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Biomedical subjects

Irving Nachamkin

Publications and source records attributed to Irving Nachamkin.

At least 19 recordsLinked to original sources

Growth inhibition of Trichophyton species by Pseudomonas aeruginosa.

OBJECTIVE: To assess the ability of Pseudomonas aeruginosa to inhibit the growth of Trichophyton mentagrophytes (TM) and Trichophyton rubrum (TR). DESIGN: Pseudomonas aeruginosa, Escherichia coli, or Staphylococcus epidermidis were grown in co-culture with either TM or TR. SETTING: An academic medical center. MAIN OUTCOME MEASURES: The total fungal units and hyphal-spore ratio were measured at days 1, 5, 10, and 15. RESULTS: There was a 73% and 46% reduction of total fungal units and a final hyphal-spore ratio of 0.16 and 0.04, respectively, when TM and TR were co-cultured with P aeruginosa. The number of fungal units increased when TM and TR were cultured with E coli (28% and 42%, respectively), S epidermidis (13% and 18%, respectively), and control media (44% and 62%, respectively), and the hyphal-spore ratio increased to above 30 in the presence of S epidermidis, E coli, and control media. CONCLUSION: Pseudomonas aeruginosa exhibits growth inhibitory properties against TM and TR.

Coculture Techniques↗

Evaluation of mannitol salt agar, CHROMagar Staph aureus and CHROMagar MRSA for detection of meticillin-resistant Staphylococcus aureus from nasal swab specimens.

Mannitol salt agar (MSA), CHROMagar Staph aureus (CSA) and CHROMagar MRSA (CSA-MRSA) were evaluated with nasal surveillance specimens for their ability to detect Staphylococcus aureus and meticillin-resistant S. aureus (MRSA). CSA was found to be more sensitive than MSA in detecting S. aureus (98 versus 84.3 %; P=0.03). CSA and CSA-MRSA were equivalent in the ability to detect MRSA at 24 h (89.7 versus 87.2 %) and at 48 h (94.9 versus 94.9 %). When combined with Staphaurex slide confirmation testing, both CSA and CSA-MRSA were highly specific (100 %) media for detecting MRSA from nasal swab specimens.

Agar↗

Duration of outpatient fecal colonization due to Escherichia coli Isolates with decreased susceptibility to fluoroquinolones: longitudinal study of patients recently discharged from the hospital.

Among 10 subjects colonized with Escherichia coli isolates with reduced susceptibility to fluoroquinolones, the median duration of colonization following hospital discharge was 80 days (range, 8 to 172 days). Colonization was longer for isolates demonstrating organic-solvent tolerance than for isolates that were not organic-solvent tolerant (151 versus 29 days, respectively; P = 0.07) but was not associated with other resistance mechanisms, demographics, or antibiotic use.

Adult↗

Imipenem resistance among pseudomonas aeruginosa isolates: risk factors for infection and impact of resistance on clinical and economic outcomes.

OBJECTIVES: To identify risk factors for infection with imipenem-resistant Pseudomonas aeruginosa and determine the impact of imipenem resistance on clinical and economic outcomes among patients infected with P. aeruginosa. DESIGNS: An ecologic study, a case-control study, and a retrospective cohort study. SETTING: A 625-bed tertiary care medical center. PATIENTS: All patients who had an inpatient clinical culture positive for P. aeruginosa between January 1, 1999, and December 31, 2000. RESULTS: From 1991 through 2000, the annual prevalence of imipenem resistance among P. aeruginosa isolates increased significantly (P<.001 by the chi (2) test for trend). Among 879 patients infected with P. aeruginosa during 1999-2000, a total of 142 had imipenem-resistant P. aeruginosa infection (the case group), whereas 737 had imipenem-susceptible P. aeruginosa infection (the control group). The only independent risk factor for imipenem-resistant P. aeruginosa infection was prior fluoroquinolone use (adjusted odds ratio, 2.52 [95% confidence interval {CI}, 1.61-3.92]; P<.001). Compared with patients infected with imipenem-susceptible P. aeruginosa, patients infected with imipenem-resistant P. aeruginosa had longer subsequent hospitalization durations (15.5 days vs 9 days; P=.02) and greater hospital costs (81,330 dollars vs 48,381dollars ; P<.001). The mortality rate among patients infected with imipenem-resistant P. aeruginosa was 31.1%, compared with 16.7% for patients infected with imipenem-susceptible P. aeruginosa (relative risk, 1.86 [95% CI, 1.38-2.51]; P<.001). In multivariable analyses, there remained an independent association between infection with imipenem-resistant P. aeruginosa and mortality. CONCLUSIONS: The prevalence of imipenem resistance among P. aeruginosa strains has increased markedly in recent years and has had a significant impact on both clinical and economic outcomes. Our results suggest that curtailing use of other antibiotics (particularly fluoroquinolones) may be important in attempts to curb further emergence of imipenem resistance.

