaneous disease. In humans, anthrax presents in three principal forms: cutaneous, inhalational (respiratory), and gastrointestinal. The incubation period ranges from 3–10 days for cutaneous disease and 3–5 days for pulmonary disease. Although rare in the United States, anthrax has been associated with exposure to contaminated wool, hides, and animal products, as well as foodborne outbreaks from tainted meat. The 2001 bioterrorism-related outbreak in the US resulted in 22 cases, including 11 inhalational cases and 5 deaths. A newer “injectional” form has been described among injection drug users, notably in Scotland, with significant mortality.
The causative agent, Bacillus anthracis, is an aerobic, gram-positive, spore-forming bacillus. Its spores are highly resistant to environmental stressors such as drying, radiation, and disinfectants and can persist in soil for years. Major risk factors in endemic developing regions include contact with contaminated soil or infected animals, while in urban areas exposure to contaminated animal products is more common. Prevention strategies include livestock vaccination, decontamination of animal products, and vaccination of high-risk groups such as military personnel, veterinarians, and individuals handling imported hides.
The pathogenesis of anthrax depends largely on the production of two binary toxins: lethal toxin and edema toxin. These toxins disrupt host immune responses and contribute to tissue necrosis, edema, and systemic toxicity. Clinically, cutaneous anthrax is the most common presentation. It begins as a painless papule that progresses to a vesicle and then to a characteristic black eschar measuring 1–3 cm, surrounded by edema. If untreated, cutaneous infection may progress to bacteremia and sepsis.
Inhalational anthrax often presents in two phases. The initial phase resembles a nonspecific viral upper respiratory illness lasting several days, followed by rapid deterioration with severe pneumonitis, respiratory distress, and systemic toxicity. Mediastinal widening on chest radiograph is a hallmark finding in advanced disease. The combination of mediastinal widening, altered mental status, and elevated hematocrit has been reported as highly sensitive in distinguishing inhalational anthrax from community-acquired pneumonia. Gastrointestinal anthrax presents with abdominal pain, nausea, vomiting, fever, and may include hematemesis or hematochezia. Injectional anthrax, seen in injection drug users, manifests with severe soft tissue infection, marked edema, and may include intracranial hemorrhage or gastrointestinal symptoms. Meningoencephalitis can complicate any form through hematogenous spread and may present with hemorrhagic cerebrospinal fluid and rapid progression to coma.
Diagnosis relies on clinical suspicion and laboratory confirmation. Gram stain and culture of vesicular fluid from cutaneous lesions typically demonstrate large, encapsulated gram-positive rods in short chains. Blood cultures are often positive in systemic disease, and stool cultures may reveal the organism in gastrointestinal infection. Chest imaging may show infiltrates, pleural effusions, and mediastinal widening. Differential diagnosis varies by presentation and includes tularemia, staphylococcal infections, spider bites, burns, bacterial or viral pneumonias, enteric bacterial infections, tuberculosis, and viral or amebic meningoencephalitis.
Treatment depends on disease severity and route of acquisition. Uncomplicated cutaneous anthrax in individuals older than two years can be treated with oral ciprofloxacin or doxycycline for 7–10 days. If susceptibility is confirmed, penicillin or amoxicillin may be used. Severe cutaneous disease requires intravenous therapy. Inhalational, gastrointestinal, or systemic anthrax requires prompt intravenous combination therapy, typically including ciprofloxacin plus one or two additional agents such as a carbapenem, rifampin, vancomycin, penicillin, chloramphenicol, or clindamycin. At least one agent with good central nervous system penetration should be included due to the risk of meningitis. In bioterrorism-related exposure, prolonged therapy for 60 days is recommended. Raxibacumab, a monoclonal antibody targeting anthrax toxin, has shown benefit in animal models of inhalational disease.
Prognosis depends on the form of disease and timeliness of treatment. Cutaneous anthrax generally responds well to therapy but often leaves a residual scar. Inhalational and gastrointestinal forms carry high mortality rates if not treated promptly. Close follow-up is required to monitor for recurrence or complications.
