A randomized and blinded multicenter trial of high-dose fluconazole plus placebo versus fluconazole plus amphotericin B as therapy for candidemia and its consequences in nonneutropenic subjects.

A randomized, blinded, multicenter trial was conducted to compare fluconazole (800 mg per day) plus placebo with fluconazole plus amphotericin B (AmB) deoxycholate (0.7 mg/kg per day, with the placebo/AmB component given only for the first 5-6 days) as therapy for candidemia due to species other than Candida krusei in adults without neutropenia. A total of 219 patients met criteria for a modified intent-to-treat analysis.

Multiplex PCR for detection of aminoglycoside resistance genes in enterococci.

A multiplex PCR procedure for detecting the aminoglycoside resistance genes aac(6')-Ie-aph(2")-Ia, aph(2")-Ib, aph(2")-Ic, aph(2")-Id, aph(3')-IIIa, and ant(4')-Ia was evaluated and found to determine accurately the presence of these genes in enterococci.

Molecular characterization of gentamicin-resistant Enterococci in the United States: evidence of spread from animals to humans through food.

We evaluated the molecular mechanism for resistance of 360 enterococci for which the gentamicin MICs were >/=128 micro g/ml. The aac(6')-Ie-aph(2")-Ia, aph(2")-Ic, and aph(2")-Id genes were identified by PCR in isolates from animals, food, and humans. The aph(2")-Ib gene was not identified in any of the isolates.

A six-month trial of valacyclovir in the Epstein-Barr virus subset of chronic fatigue syndrome: improvement in left ventricular function.

This study was designed to determine safety and efficacy of a 6-month trial of valacyclovir in single-virus Epstein-Barr virus (EBV) persistent infection. Phase I of this study used four specific criteria to define a subset of patients with chronic fatigue syndrome (CFS). In the second phase, myocardial dynamics were measured by MUGA rest/stress radionuclide ventriculographic (RVG) examinations pre- and posttreatment with valacyclovir.

Fluconazole susceptibility of vaginal isolates obtained from women with complicated Candida vaginitis: clinical implications.

Despite considerable evidence of azole resistance in oral candidiasis due to Candida species, little is known about the azole susceptibilities of the genital tract isolates responsible for vaginitis. The fluconazole susceptibilities of vaginal isolates obtained during a multicenter study of 556 women with complicated Candida vaginitis were determined by evaluating two fluconazole treatment regimens. Of 393 baseline isolates of Candida albicans, 377 (96%) were highly susceptible to fluconazole (MICs, <8 microg/ml) and 14 (3.

Characterization of Tn1546 in vancomycin-resistant Enterococcus faecium isolated from canine urinary tract infections: evidence of gene exchange between human and animal enterococci.

Thirty-five enterococcal isolates were recovered from dogs diagnosed with urinary tract infections at the Michigan State University Veterinary Teaching Hospital over a 2-year period (1996 to 1998). Isolated species included Enterococcus faecium (n = 13), Enterococcus faecalis (n = 7), Enterococcus gallinarum (n = 11), and Enterococcus casseliflavus (n = 4). Antimicrobial susceptibility testing revealed several different resistance phenotypes, with the majority of the enterococcal isolates exhibiting resistance to three or more antibiotics.

The Role of Fluoroquinolones in the Treatment of Skin and Soft Tissue Infection.

Skin and soft tissue infections vary widely in their nature and severity, and their nomenclature is complex. Most are readily recognized and easily treated, but more severe infections may masquerade in forms similar to those of more innocent infections, causing delay in diagnosis and treatment that may result in loss of limb or life. Antimicrobial therapy is clearly beneficial for both recovery from these infections as well as preventing disease progression.

Association between the presence of enterococcal virulence factors gelatinase, hemolysin, and enterococcal surface protein and mortality among patients with bacteremia due to Enterococcus faecalis.

