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J Hindler

Publications and source records attributed to J Hindler.

15 recordsLinked to original sources

Clinical applicability of antifungal susceptibility testing on non-Candida albicans species in hospitalized patients.

We assessed the distribution, antifungal susceptibility, and treatment associated with 161 non-Candida albicans isolates recovered from hospitalized patients over a 6-month period. The three most prevalent species were C. glabrata (100), C. tropicalis (28), and C. krusei (15). Resistance of C. glabrata to fluconazole and itraconazole were 6% and 17% respectively; 80% of the fluconazole-resistant isolates were cross-resistant to itraconazole. Prior azole exposure significantly reduced azole susceptibility in C. glabrata and also affected its subsequent selection among colonized patients. Only 21% of the patients had clinical infections. Patients with fungemia were more likely to be treated with amphotericin versus an azole. Overall treatment success was higher in patients treated with amphotericin versus an azole (56% vs 31%). Routine susceptibility testing on all Candida species does not appear necessary except where therapy with an azole is being considered to detect resistant isolates or for epidemiologic surveillance purposes. Further studies are needed to delineate the relationship between azole MICs and treatment outcomes of invasive candidiasis due to non-C. albicans species.

Amphotericin B↗

Quinupristin/Dalfopristin therapy for infections due to vancomycin-resistant Enterococcus faecium.

The efficacy and safety of quinupristin/dalfopristin for treatment of infections due to vancomycin-resistant Enterococcus faecium were evaluated in 24 hospitalized patients with documented infections (19 bacteremias, 5 localized infections) caused by vancomycin-resistant E. faecium that was susceptible to quinupristin/dalfopristin in vitro. Patients received iv quinupristin/dalfopristin at a dosage of either 7.5 mg/kg every 8 h or 5 mg/kg every 8 h. A favorable clinical response (cure or improvement) occurred in 19 (83%) of 23 evaluable patients; bacteriologic eradication occurred in 17 (74%) of 23 evaluable patients. A favorable clinical response was observed in 12 (80%) of 15 patients who were treated with 7.5 mg/kg of quinupristin/dalfopristin every 8 h and in 7 (88%) of 8 patients treated with 5 mg/kg of quinupristin/dalfopristin every 8 h. Two of four treatment failures were associated with a decrease in the in vitro susceptibility of vancomycin-resistant E. faecium to quinupristin/dalfopristin. Superinfections developed in 6 patients (26%), but only one was caused by Enterococcus faecalis that was resistant to quinupristin/dalfopristin. Myalgias and arthralgias were the only adverse events related to quinupristin/dalfopristin. These conditions occurred in 8 (33%) of 24 patients and were dose-related (8 cases in 16 patients treated with 7.5 mg/kg of quinupristin/dalfopristin every 8 h, no cases in 8 patients treated with 5 mg/kg every 8 h). Mortality associated with vancomycin-resistant E. faecium infection was 17% (4 of 23 patients), whereas mortality from other causes was 52% (12 of 23 patients). These results suggest that quinupristin/dalfopristin is effective as treatment for vancomycin-resistant E. faecium infections in critically ill patients with serious underlying conditions. Except for myalgias and arthralgias at higher dosages, the drug is well-tolerated.

Adolescent↗

SME-type carbapenem-hydrolyzing class A beta-lactamases from geographically diverse Serratia marcescens strains.

Three sets of carbapenem-resistant Serratia marcescens isolates have been identified in the United States: 1 isolate in Minnesota in 1985 (before approval of carbapenems for clinical use), 5 isolates in Los Angeles (University of California at Los Angeles [UCLA]) in 1992, and 19 isolates in Boston from 1994 to 1999. All isolates tested produced two beta-lactamases, an AmpC-type enzyme with pI values of 8.6 to 9.0 and one with a pI value of approximately 9.5. The enzyme with the higher pI in each strain hydrolyzed carbapenems and was not inhibited by EDTA, similar to the chromosomal class A SME-1 beta-lactamase isolated from the 1982 London strain S. marcescens S6. The genes encoding the carbapenem-hydrolyzing enzymes were cloned in Escherichia coli and sequenced. The enzyme from the Minnesota isolate had an amino acid sequence identical to that of SME-1. The isolates from Boston and UCLA produced SME-2, an enzyme with a single amino acid change relative to SME-1, a substitution from valine to glutamine at position 207. Purified SME enzymes from the U. S. isolates had beta-lactam hydrolysis profiles similar to that of the London SME-1 enzyme. Pulsed-field gel electrophoresis analysis revealed that the isolates showed some similarity but differed by at least three genetic events. In conclusion, a family of rare class A carbapenem-hydrolyzing beta-lactamases first described in London has now been identified in S. marcescens isolates across the United States.

