Reduced vancomycin susceptibility and increased macrophage survival in Staphylococcus aureus strains sequentially isolated from a bacteraemic patient during a short course of antibiotic therapy.

PURPOSE: The purpose of the present study was to determine the relatedness of Staphylococcus aureus strains successively isolated over a 7-day period from a single bacteraemic patient undergoing antibiotic treatment with vancomycin. METHODS: The S. aureus strains had been isolated and sequenced previously. Antibiotic susceptibility testing, population analysis profiling, and lysostaphin sensitivity and phagocytic killing assays were used to characterize these clonal isolates. RESULTS: The seven isolates (MEH1-MEH7) were determined to belong to a common multilocus sequence type (MLST) and spa type. Within the third and fifth day of vancomycin treatment, mutations were observed in the vraS and rpsU genes, respectively. Population analysis profiles revealed that the initial isolate (MEH1) was vancomycin-susceptible S. aureus (VSSA), while those isolated on day 7 were mostly heteroresistant vancomycin-intermediate S. aureus (hVISA). Supporting these findings, MEH7 was also observed to be slower in growth, to have an increase in cell wall width and to have reduced sensitivity to lysostaphin, all characteristics of VISA and hVISA strains. In addition, MEH7, although phagocytosed at numbers comparable to the initial isolate, MEH1, survived in higher numbers in RAW 264.7 macrophages. Macrophages infected with MEH7 also released more TNF-α and IFN-1ß. CONCLUSION: We report an increasing resistance to vancomycin coupled with daptomycin that occurred within approximately 3 days of receiving vancomycin and steadily increased until the infection was cleared with an alternative antibiotic therapy. This study reiterates the need for rapid, efficient and accurate detection of hVISA and VISA infections, especially in high-bacterial load, metastatic infections like bacteraemia.

Draft Genome Sequences of Two Staphylococcus aureus Strains Isolated in Succession from a Case of Bacteremia.

Staphylococcus aureus strains MEH1 and MEH7 were successively isolated from the blood of a patient with recurrent bacteremia. The submitted draft genomes of strains MEH1 and MEH7 are 2,914,972 and 2,911,704 bp, respectively.

Cryptococcosis in human immunodeficiency virus-negative patients in the era of effective azole therapy.

We conducted a case study of human immunodeficiency virus (HIV)-negative patients with cryptococcosis at 15 United States medical centers from 1990 through 1996 to understand the demographics, therapeutic approach, and factors associated with poor prognosis in this population. Of 306 patients with cryptococcosis, there were 109 with pulmonary involvement, 157 with central nervous system (CNS) involvement, and 40 with involvement at other sites. Seventy-nine percent had a significant underlying condition. Patients with pulmonary disease were usually treated initially with fluconazole (63%); patients with CNS disease generally received amphotericin B (92%). Fluconazole was administered to approximately two-thirds of patients with CNS disease for consolidation therapy. Therapy was successful for 74% of patients. Significant predictors of mortality in multivariate analysis included age > or =60 years, hematologic malignancy, and organ failure. Overall mortality was 30%, and mortality attributable to cryptococcosis was 12%. Cryptococcosis continues to be an important infection in HIV-negative patients and is associated with substantial overall and cause-specific mortality.

Cat-scratch disease presenting as neuroretinitis and peripheral facial palsy.

A 40-year-old woman with Cat-scratch disease sought treatment for neuroretinitis OD and right peripheral facial nerve palsy. To our knowledge, this is the first case of an adult with a peripheral facial nerve palsy from Cat-scratch disease and the first case of a patient with both neuroretinitis and peripheral facial nerve palsy.

Grapefruit juice decreases the systemic availability of itraconazole capsules in healthy volunteers.

The systemic availability of itraconazole capsules may be reduced secondary to elevated gastric pH and possibly by presystemic intestinal metabolism via CYP3A4. Grapefruit juice is acidic and an inhibitor of intestinal CYP3A4. To determine the effect of grapefruit juice on the systemic availability of itraconazole capsules, serum itraconazole and hydroxy-itraconazole concentrations were determined in eleven healthy volunteers studied in a randomized, two-way crossover design. Concurrent grapefruit juice resulted in a 43% decrease in the mean itraconazole AUC0-48 (2507 ng x hr/mL versus 1434 ng x hr/mL, p = 0.046) and a 47% decrease in the mean hydroxy-itraconazole AUC0-72 (7264 ng x hr/mL versus 3880 ng x hr/mL, p = 0.025). Grapefruit juice also significantly increased the mean itraconazole Tmax (5.5 versus 4 hours). We conclude that concomitant grapefruit juice does not enhance the systemic availability of itraconazole capsules, but rather appears to impair itraconazole absorption. Therefore, concomitant grapefruit juice will not likely be useful in improving the oral availability of itraconazole capsules.

Vertebral blastomycosis with paravertebral abscess: report of eight cases and review of the literature.

Bone is the third most frequent site of disease in patients with blastomycosis, and the vertebrae are among the bones affected most often. We describe the clinical features and treatment of eight patients with vertebral blastomycosis and review the literature regarding this disease. All eight patients had destructive vertebral lesions evident on radiographs, and all had clinical or radiographic evidence of a contiguous abscess. The lower thoracic or lumbar regions were affected most often. Fever and skin lesions typical of blastomycosis were variably present. All but one patient had an abnormal chest radiograph. Treatment included long-term antifungal therapy and drainage of large fluid collections. Five of the eight patients were cured of their disease. Of the other 3 patients, 1 is still receiving therapy and is probably cured, 1 died of blastomycosis, and the status of 1 is unknown. In areas of endemicity, blastomycosis should be a diagnostic consideration for any patient with a destructive vertebral lesion.

Clinical approach to infective endocarditis.

The epidemiology of IE has evolved over the past 50 years. Mitral valve prolapse and degenerative valvular disease have replaced rheumatic heart disease as the most common predisposing conditions. The average age of patients with IE has increased, and nosocomially acquired cases are becoming more common. Although viridans streptococci are currently responsible for a smaller proportion of cases than previously, this group of bacteria remains the most common cause of prosthetic value and native valve endocarditis. Staphylococci are the most important cause in some community hospitals, in nosocomial IE, and in IVDUs. IE is a multisystem disease, and patients may present with diverse clinical features. In the absence of direct histopathologic and microbiologic examination of valvular vegetations, the diagnosis of IE depends on the detection of endocardial abnormalities and the isolation of a pathogen from blood. Blood culture remains the most important laboratory test and yields the causative microorganism in 95% of patients. Echocardiography has become an important tool for detecting endocardial lesions. The clinical features of IE in IVDUs are somewhat different than those in other populations. The microbiology is distinctive, and right-sided involvement with septic pulmonary emboli is the most common clinical scenario in this group.