Christine L. Terrell

General Principles of Antimicrobial Therapy

Antimicrobial agents are some of the most widely, and often injudiciously, used therapeutic drugs worldwide. Important considerations when prescribing antimicrobial therapy include obtaining an accurate diagnosis of infection; understanding the difference between empiric and definitive therapy; identifying opportunities to switch to narrow-spectrum, cost-effective oral agents for the shortest duration necessary; understanding drug characteristics that are peculiar to antimicrobial agents (such as pharmacodynamics and efficacy at the site of infection); accounting for host characteristics that influence antimicrobial activity; and in turn, recognizing the adverse effects of antimicrobial agents on the host. It is also important to understand the importance of antimicrobial stewardship, to know when to consult infectious disease specialists for guidance, and to be able to identify situations when antimicrobial therapy is not needed. By following these general principles, all practicing physicians should be able to use antimicrobial agents in a responsible manner that benefits both the individual patient and the community.

Pulmonary Cryptococcosis in Nonimmunocompromised Patients

BACKGROUND Cryptococcus neoformans can cause serious systemic infections requiring systemic antifungal therapy in immunocompromised hosts. However, isolated pulmonary cryptococcosis in nonimmunocompromised hosts has been reported to resolve spontaneously without treatment. STUDY OBJECTIVE s: To determine the role of antifungal therapy in the management of isolated pulmonary cryptococcosis in nonimmunocompromised hosts. DESIGN Retrospective study. SETTING Tertiary care, referral medical center PATIENTS Thirty-six nonimmunocompromised subjects with isolated pulmonary cryptococcosis who received diagnoses at the Mayo Clinic (Rochester, MN) from 1976 to 2001. INTERVENTIONS None. MEASUREMENTS AND RESULTS Of 42 nonimmunocompromised subjects with cryptococcal infections, 36 (86%) had isolated pulmonary cryptococcosis. The mean (+/- SD) age of these 36 patients was 61 +/- 15 years (range, 14 to 88 years), and the groups included 17 men (47%) and 19 women (53%). Twenty-four patients (67%) were symptomatic, and 12 patients (33%) were asymptomatic. The most common presenting symptoms were cough, dyspnea, and fever. Cultures of sputum and bronchial washings most commonly yielded the diagnosis. Cerebrospinal fluid examination was performed in 11 patients (31%) and was negative in all of them. Follow-up information was available on 25 patients (69%) with a median duration of 19 months (range, 1 to 330 months). Twenty-three of these patients (92%) had resolution of their disease (no treatment, 8 patients; surgical resection only, 6 patients; and antifungal therapy, 9 patients). The condition of the two remaining patients had improved. There was no documented treatment failure, relapse, dissemination, or death in any of these 25 patients. CONCLUSIONS Our findings suggest that an initial period of observation without the administration of antifungal therapy is a reasonable option for nonimmunocompromised subjects with pulmonary cryptococcosis in the absence of systemic symptoms or evidence of dissemination, as well as after surgical resection for focal cryptococcal pneumonia.

Antifungal Agents. Part II. The Azoles

Before 1978, amphotericin B and flucytosine were the only drugs available for the treatment of systemic fungal infections. The imidazoles, miconazole and ketoconazole, were introduced during the next 3 years. Intravenously administered miconazole served a limited therapeutic role and is no longer available. Orally administered ketoconazole, an inexpensive, effective, and convenient option for treating mucosal candidiasis, was widely used for a decade because it was the only available oral therapy for systemic fungal infections. During the 1990s, use of ketoconazole diminished because of the release of the triazoles--fluconazole and itraconazole. Fluconazole is less toxic and has several pharmacologic advantages over ketoconazole, including penetration into the cerebrospinal fluid. In addition, it has superior efficacy against systemic candidiasis, cryptococcosis, and coccidioidomycosis. Despite a myriad of drug interactions and less favorable pharmacologic and toxicity profiles in comparison with fluconazole, itraconazole has become a valuable addition to the antifungal armamentarium. It has excellent activity against sporotrichosis and seems promising in the treatment of aspergillosis. Itraconazole has replaced ketoconazole as the therapy of choice for nonmeningeal, non-life-threatening cases of histoplasmosis, blastomycosis, and paracoccidioidomycosis and is effective in patients with cryptococcosis and coccidioidomycosis, including those with meningitis. Further investigation into the development of new antifungal agents is ongoing.