Adult↗

Reemergence of gram-negative health care-associated bloodstream infections.

BACKGROUND: Primary health care-associated bloodstream infections (PHA-BSIs) affect as many as 350 000 patients in the United States annually. Whereas gram-negative organisms were the leading cause before the 1970s, gram-positive organisms have been the predominant microbial isolates since then. METHODS: We identified all PHA-BSIs among adult inpatients in a 625-bed quaternary care hospital from January 1, 1996, through December 31, 2003, and evaluated trends in the microbial etiology, geographic distribution within the institution, and antimicrobial susceptibilities. RESULTS: A total of 3662 PHA-BSIs caused by 4349 bacterial and fungal isolates were identified. From 1999 to 2003, the proportion of PHA-BSIs due to gram-negative organisms increased from 15.9% to 24.1% (P<.001 for trend). This trend was not significantly different across various units of the hospital, and no specific gram-negative species contributed disproportionately to the increase. With few exceptions, there were no significant increases in antimicrobial resistance. The increase in gram-negative organisms was accompanied by a decline in the proportion of PHA-BSIs from coagulase-negative staphylococci (from 33.5% in 1999 to 29.9% in 2003, P = .007) and from Staphylococcus aureus (from 18.8% in 1999 to 11.8% in 2003, P = .004). The proportion of PHA-BSIs from Candida species almost doubled from 5.8% in 1999 to 11.3% in 2003 (P = .002). CONCLUSIONS: To our knowledge, this is the first US study to report a reemergence of gram-negative organisms as a cause of PHA-BSIs. This finding does not seem to be related to changes in specific gram-negative organisms or to antimicrobial resistance. If this trend continues, it will have important implications for the management of bloodstream infections.

Adult↗

Comparison of unit-specific and hospital-wide antibiograms: potential implications for selection of empirical antimicrobial therapy.

OBJECTIVE: To identify differences between unit-specific and hospital-wide antibiograms and to determine the potential impact of these differences on selection of empirical antimicrobial therapy. SETTING: A 625-bed tertiary care medical center. METHODS: Antimicrobial susceptibility results were collected for all inpatient clinical bacterial isolates recovered over a 3-year period; isolates were categorized by the hospital location of the patient at the time of sampling and by the anatomic site from which the isolate was recovered. Antibiograms from each unit were compiled for the most commonly isolated organisms and were compared to the hospital-wide antibiogram. RESULTS: A total of 9,970 bacterial isolates were evaluated in this study, including 2,646 enterococcal isolates, 2,806 S. aureus isolates, 2,795 E. coli isolates, and 1,723 Pseudomonas aeruginosa isolates. The percentages of bacterial isolates resistant to antimicrobials were significantly higher in the medical ICU and surgical ICU than the hospital-wide antibiogram would have predicted, whereas the percentages of isolates susceptible to antimicrobials were significantly higher in the non-ICU units, compared with the hospital overall. However, on general medicine units, the prevalence of susceptibility to levofloxacin was significantly lower than that for the hospital overall. CONCLUSIONS: Unit-specific antibiograms are important for making informed decisions about empirical antimicrobial therapy, because the hospital-wide antibiogram may mask important differences in susceptibility rates across different units. These differences may have important implications for selecting the optimal empirical antimicrobial therapy.

Anti-Infective Agents↗

Phenotypic and genotypic characterization of fecal Escherichia coli isolates with decreased susceptibility to fluoroquinolones: results from a large hospital-based surveillance initiative.

BACKGROUND: The prevalence of fecal colonization with Escherichia coli that has reduced susceptibility to fluoroquinolones is unknown. A detailed characterization of such isolates is limited. METHODS: We conducted 3 annual fecal surveillance initiatives at 2 hospitals from 2002 to 2004. All E. coli isolates with reduced susceptibility to fluoroquinolones (minimum inhibitory concentration [MIC] to levofloxacin, > or = 0.125 microg/mL) were identified. We characterized gyrA and parC mutations and organic solvent tolerance (OST). Isolates were compared using pulsed-field gel electrophoresis. RESULTS: Of 789 fecal samples, 149 (18.9%) revealed E. coli with reduced susceptibility to fluoroquinolones. Of 149 isolates, 102 (68.5%) had a MIC > or = 8 microg/mL, 138 (92.6%) had > or = 1 gyrA mutation, 101 (67.8%) had > or = 1 parC mutation, and 59 (39.6%) demonstrated OST. Isolates with a MIC > or = 8 versus <8 microg/mL had more target mutations (median, 3 vs. 1; P<.001) and more often exhibited OST (51% vs. 15%; P<.001). Of 149 isolates, 144 (96.6%) demonstrated a MIC > or = 16 microg/mL to nalidixic acid. The prevalence of OST differed across study years (P = .01). There was no clonal spread of isolates. CONCLUSIONS: Colonization by E. coli with reduced fluoroquinolone susceptibility is common, and fluoroquinolone-resistance characteristics differ significantly over time. Resistance to nalidixic acid may be useful in the identification of E. coli with early resistance mutations.