Anti-Bacterial Agents↗

Comparative activity of twelve beta-lactam drugs tested against penicillin-resistant Streptococcus pneumoniae from five medical centers: effects of serum protein and capsular material on potency and spectrum as measured by reference tests.

A total of 152 strains of Streptococcus pneumoniae from diverse geographic areas in the United States and with different levels of penicillin resistance were tested against five broad-spectrum cephalosporins, ampicillin, piperacillin, ticarcillin, and three beta-lactamase inhibitor combinations. Also, the effect of human serum proteins on the activity of selected "third-generation" cephalosporins was examined. The overall rank order of activity among the cephalosporins against penicillin-susceptible strains was: ceftriaxone (MIC90, 0.03 microgram/mL) > cefotaxime > ceftizoxime = cefuroxime > ceftazidime (MIC90, 0.5 microgram/mL). Only cefotaxime and ceftriaxone exhibited significant activity against penicillin-intermediate or -resistant isolates. Ampicillin, piperacillin, and penicillin were generally eight- to 16-fold more potent than ticarcillin and no increase in the effectiveness of these agents was observed with the addition of the beta-lactamase inhibitors (clavulanate, sulbactam, tazobactam). Ceftriaxone potency was significantly decreased (> or = four-fold) by the modest addition of 25% pooled human serum proteins and this change modified the rank order of potency against nonpenicillin-susceptible pneumococci to favor cefotaxime (41% resistant versus 71% for ceftriaxone; MICs at > or = 2 micrograms/mL). Induced high-level capsular production had no measurable effect on the MIC results of tested agents. These results confirm the continued activity advantages of cefotaxime and ceftriaxone against various populations of pneumococci compared to other alternative beta-lactams. The predictive value, however, of the utilized breakpoint concentrations of the cephalosporins, remains in question for pneumococcal infections other than those in the central nervous system and at unaltered, "usual" dosing.

Anti-Bacterial Agents↗

Molecular characterization and multilaboratory evaluation of Enterococcus faecalis ATCC 51299 for quality control of screening tests for vancomycin and high-level aminoglycoside resistance in enterococci.

Studies were conducted to validate the use of Enterococcus faecalis ATCC 51299 (which is vancomycin resistant and resistant to high levels of gentamicin and streptomycin) and E. faecalis ATCC 29212 (which is susceptible to vancomycin and against which gentamicin or streptomycin and cell wall-active agents have synergistic kill activity) as controls in an agar screening test for vancomycin resistance and high-level streptomycin and gentamicin resistance and a broth microdilution screening test for high-level streptomycin and gentamicin resistance. Both organisms performed as expected in these tests and will serve as appropriate controls. However, E. faecalis ATCC 29212 was occasionally noted to produce light growth on the vancomycin screening plate with certain lots of agar. Quality control ranges for disk diffusion tests with disks with large amounts of streptomycin (300 micrograms) and gentamicin (120 micrograms) were established for E. faecalis ATCC 29212; zone limits are 16 to 22 mm for gentamicin and 14 to 19 mm for streptomycin. No zones for inhibition were seen when E. faecalis ATCC 51299 was tested with these high-content disks.

Aminoglycosides↗

Revised disk diffusion interpretive criteria for cefaclor, loracarbef, cefprozil and cefixime when testing Haemophilus influenzae on haemophilus test medium.

