Although late cases occur, the first year after SOT is the period of highest risk for histoplasmosis. In patients who survive the first month after diagnosis, treatment with an amphotericin formulation followed by an azole for 12 months is usually successful, with only rare relapse.
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In this study, disease outcomes were generally favorable. Discontinuation of antifungal treatment after clinical response and an appropriate duration of therapy, probably at least 12 months, appears safe if pharmacologic immunosuppression has been held. Resumption of TNF-α blocker therapy also appears safe, assuming that the initial antifungal therapy was administered for 12 months.
ᰔRecent studies have questioned treatment of serious methicillinresistant Staphylococcus aureus (MRSA) infections with vancomycin because of treatment failures, despite vancomycin MICs in the susceptible category (MIC Յ 2 g/ml) (2, 3, 5, 6, 7). Some of these studies have used broth microdilution for determining vancomycin MICs (5), while others have used the Etest commercial product (AB Biodisk, Solna, Sweden) (2, 7). We sought to determine if substantive differences might result from using different susceptibility test methods for determining vancomycin MICs.A group of 101 previously characterized strains of MRSA recovered between 2002 and 2006 from bacteremic patients in our institution were selected. Fifteen to 25 isolates per year were chosen, with MICs in the range of 0.5 to 2 g/ml, based upon initial tests. Isolates were stored frozen at Ϫ70°C in skim milk and subcultured twice prior to being tested. Each isolate was tested by the CLSI broth microdilution and the CLSI agar dilution methods (1) and by the Etest method using two different brands of Mueller-Hinton agar plates (BBL agar [BD Microbiology Systems, Cockeysville, MD] and Remel agar [Remel, Lenexa, KS]). All tests were performed at the same time from the same inoculum suspension.Results are depicted in Table 1. Vancomycin MICs generated by Etest were consistently one twofold dilution higher than MICs determined by CLSI broth or agar dilution; i.e., the modal vancomycin MIC determined by both the CLSI broth and agar dilution methods was 1 g/ml, while the modal vancomycin MIC by Etest was 2 g/ml with both Mueller-Hinton agar brands. In fact, 89 to 98% of MICs were 1.5 or 2 g/ml by Etest, but only 3 to 12% of vancomycin MICs were 2 g/ml when determined by the CLSI broth or agar dilution method.Our findings raise several issues. Pharmacodynamic studies have shown that the area under the vancomycin concentration curve-to-MIC ratio (AUC/MIC) is the optimal method for predicting vancomycin efficacy against S. aureus infections (7). Furthermore, the probability of achieving an optimal AUC/MIC ratio has been shown to be much lower when the vancomycin MIC is 2 g/ml than when it is 1 g/ml (4). Therefore, even a one dilution difference in the MIC can substantially affect the MIC/AUC ratio and the ability to optimize treatment (7). If differences of only one dilution are relevant to predicting clinical outcomes of MRSA infections, the MIC method used is a critical part of the equation.The differences between MICs generated by the Etest and
Effective therapeutic options are needed for community-onset urinary tract infections due to Escherichia coli strains that produce CTX-M extended-spectrum -lactamases. We examined 46 urinary isolates producing CTX-M against several oral or long-acting parenteral antimicrobial agents. Approximately 90% were susceptible to fosfomycin and to a combination of cefdinir plus amoxicillin-clavulanate. All were susceptible to ertapenem.Since the early 1990s, Escherichia coli isolates that produce CTX-M extended-spectrum -lactamases (ESBLs) have emerged as a serious cause of urinary tract infections (UTIs) in the community (18). Mortality in the more severe infections, particularly those progressing to bacteremia, is as high as 60.8% (14). Chances of survival increase with appropriate initial antibiotic coverage, while delay in proper therapy is associated with increased mortality (14). Empirical antibiotic therapy, particularly in the outpatient setting, is problematic as most of these organisms are resistant to fluoroquinolones, trimethoprim-sulfamethoxazole, oral cephalosporins, and amoxicillin-clavulanate (18,22). The primary goal of this investigation was to identify potential treatment options for outpatient UTIs with these organisms. We tested several candidate oral antibiotics and one long-acting parenteral agent against a collection of genetically characterized ESBL-producing isolates.The ESBLs produced by each isolate were characterized by PCR amplification followed by sequencing of PCR products as previously described (13). A total of 45 UTI isolates (predominantly E. coli) that produced a CTX-M alone (40 producing CTX-M15, three producing CTX-M16, and one each producing CTX-M8 and CTX-M14) and one isolate that produced a CTX-M15 and an SHV-2 ESBL were examined along with 11 isolates that produced only SHV (four producing SHV-12, three producing SHV-2, and three producing SHV-5) or TEM-10 ESBLs. All isolates were recovered between 2002 and 2008. Isolates were stored frozen at Ϫ70°C in skim milk and subcultured twice prior to susceptibility testing. Each isolate was tested for susceptibility to fosfomycin by the CLSI agar dilution method (4) and to ciprofloxacin, doxycycline, ertapenem, and nitrofurantoin and to a novel combination of cefdinir plus a fixed concentration of amoxicillin-clavulanate by the CLSI broth microdilution method (4). For testing the unique combination of cefdinir and amoxicillin-clavulanate, the cefdinir was diluted in the usual twofold dilution scheme in a fixed concentration of 8 g/ml amoxicillin and 4 g/ml clavulanate. Both cefdinir and amoxicillin-clavulanate were tested separately in the normal twofold dilution format to ascertain their activities when tested alone. The calculation of the percentage of isolates susceptible to the three-drug combination was based upon the cefdinir component and use of the approved cefdinir-susceptible breakpoint of Յ1 g/ml (5).Results are summarized in Table 1. Approximately 90% of urinary CTX-M ESBL-producing isolates were susceptible to the combina...
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