Anti-Bacterial Agents↗

Identification of optimal combinations for empirical dual antimicrobial therapy of Pseudomonas aeruginosa infection: potential role of a Combination Antibiogram.

To better determine the optimal combinations for empirical dual antimicrobial therapy of Pseudomonas aeruginosa infection, we evaluated the utility of a novel combination antibiogram. Although the combination antibiogram allowed modest fine-tuning of choices for dual antibiotic therapy, selections based on the 2 antibiograms did not differ substantively. Drug combinations with the broadest coverage were consistently composed of an aminoglycoside and a beta-lactam.

Anti-Bacterial Agents↗

Analysis and presentation of cumulative antimicrobial susceptibility data (antibiograms): substantial variability across medical centers in the United States.

We found substantial variability in approaches to constructing antibiograms at 65 United States medical centers. Laboratories in teaching hospitals and those with more personnel were significantly more likely to offer sophisticated antibiogram approaches, including the compiling of unit-specific susceptibility data and the reporting of temporal trends in susceptibility data.

Anti-Bacterial Agents↗

Limiting the emergence of extended-spectrum Beta-lactamase-producing enterobacteriaceae: influence of patient population characteristics on the response to antimicrobial formulary interventions.

BACKGROUND: Effective methods to control the emergence of extended-spectrum beta -lactamase-producing Escherichia coli and Klebsiella species (ESBL-EK) remain unclear. Variations in the patient populations at different hospitals may influence the effect of antimicrobial formulary interventions. METHODS: To examine variations across hospitals in the response to antimicrobial interventions (ie, restriction of ceftazidime and ceftriaxone) designed to curb the spread of ESBL-EK, we conducted a 5-year quasi-experimental study. This study was conducted at 2 hospitals within the same health system: Hospital A is a 625-bed academic medical center, and Hospital B is a 344-bed urban community hospital. All adult patients with a healthcare-acquired clinical culture of ESBL-EK from July 1, 1997 through December 31, 2002 were included. RESULTS: After the interventions, the use of ceftriaxone decreased by 86% at Hospital A and by 95% at Hospital B, whereas the use of ceftazidime decreased by 95% at Hospital A and by 97% at Hospital B. The prevalence of ESBL-EK at Hospital A decreased by 45% (P < .001), compared with a 22% decrease at Hospital B (P = .36). The following variables were significantly more common among ESBL-EK-infected patients at Hospital B: residence in a long-term care facility (adjusted odds ratio, 3.77 [95% confidence interval, 1.70-8.37]), advanced age (adjusted odds ratio, 1.04 [95% confidence interval, 1.01-1.06]), and presence of a decubitus ulcer (adjusted odds ratio, 4.13 [95% confidence interval, 1.97-8.65]). CONCLUSIONS: The effect of antimicrobial formulary interventions intended to curb emergence of ESBL-EK may differ substantially across institutions, perhaps as a result of differences in patient populations. Variability in the epidemiological profiles of ESBL-EK isolates at different hospitals must be considered when designing interventions to respond to these pathogens.

Adolescent↗

Fluoroquinolone-resistant Pseudomonas aeruginosa: assessment of risk factors and clinical impact.

PURPOSE: Pseudomonas aeruginosa infections have been associated with considerable morbidity and mortality. Fluoroquinolones (FQ) are the only oral therapy available for P. aeruginosa infections, but resistance is increasingly prevalent. METHODS: We examined annual trends in FQ-resistant P. aeruginosa (FQRPA) from 1991 to 2000. Subsequently, inpatients with a clinical culture positive for P. aeruginosa between January 1, 1999 and December 31, 2000 were included in a case control study to identify risk factors for FQ resistance and a cohort study to examine the impact of FQ resistance on outcomes in P. aeruginosa. RESULTS: Annual prevalence of FQRPA increased from 15% in 1991 to 41% in 2000 (P <0.001 trend). Between 1999 and 2000, 332 P. aeruginosa isolates were FQ resistant and 540 were FQ susceptible. Prior FQ use was the only independent risk factor for FQRPA (adjusted OR = 3.43; 95% confidence interval [CI] 2.37, 4.96). Subjects with FQRPA had greater median hospital charges (62,325 dollars vs 48,734 dollars) (P =.007) and higher mortality (47.5% vs 35.5%) (P =.004). However, in a multivariate model, only imipenem resistance of the isolate was significantly associated with mortality. FQ resistance was not an independent risk factor. CONCLUSIONS: FQRPA has increased significantly and is associated with prior FQ use. Limiting FQ use may curb the emergence of resistance among P. aeruginosa. FQRPA is associated with increased hospital charges, but other resistance patterns may have a more significant impact on mortality.

