62 - SECTION 7 Miscellaneous Bacterial Infections

SECTION 7 Miscellaneous Bacterial Infections

TABLE 178-1  Effective Antibiotics for the Treatment of Donovanosis ANTIBIOTIC ORAL DOSE Azithromycin 1 g on day 1, then 500 mg daily for 7 days

or 1 g weekly for 4 weeks Trimethoprim-sulfamethoxazole 960 mg bid for 14 days Doxycycline 100 mg bid for 14 days Erythromycin 500 mg qid for 14 days (in pregnant women) Tetracycline 500 mg qid for 14 days condition is important, as are the administration of antibiotics and the monitoring of patients for an adequate interval (see below). Epidemiologic treatment of sexual partners and advice about how to improve genital hygiene are recommended. The recommended drug regimens for donovanosis are shown in Table 178-1. Gentamicin can be added if the response is slow. Ceftriaxone, chloramphenicol, and norfloxacin also are effective. Patients treated for 14 days should be monitored until lesions have healed completely. Those treated with azithromycin probably do not need such rigorous follow-up. Surgery may be indicated for very advanced lesions. ■ ■CONTROL AND PREVENTION Donovanosis is probably the cause of genital ulceration that is most readily recognizable clinically. Donovanosis is now limited to a few specific locations, and its global eradication is a distinct possibility. ■ ■FURTHER READING Muller EE, Kularatne R: The changing epidemiology of genital PART 5 Infectious Diseases ulcer disease in South Africa: Has donovanosis been eliminated? Sex Transm Infect 96:596, 2020. O’Farrell N: Donovanosis, in Sexually Transmitted Diseases, 4th ed. KK Holmes et al (eds). McGraw-Hill, 2008, pp 701–708. Rajam RV, Rangiah PN: Donovanosis (granuloma inguinale, granuloma venereum). Monogr Ser World Health Organ 24:1, 1954. Sehgal VN, Prasad AL: Donovanosis. Current concepts. Int J Dermatol 5:8, 1986. Section 7 Miscellaneous Bacterial Infections Michael S. Abers, Gregory A. Filice

Nocardiosis ■ ■INTRODUCTION Bacteria of the genus Nocardia are saprophytic filamentous aerobes ubiquitous in soil and water worldwide. In the past, the majority of isolates associated with pneumonia and systemic disease were iden­ tified biochemically as Nocardia asteroides, but the development of genome sequencing has demonstrated that at least 53 of the more than 100 species of Nocardia are associated with human disease. Most cases of systemic nocardiosis are caused by N. farcinica, N. cyriacigeorgica,

N. nova, N. abscessus, N. otitidiscaviarum, N. transvalensis, N. brasilien­ sis, N. pseudobrasiliensis, N. paucivorans, or N. brevicatena (Fig. 179-1). N. brasiliensis is usually associated with disease limited to the skin. Nocardiosis is usually an opportunistic infection, occurring primarily in individuals with impairments in host defenses. Infections follow­ ing local inoculation and pulmonary or systemic disease have distinct pathogenesis, microbiology, and management.

■ ■MICROBIOLOGY Nocardiae are Gram-positive, weakly acid-fast, and catalase positive. Like other members of the Mycobacteriales order, the cell walls of nocardiae contain mycolic acids (45–65 carbon atoms) and trehalose. Nocardia tend to clump together when grown in liquid media. On solid agar, Nocardia species typically form chalky, wrinkled colonies with a whitish-yellow or orange-brown hue. Growth is optimal at 37°C but can occur at temperatures up to 45°C. ■ ■EPIDEMIOLOGY AND RISK FACTORS Nocardiae are ubiquitous environmental saprophytes found in soil, water, and decaying organic matter worldwide. Humans are frequently exposed via inhalation or direct inoculation of the skin or an eye. Most immunocompetent individuals readily clear nocardiae without devel­ oping clinical disease. Certain impairments in host defenses predispose to invasive infection after inhalation. Primary cutaneous infection usually remains local. Nearly all cases are sporadic, but outbreaks have been reported in nosocomial settings among immunocompromised patients and in immunocompetent individuals related to surgical pro­ cedures or intravenous drug use. Person-to-person spread is not well documented. There is no known seasonality. The incidence of nocardiosis in the general population, estimated on three continents (North America, Europe, and Australia), is approxi­ mately ~0.375 cases per 100,000 persons per year. Nocardia infections are more common among adults than among children and more common among males than females. In contrast to the other forms of nocardiosis that occur worldwide, cases of actinomycetoma have been reported mostly in tropical and subtropical regions, especially in Mexico, Sudan, and India. The most important risk factors are lower socioeconomic status and frequent contact with soil or vegetable matter. Many cases are in laborers. Most cases of systemic nocardiosis occur in patients with host defense defects, including cell-mediated immunity and specific phago­ cyte defects. Those with nocardiosis typically possess one or more of the following risk factors: solid organ transplantation, hematopoietic stem cell transplantation, systemic corticosteroid use or Cushing syndrome, immunosuppressive therapy, or HIV infection. Among transplant recipients, risk factors for nocardiosis include corticoste­ roid dose, recent augmentation of immunosuppression for rejection or graft-versus-host disease, elevated calcineurin inhibitor levels, and patient age. Rare but well-described syndromes associated with nocar­ diosis include pulmonary alveolar proteinosis (PAP), neutralizing autoantibodies to granulocyte-macrophage colony-stimulating factor (GM-CSF), chronic granulomatous disease (CGD), and interleukin 12 (IL-12) or IL-12R deficiency. In the absence of any major risk factor for Nocardia infection, children and adults with nocardiosis should be tested for CGD. ■ ■PATHOGENESIS Pulmonary and systemic nocardiosis both occur following inhalation of fragmented bacterial mycelia. In healthy individuals, a variety of host defense mechanisms, including both innate and adaptive immune responses, help control and eliminate nocardiae from the respiratory tract without causing clinical disease. The importance of neutrophils and macrophages in antinocardial host defense is suggested by the fre­ quency of nocardiosis in patients with CGD. Nocardiae have evolved a number of properties that enable survival within phagocytes, including neutralization of oxidants, prevention of phagosome–lysosome fusion, and prevention of phagosome acidification. Neutrophils phagocytose nocardiae and limit their growth but do not kill them efficiently. Neutralizing autoantibodies against GM-CSF have been found in the majority of patients with autoimmune PAP and appear to be central to the pathogenesis of this disease. Nocardiae stimulate the production of GM-CSF in phagocytes in vitro, and extrapulmonary nocardiosis has been observed in several patients with autoantibodies to GM-CSF, most of whom had not had pulmonary alveolar proteinosis. The rela­ tionships between pulmonary alveolar proteinosis, nocardiosis, and antibodies to GM-CSF remain incompletely defined.