The Aminoglycosides: Streptomycin, Kanamycin, Gentamicin, Tobramycin, Amikacin, Netilmicin, and Sisomicin

Despite the introduction of newer, less toxic antimicrobial agents, the aminoglycosides remain useful in the treatment of serious, hospital-acquired, gram-negative bacillary infections, especially those caused by Pseudomonas aeruginosa. Formidable nephrotoxicity and ototoxicity have limited the use of neomycin to topical or oral administration. Widespread antimicrobial resistance among Enterobacteriaceae has restricted the use of streptomycin and kanamycin to a few specific clinical situations. Gentamicin, tobramycin, and amikacin are active against a wide range of Enterobacteriaceae and many P. aeruginosa organisms. In medical centers where gentamicin resistance is prevalent, amikacin is the aminoglycoside of choice. Fortunately, amikacin resistance has not seemed to increase substantially, even in institutions where usage has been extensive for a long period. No new aminoglycoside has proved to be superior to amikacin.

Mycobacterium bovis Vertebral Osteomyelitis as a Complication of Intravesical BCG Use

We report a culture-proven case of Mycobacterium bovis vertebral osteomyelitis in a 76-year-old man who had undergone intravesical BCG therapy for bladder cancer 7 years previously. He presented with debilitating back pain and had radiographic evidence of T6-7 disk space destruction with involvement of adjacent vertebrae. Tissue culture from the disk space confirmed the diagnosis of vertebral osteomyelitis due to hematogenous spread of M. bovis. Treatment with antituberculous medications was begun soon after tissue diagnosis was made, and the patient fared well with medical therapy alone. Although uncommon, this infectious complication of BCG therapy should always be considered in the appropriate clinical setting. Timely diagnosis is important, because chemotherapy, when initiated early in the disease, can preclude the necessity for surgical intervention.

Mycobacterium fortuitum prosthetic valve endocarditis: a case for the pathogenetic role of biofilms

BACKGROUND Prosthetic valve endocarditis presents unique challenges for both diagnosis and treatment. A potential role of biofilm has been hypothesized in the pathogenesis of these infections. METHODS A patient with infective endocarditis involving a stentless (Freestyle) porcine prosthetic aortic valve with annular abscess and paravalvular leak 8 months after implantation is reported. RESULTS The infected valve did not show vegetations or perforations, but histiocytic inflammation was seen along the endocardial surfaces of the valve. Auramine-rhodamine staining revealed many acid-fast organisms associated with the inflammation. There was also an acellular matrix material with ultrastructural features of biofilm. Blood cultures grew Mycobacterium fortuitum, a biofilm-associated microbe. CONCLUSIONS The role of biofilm in prosthetic valve endocarditis is discussed. The importance of microscopy for prosthetic valves, even when no vegetations are present, is highlighted along with correlation of pathologic findings with culture results.

Laboratory-acquired Salmonella typhimurium enteritis:Association with erythema nodosum and reactive arthritis

A ccidental infection of workers in microbiology laboratories has long been recognized as an occupational hazard. Historically, diseases caused by microorganisms of high infectivity and pathogenicity, such as brucellosis, typhoid, tularemia, and tuberculosis, have predominated reports [1]. Laboratory-acquired infection with non-typhi Salmonella has rarely been reported. We report a case of laboratory-acquired Salmonella typhimurium infection associated with erythema nodosum, reactive arthritis, and episcleritis.