Academic Medical Centers↗

Use of BBL CHROMagar MRSA medium for identification of methicillin-resistant Staphylococcus aureus directly from blood cultures.

We evaluated the ability of BBL CHROMagar MRSA medium (Becton Dickinson, Sparks, MD) to identify methicillin-resistant Staphylococcus aureus (MRSA) directly upon subculture from positive blood culture bottles. There were 124 MRSA isolates recovered from blood cultures in the study. BBL CHROMagar MRSA medium was highly sensitive (97.6% [121/124] at 18 to 24 h of incubation and 100% [124/124] at 48 h) and 99.9% specific for identifying MRSA from positive blood cultures.

Anti-Bacterial Agents↗

Impact of inadequate initial antimicrobial therapy on mortality in infections due to extended-spectrum beta-lactamase-producing enterobacteriaceae: variability by site of infection.

BACKGROUND: Infections due to extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella species (ESBL-EK) have increased markedly in recent years. Risk factors for mortality among ESBL-EK infections have not been studied. METHODS: This retrospective cohort study was conducted in a 625-bed tertiary care medical center and a 344-bed urban community hospital to determine whether inadequate initial antimicrobial therapy (IIAT) (>48 hours between the time a culture was obtained and initiation of an agent to which the infecting organism was susceptible) is associated with mortality in ESBL-EK infections. All hospitalized patients with an ESBL-EK infection between June 1, 1997, and December 31, 2002, were eligible for inclusion. Subsequently, we conducted a nested case-control study to identify risk factors for IIAT. RESULTS: Of 187 subjects, 32 (17.1%) died while in the hospital. Clinical site of infection was a significant effect modifier in the association between IIAT and mortality. The presence of IIAT was an independent risk factor for mortality, but only for nonurinary ESBL-EK infections (adjusted odds ratio [95% confidence interval], 10.04 [1.90-52.96]). Independent risk factors for IIAT were (1) infection with a multidrug-resistant ESBL-EK (ie, resistant to sulfamethoxazole-trimethoprim, aminoglycosides, and quinolones) (14.58 [1.91-111.36]) and (2) health care-acquired ESBL-EK infection (4.32 [1.49-12.54]). CONCLUSIONS: Inadequate initial antimicrobial therapy is an independent risk factor for mortality in ESBL-EK infections, but only among nonurinary infections. Multidrug resistance was a strong risk factor for IIAT.

Aged↗

Risk factors for increasing multidrug resistance among extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella species.

BACKGROUND: The importance of infections due to extended-spectrum beta -lactamase-producing Escherichia coli and Klebsiella species (ESBL-EK) has been increasingly recognized in recent years. ESBL-EK infections are of clinical concern, because few antimicrobials are available as therapeutic options. Increased reliance on carbapenems has led to increasing carbapenem resistance. Efforts to maintain current therapeutic options for ESBL-EK infections are essential. METHODS: We conducted a case-control study to identify risk factors for multidrug resistance (MDR) among ESBL-EK. All patients at our institution who had an inpatient clinical culture result positive for an ESBL-EK during the period of 1 June 1997 through 31 December 2002 were eligible for inclusion. An MDR ESBL-EK was defined as ESBL-EK demonstrating resistance to trimethoprim-sulfamethoxazole, aminoglycosides, and quinolones. All available ESBL-EK isolates were characterized by pulsed-field gel electrophoresis (PFGE). RESULTS: Of 361 total ESBL-EK isolates, 68 (18.8%) were MDR. During the study period, the prevalence of MDR among ESBL-EK isolates increased from 12.5% to 26.9%. The only independent risk factor for MDR ESBL-EK was the infecting organism (i.e., Klebsiella pneumoniae; adjusted odds ratio, 11.7; 95% confidence interval, 4.77-28.51; P < .001). Prior antibiotic use was not independently associated with MDR ESBL-EK. PFGE patterns from K. pneumoniae isolates indicated close genetic relatedness among a substantial proportion of isolates. CONCLUSIONS: The emergence of MDR among ESBL-EK has important implications for the future ability to treat these infections. The strong association between the species of infecting organism and MDR suggests that the epidemiology in K. pneumoniae may be unique. PFGE results suggest that horizontal spread is important in the emergence of MDR ESBL-EK.

