Clinical characteristics and outcomes of diabetic patients with Staphylococcus aureus bacteremia and endocarditis.

The complications from S. aureus bacteremia (SAB) and infective endocarditis (SAIE) are higher in patients with diabetes. We summarize the characteristics and outcome of diabetic patients enrolled in a multicenter trial of daptomycin vs. standard therapy for SAB and SAIE. Adult patients with SAB were randomized to daptomycin 6 mg/kg/day or standard therapy (vancomycin 1 g every 12 h or antistaphylococcal penicillin 2 g every 4 h, both with gentamicin 1 mg/kg every 8 h for 4 days). Clinical success was defined as survival, resolution of S. aureus infection, and clinical outcome of cure or improved 6 weeks after end of therapy. Diabetic patients (86/235) were older, more overweight, and were more likely to present with systemic inflammatory response syndrome (SIRS) and to have complicated SAB. Clinical success rates were similar (67.4% in diabetics and 70.5% in non-diabetics). The mortality rate was significantly higher among diabetic patients (22.1% vs. 11.4%, p = 0.038). In the diabetes subgroup, the clinical success and mortality rates were comparable between the daptomycin and the standard therapy arms. The presence of diabetes is associated with significantly higher mortality in patients with SAB and SAIE. Daptomycin is an alternative therapeutic option in diabetic patients with these serious staphylococcal infections.

Outcomes with daptomycin versus standard therapy for osteoarticular infections associated with Staphylococcus aureus bacteraemia.

OBJECTIVES: To evaluate the clinical characteristics, treatment and outcomes of patients with osteoarticular infections (OAIs) associated with Staphylococcus aureus bacteraemia (SAB). METHODS: The clinical characteristics and outcomes for patients with OAI were described using a post hoc analysis of an open label, randomized trial comparing daptomycin with standard therapy (vancomycin or anti-staphylococcal penicillin with initial gentamicin) for the treatment of SAB. RESULTS: OAI occurred in 32 of 121 patients (21 daptomycin and 11 standard therapy) with complicated SAB (18 septic arthritis, 9 vertebral osteomyelitis and 7 others). Two patients had osteomyelitis in more than one site. Success rates seen in two groups were as follows: vertebral osteomyelitis [3/5 (60%) daptomycin versus 0/2 (0%) comparator], septic arthritis [7/11 (64%) versus 3/5 (60%)], sternal osteomyelitis [3/3 (100%) versus 1/2 (50%)] and long bone osteomyelitis [0/1 (0%) versus 1/1 (100%)]. Success rates in both treatment groups improved with surgical therapy. Creatine phosphokinase elevations to >500 IU/L occurred in one patient on daptomycin who discontinued therapy, whereas renal impairment developed in three patients on standard therapy, two of whom discontinued therapy. Two patients treated with daptomycin and one patient on vancomycin had increases in S. aureus MICs to daptomycin and vancomycin, respectively. Three patients treated with daptomycin died following completion of therapy, with mortality attributed to multiple co-morbid conditions and inadequate debridement of OAIs in these patients. No deaths were reported in the standard therapy group. CONCLUSIONS: Daptomycin may be considered an alternative to standard therapy in the treatment of patients with complicated SAB and OAI.

Chloramphenicol treatment for vancomycin-resistant Enterococcus faecium bacteremia.

OBJECTIVE: To evaluate the results of treating vancomycin-resistant Enterococcus faecium (VREF) bacteremia with chloramphenicol. METHODS: We retrospectively reviewed the charts of all adult patients with VREF bacteremia treated with chloramphenicol during the calendar year 1998 at a 522-bed tertiary referral center in New York City. Patients were identified by reviewing microbiology laboratory records. Patients with clinically significant VREF bacteremia who received chloramphenicol for at least 48 h were included in the study. Clinical and microbiological outcomes were determined. Microbiological and molecular tests were performed on a small representative sample of isolates to identify the presence of resistance mechanisms and to look for similarity among the isolates. RESULTS: Seven episodes of significant VREF bacteremia occurred in six patients. Mean age was 54 years. All patients had cancer and three had severe neutropenia. Five of seven episodes were associated with chronic indwelling devices, but in only one of these cases was the device removed. All isolates were susceptible to chloramphenicol in vitro. All six microbiologically evaluable episodes had a favorable response to chloramphenicol treatment, and four of seven (57%) clinically evaluable episodes had favorable outcomes. Only one death may have been due to VREF bacteremia, so the maximal attributable mortality was 14%. The three representative samples that were tested further were indistinguishable from one another and they displayed no evidence of resistance mechanisms. CONCLUSIONS: In a cohort of severely ill cancer patients, chloramphenicol was effective in treating VREF bacteremia. The use of chloramphenicol should be considered in treating infections with this highly resistant organism, where therapeutic options are limited.

In vivo activity of evernimicin (SCH 27899) against methicillin-resistant Staphylococcus aureus in experimental infective endocarditis.

Currently, there exist few satisfactory alternatives to vancomycin for therapy of serious methicillin-resistant Staphylococcus aureus (MRSA) infections. We employed a rat model of aortic valve endocarditis to assess the potential efficacy of evernimicin (SCH 27899) compared with vancomycin against infection with a strain susceptible to both agents (MICs of 0.25 and 0.50 microg/ml, respectively). Infected animals were assigned to one of three groups: controls (no treatment), evernimicin at 60 mg/kg of body weight by intravenous (i.v.) infusion once daily, or vancomycin at 150 mg/kg of body weight per day by continuous i.v. infusion. Therapy was administered for 5.5 days. At the start of therapy, colony counts in vegetations were 6.63 +/- 0.44 log(10) CFU/g. In both treatment groups, bacterial density within vegetations was significantly reduced in comparison with control animals that had not been treated. Final colony counts were as follows (mean +/- standard deviation): controls, 10.12 +/- 1.51 log(10) CFU/g of vegetation; evernimicin, 7.22 +/- 2.91 log(10) CFU/g of vegetation; vancomycin, 5.65 +/- 1.76 log(10) CFU/g of vegetation. The difference between the evernimicin and vancomycin groups was not significant. These results confirmed the bacteriostatic activity of evernimicin in vivo in an experimental model of severe MRSA infection.

In vitro activities of the glycylcycline GAR-936 against gram-positive bacteria.

The in vitro activities of GAR-936, the 9-t-butylglycylamido derivative of minocycline, were compared with those of doxycycline, minocycline, and tetracycline against 527 gram-positive clinical isolates. GAR-936 inhibited all strains, including those resistant to other tetracyclines, at concentrations of