The aim of the current five-center collaborative study was to reassess the interpretive criteria for cefaclor, loracarbef, cefprozil and cefixime previously adopted or proposed by the National Committee for Clinical Laboratory Standards (NCCLS) for disk diffusion susceptibility tests with Haemophilus influenzae on Haemophilus Test Medium (HTM) agar. MICs and zones of inhibition were determined using NCCLS methods, HTM and two collections of strains of Haemophilus influenzae. One group of strains consisted of 118 stock organisms taken largely from various recent U.S. antibiotic resistance surveillance studies. The emphasis in this selected group of organisms was on strains that were beta-lactamase negative but ampicillin resistant (BLNAR) by some other mechanism. The second collection of test organisms consisted of 50 recent clinical isolates of Haemophilus influenzae obtained from each of the five participating study centers. This group was considered representative of the type of Haemophilus influenzae currently recovered from clinical sources in the USA. Frequency distribution assessment and error-rate bounded analysis of scattergram comparisons of MICs and zone sizes were used to develop the following zone diameters interpretive for disk diffusion susceptibility tests with Haemophilus influenzae on HTM agar: cefaclor, > or = 20 mm (susceptible, S) and < or = 16 mm (resistant, R); loracarbef, > or = 19 mm (S) and < or = 15 mm (R); and cefprozil, > 18 mm (S) and < 14 mm (R). The respective MIC correlates for all three antimicrobial agents were < or = 8 micrograms/ml (S) and 32 micrograms/ml (R).(ABSTRACT TRUNCATED AT 250 WORDS)

Cefaclor↗

Validation of NCCLS macrolide (azithromycin, clarithromycin, and erythromycin) interpretive criteria for Haemophilus influenzae tested with the Haemophilus test medium. National Committee for Clinical Laboratory Standards.

Some recently marketed macrolide antimicrobial agents possess physiochemical, antimicrobial, and pharmacokinetic advantages that enable their wider clinical use against Haemophilus influenzae infections. A five-laboratory study assessed the validity of existing or proposed azithromycin, clarithromycin, and erythromycin interpretive criteria for tests with H. influenzae isolates. National Committee for Clinical Laboratory Standards (NCCLS) methods, criteria, and quality-control guidelines were used. A total of 350 H. influenzae strains were processed, including fresh clinical isolates (250 strains) and replicate tests of 100 stock cultures sampling strains isolated from 1984 to 91. Azithromycin interpretive criteria (susceptible at < or = 4 micrograms/ml, > or = 12 mm) produced a 99.8% absolute agreement between the minimum inhibitory concentrations and disk diffusion results (0.2% false-susceptible error). Clarithromycin breakpoint criteria (susceptible at < or = 8 micrograms/ml, > or = 13 mm; and resistant at > or = 32 micrograms/ml, < or = 10 mm) produced high minor interpretive error, but < or = 1% combined false-susceptible and false-resistant discrepancies. Erythromycin interpretive guidelines were initially proposed for susceptible at < or = 0.5 microgram/ml, > or = 26 mm. This categorizes nearly all H. influenzae strains as resistant to this older macrolide. The NCCLS should consider the proposed erythromycin criteria for publication in appropriate tables, and a class drug should also be selected (azithromycin) that would best predict macrolide-class susceptibility for those agents indicated by the US Food and Drug Administration for H. influenzae infection chemotherapy (azithromycin and clarithromycin). No serious interpretive problems were observed with the current NCCLS criteria using Haemophilus test medium.

Anti-Bacterial Agents↗

Reliability of two novel methods, Alamar and E test, for detection of methicillin-resistant Staphylococcus aureus.

E test strips (AB Biodisk, Culver City, Calif.) tested on 2% NaCl-supplemented Mueller-Hinton agar and Alamar panels (Alamar, Sacramento, Calif.) correctly characterized 127 of 127 methicillin-resistant Staphylococcus aureus isolates and 100 of 100 methicillin-susceptible S. aureus isolates. These overnight antimicrobial susceptibility test systems reliably detect this clinically important resistance.

Drug Resistance, Microbial↗

Aminoglycoside resistance: a worldwide perspective.