Adolescent↗

Test characteristics of perirectal and rectal swab compared to stool sample for detection of fluoroquinolone-resistant Escherichia coli in the gastrointestinal tract.

Among 63 patients enrolled in a prospective cohort study of gut colonization with fluoroquinolone-resistant Escherichia coli, the sensitivity of perirectal swab compared to stool sample was 90% (95% confidence interval [CI], 70 to 99%) and the specificity was 100% (95% CI, 91 to 100%). For rectal swab, the sensitivity was 90% (95% CI, 68 to 99%) and the specificity was 100% (95% CI, 91 to 100%).

Adult↗

Risk factors for and outcomes of bloodstream infection caused by extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella species in children.

OBJECTIVE: The increasing prevalence of infections caused by extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella species (ESBL-EK) has become a growing concern in the hospitalized patient population. Previous studies on risk factors for infection with ESBL-EK have mainly focused on adult populations, and these findings may not be relevant among the pediatric population that experiences a unique set of health care exposures and underlying conditions. The objective of this study was to define the risk factors and outcomes associated with ESBL-EK bloodstream infections in children. METHODS: We conducted a nested case-control study using data from the Children's Hospital of Philadelphia from May 1, 1999, to September 30, 2003. Eligible patients were identified from the hospital database of microbiology laboratory records. All patients with ESBL-EK bloodstream infections were compared to a random sample of patients with non-ESBL-EK bloodstream infections. Risk factors analyzed included prior antimicrobial use, comorbid conditions, and demographic characteristics. Pulsed-field gel electrophoresis was performed to determine genetic relatedness of the ESBL-EK isolates. RESULTS: Thirty-five cases and 105 control subjects were included in the study. The median age among the cases was 2 years (interquartile range: 0-11), compared with 1 year (interquartile range: 0-8) among control subjects. Patients with ESBL-EK infections were 5.8 times (95% confidence interval: 1.9-17.7) more likely to have had exposure to an extended-spectrum cephalosporin in the 30 days before infection than those with non-ESBL-EK infections. Other independent predictors of ESBL-EK infection were being female, infection with a Klebsiella species, and steroid use in the 30 days before infection. All ESBL-EK isolates were susceptible to carbapenem antibiotics. Pulsed-field gel electrophoresis analysis revealed that the ESBL-EK isolates were polyclonal. Although a substantially higher proportion of children with ESBL-EK died (in-hospital mortality: 36% vs 13%), this difference was not statistically significant. CONCLUSIONS: Receipt of extended-spectrum cephalosporins in the 30 days before infection by an Escherichia coli or Klebsiella species is significantly associated with having an ESBL-EK infection in hospitalized children. Curtailed use of cephalosporins among high-risk groups may reduce the occurrence of ESBL-EK infections. Future studies on identifying high-risk children and investigating the impact of curtailed third-generation cephalosporin use to limit additional emergence of ESBL-EK infections should be undertaken.

Analysis of Variance↗

Longitudinal trends in fluoroquinolone resistance among Enterobacteriaceae isolates from inpatients and outpatients, 1989-2000: differences in the emergence and epidemiology of resistance across organisms.

We conducted a 12-year study to identify and compare trends in annual prevalence of fluoroquinolone (FQ) resistance among Enterobacteriaceae isolates obtained from inpatients and outpatients in our health care system. A total of 46,070 clinical Enterobacteriaceae isolates underwent susceptibility testing. Although there were significant increases in inpatient FQ resistance for all Enterobacteriaceae, FQ resistance trends differed significantly across Enterobacteriaceae (P<.001). For isolates obtained from outpatients, only Escherichia coli and Proteus mirabilis demonstrated significant increases in FQ resistance (P<.001 for each). Trends in outpatient FQ resistance also differed significantly across Enterobacteriaceae (P<.001). There were significant differences between inpatient and outpatient FQ resistance trends for all Enterobacteriaceae except P. mirabilis and Enterobacter cloacae. Although hospital-wide use of certain antibiotics correlated significantly with inpatient FQ resistance, these correlations differed substantially across organisms. Efforts to elucidate the epidemiology of FQ resistance and identify targets for intervention must recognize and account for the variability of FQ resistance across organisms and clinical settings.

Anti-Infective Agents↗