The potential virulence factors of enterococci include production of enterococcal surface protein (Esp), gelatinase, and hemolysin. Gelatinase- and hemolysin-producing strains of Enterococcus faecalis have been shown to be virulent in animal models of enterococcal infections. Esp production has been shown to enhance the persistence of E.

In vitro susceptibility of vancomycin-resistant enterococci (VRE) to fosfomycin.

We evaluated the in vitro activity of fosfomycin against 75 clinical isolates of vancomycin-resistant enterococci (VRE). Using the NCCLS breakpoint for susceptibility of urinary tract isolates to fosfomycin (MIC > or = 256), 51 out of 52 Enterococcus faecium and all Enterococcus faecalis isolates tested were susceptible or intermediate to fosfomycin.

Molecular analysis of vancomycin-resistant Enterococcus faecalis from Michigan hospitals during a 10 year period.

We evaluated the molecular relatedness of 47 clinical isolates of vancomycin-resistant Enterococcus faecalis collected from 15 Michigan hospitals from 1991 to 2000. There were 17 PFGE strain types for the 47 isolates. Ten of 15 hospitals demonstrated interhospital, and three of 15 intrahospital, dissemination of some isolates.

Thrombocytopenia associated with linezolid therapy.

We evaluated the incidence and clinical characteristics of linezolid-induced thrombocytopenia in 19 patients who were treated with linezolid. Overall, thrombocytopenia (platelet count, <100,000 platelets/mm(3)) was observed in 32% of patients who received linezolid for >10 days; gastrointestinal bleeding was observed in 1 patient and 4 patients required platelet transfusions. These data suggest that even patients who are not considered to be at risk for development of thrombocytopenia should be monitored closely if linezolid therapy is continued for >10 days.

Determinants of vancomycin resistance and mortality rates in enterococcal bacteremia. a prospective multicenter study.

Background: Enterococcus species are major nosocomial pathogens and are exhibiting vancomycin resistance with increasing frequency. Previous studies have not resolved whether vancomycin resistance is an independent risk factor for death in patients with invasive disease due to Enterococcus species or whether antibiotic therapy alters the outcome of enterococcal bacteremia.

Objective: To determine whether vancomycin resistance is an independent predictor of death in patients with enterococcal bacteremia and whether appropriate antimicrobial therapy influences outcome.

Heteroresistance to vancomycin in Enterococcus faecium.

This study presents the first report of vancomycin heteroresistance in an Enterococcus faecium isolate from a patient. The original isolate was susceptible in vitro to vancomycin. E-tests showed growth of subcolonies in a zone of inhibition with a vancomycin MIC of >256 microg/ml.

Treatment of complicated Candida vaginitis: comparison of single and sequential doses of fluconazole.

Objective: An attempt was made to validate recent recommendations that women with complicated Candida vaginitis (severe or recurrent, non-albicans Candida spp or abnormal host) require longer-duration antifungal therapy to achieve clinical cure and mycologic eradication.

Study Design: A prospective, multicenter, randomized, double-blind study was performed comparing a single dose of 150 mg of fluconazole with 2 sequential 150-mg doses of fluconazole given 3 days apart.

Results: Five hundred fifty-six women with severe or recurrent Candida vaginitis were enrolled, and 398 had at least one postbaseline evaluation (intent to treat) and of these 309 were fully evaluable (efficacy-valid).

Outbreak of sternal surgical site infections due to Pseudomonas aeruginosa traced to a scrub nurse with onychomycosis.

From 19 February 1999 through 31 October 1999, 16 (8.6%) of 185 patients who underwent median sternotomy developed infections with Pseudomonas aeruginosa. Seven patients had mediastinitis, 5 had deep sternal wound infection, 2 had superficial sternal wound infection, 1 had prosthetic valve endocarditis, and 1 had sepsis.

Clinical comparison of nonvented aerobic BacT/Alert blood culture bottle and standard aerobic bottle for detection of microorganisms in blood.