Two concerns, neither of which is particularly new, underlie the current reluctance to use aminoglycosides more broadly. First, an undeniable fact is that these compounds can be toxic, particularly in patients with impaired renal function or those receiving other nephrotoxic medications. Second, a more emotional concern is that widespread use of aminoglycosides, particularly the newer compounds that are more resistant to enzymatic inactivation, may engender widespread resistance. In fact, several sources lead one to doubt whether widespread use of potent and highly effective agents like amikacin will by itself increase a clinical reservoir of more resistant microbes. First, the surveillance studies undertaken in many hospitals show some modest reduction in overall aminoglycoside resistance even when a drug like amikacin is used to supplant antecedent compounds of the same class. Second, in institutions where no official surveillance programs have been undertaken but where ongoing surveillance has been maintained, susceptibility to amikacin has remained constant when recent blood isolates are compared with blood isolates from more than 10 years ago. Third, in controlled clinical trials, particularly in immunocompromised patients, the overall emergence of resistance has been remarkably low and contrasts rather strikingly with what has been observed in some monotherapeutic studies of beta-lactam agents. The presence of aminoglycoside-resistant strains cannot be denied, but the circumstances leading to the emergence of such resistance must be carefully assessed, particularly outside of the setting in which these drugs are used as first-line therapy for critically ill patients. For instance, there is substantial evidence to suggest that the topical use of aminoglycosides or the use of these agents when there may be environmental contamination could lead to the emergence of resistance. Before one incriminates the use of any one drug as predisposing to the emergence of resistance, one needs to have more information about the total exposure of a given bacterial population to aminoglycoside therapy. The emergence of resistance to aminoglycosides has been associated with exposure to the more commonly used agents such as gentamicin or tobramycin. With some of the newer beta-lactam agents, the rate of emergence of resistance, unlike that of the aminoglycosides, has appeared to be remarkably high. If the concern about emergence of resistance is genuine, and to maintain consistency of approaches, the infectious disease community should focus more attention on limiting or restricting the use of the more widely used beta-lactam compounds.(ABSTRACT TRUNCATED AT 400 WORDS)

Amikacin↗

Strategies for antimicrobial susceptibility testing of fastidious aerobic bacteria.

There are several "non-standardized" test methodologies for performing antimicrobial susceptibility tests on clinical isolates of fastidious aerobic organisms. Critical to the interpretation of a susceptibility test (or any clinical laboratory test) is correlation of the results with the clinical status of the patient. If previous extensive studies have not been performed for a given antimicrobial-organism combination using a specific method, the results must be interpreted with discretion. Even when documented correlative data are available, strict quality control measures must be followed to ensure optimal performance of the test system. Ideally, these include testing of quality control organisms of known susceptibilities similar to the test isolate. Such quality control strains of fastidious organisms are not readily available; however, they may be obtained through local health departments. In our laboratory, in order to inform clinicians of the limitations of the results generated from antimicrobial susceptibility testing of fastidious aerobic bacteria using non-standardized (not NCCLS) procedures, we have adopted a mechanism for reporting results of disc tests as "presumptive" (Figure 1). When reporting dilution test results that are derived using methods other than those described by the NCCLS dilution protocol, we indicate the modifications employed in the particular test (Figure 2). Our goals are to attempt to identify unusual resistance that may occur and to generate results that are as accurate, precise, and meaningful as possible, yet we must be aware of the limitations of the procedures with which we are working (Table V). It is only with these understandings that we can be of service to our clinicians and patients.

Anti-Bacterial Agents↗

Use of trimethoprim-sulfamethoxazole singly and in combination with other antibiotics in immunocompromised patients.

Experience with trimethoprim-sulfamethoxazole (TMP-SMZ) alone or in combination with other agents in the treatment of immunocompromised patients other than those with Pneumocystis carinii pneumonitis and the acquired immunodeficiency syndrome is reviewed. A comparative study involving 126 episodes of fever showed a higher rate of response to a TMP-SMZ-carbenicillin regimen than to a gentamicin-carbenicillin combination (85% vs. 69%, respectively, P less than or equal to .04). In another study TMP-SMZ was used after unsuccessful therapy with the combination of an antipseudomonal penicillin and an aminoglycoside; 54% of the 35 patients treated orally and 49% of 86 treated intravenously responded to TMP-SMZ regimens. Other studies document successful results with TMP-SMZ used in combination with either an aminoglycoside or an antipseudomonal penicillin. TMP-SMZ has a role in the treatment of infections due to gram-negative bacilli in immunocompromised hosts, particularly when the infecting agent is not Pseudomonas aeruginosa and is resistant to moxalactam but susceptible to gentamicin.

Anti-Bacterial Agents↗