The current BacT/Alert standard aerobic (VA) blood culture bottle was redesigned and designated a nonvented aerobic (NVA) culture bottle; this bottle does not require venting. A total of 3,873 sets of blood samples for culture were obtained from adult patients with suspected bacteremia or fungemia. The NVA bottle showed performance equivalent to that of the VA bottle for recovery and speed of detection of microorganisms from blood without the need for venting the bottle.

Detection of the high-level aminoglycoside resistance gene aph(2")-Ib in Enterococcus faecium.

A new high-level gentamicin resistance gene, designated aph(2")-Ib, was cloned from Enterococcus faecium SF11770. The deduced amino acid sequence of the 897-bp open reading frame of aph(2")-Ib shares homology with the aminoglycoside-modifying enzymes AAC(6')-APH(2"), APH(2")-Ic, and APH(2")-Id. The observed phosphotransferase activity is designated APH(2")-Ib.

In-vitro synergistic activity of the combination of ampicillin and arbekacin against vancomycin-and high-level gentamicin-resistant Enterococcus faecium with the aph(2")-Id gene.

The combination of ampicillin plus arbekacin produced synergistic killing against 8 of 13 vancomycin-, ampicillin-, gentamicin-, and streptomycin-resistant Enterococcus faecium isolates that possess the high-level gentamicin resistance gene, aph(2")-Id. This combination may prove useful in treating infections caused by multiresistant enterococci.

Efficacy of ampicillin plus arbekacin in experimental rabbit endocarditis caused by an Enterococcus faecalis strain with high-level gentamicin resistance.

Enterococcus faecalis LC40 is an ampicillin-susceptible clinical isolate with high-level gentamicin resistance due to the aac(6')-Ie-aph(2")-Ia aminoglycoside resistance gene. The combination of ampicillin plus arbekacin reduced mean bacterial vegetation counts significantly more than ampicillin alone or ampicillin plus gentamicin in a rabbit model of aortic-valve endocarditis caused by E. faecalis LC40.

PCR fragment length polymorphism analysis of vancomycin-resistant Enterococcus faecium.

In this study, the glycopeptide resistance element, Tn1546, in 124 VanA Enterococcus faecium clinical isolates from 13 Michigan hospitals was evaluated using PCR fragment length polymorphism. There were 26 pulsed-field gel electrophoresis (PFGE) types, which consisted of epidemiologically related and unrelated isolates from separate patients (1992 to 1996). Previously published oligonucleotides specific for regions in the vanA gene cluster of Tn1546 were used to amplify vanRS, vanSH, vanHAX, vanXY, and vanYZ.

Comparison of a rabbit model of bacterial endocarditis and an in vitro infection model with simulated endocardial vegetations.

Animal models are commonly used to determine the efficacy of various antimicrobial agents for treatment of bacterial endocarditis. Previously we have utilized an in vitro infection model, which incorporates simulated endocardial vegetations (SEVs) to evaluate the pharmacodynamics of various antibiotics. In the present study, we compared four experimental rabbit endocarditis protocols to an in vitro infection model in an effort to determine if these models are comparable.

In-vitro activity of arbekacin alone and in combination with vancomycin against gentamicin- and methicillin-resistant Staphylococcus aureus.

In-vitro susceptibility studies were performed on 99 clinical Staphylococcus aureus isolates. A total of 68 of 73 methicillin-resistant S. aureus and 2 of 26 methicillin-susceptible S.

Candiduria: a randomized, double-blind study of treatment with fluconazole and placebo. The National Institute of Allergy and Infectious Diseases (NIAID) Mycoses Study Group.

Management of candiduria is limited by the lack of information about its natural history and lack of data from controlled studies on the efficacy of treating it with antimycotic agents. We compared fungal eradication rates among 316 consecutive candiduric (asymptomatic or minimally symptomatic) hospitalized patients treated with fluconazole (200 mg) or placebo daily for 14 days. In an intent-to-treat analysis, candiduria cleared by day 14 in 79 (50%) of 159 receiving fluconazole and 46 (29%) of 157 receiving placebo (P<.