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Aim: To examine the prevalence of antimicrobial-resistant Salmonella in chicken meat and correlate with isolates from ill humans., Methods: We isolated Salmonella from raw chicken purchased from a randomly selected sample of retail outlets in central Pennsylvania during 2006-2007. Salmonella isolates from meat were compared, using pulsed-field gel electrophoresis, to isolates in the PulseNet database of Salmonella recovered from humans., Results: Of 378 chicken meat samples, 84 (22%) contained Salmonella. Twenty-six (31%) of the Salmonella isolates were resistant to > or = 3 antimicrobials and 18 (21%) were resistant to ceftiofur. All ceftiofur-resistant isolates exhibited reduced susceptibility (minimum inhibitory concentration >2 microg/mL) to ceftriaxone and carried a bla(CMY) gene, as detected by polymerase chain reaction. Among the 28 Salmonella serovar Typhimurium isolates, 20 (71.4%) were resistant to > or = 3 antimicrobials and 12 (42.9%) were resistant to ceftiofur. One ceftiofur-resistant Salmonella serovar Typhimurium poultry isolate exhibited a rare pulsed-field gel electrophoresis pattern indistinguishable from a human isolate in PulseNet; both isolates carried the bla(CMY-2) gene., Conclusions: These data demonstrate the presence of multidrug-resistant Salmonella in poultry meat, including bla(CMY) plasmid-mediated genes that confer resistance to both ceftiofur, used in poultry, and ceftriaxone, used for treating salmonellosis in humans. This study illustrates the potential for molecular subtyping databases to identify related Salmonella isolates from meat and ill humans, and suggests that chicken could be a source for multidrug-resistant salmonellosis in humans.

Background: Fluoroquinolones are the most commonly prescribed antimicrobials. The epidemiology of fecal colonization with Escherichia coli demonstrating reduced susceptibility to fluoroquinolones remains unclear., Methods: During a 3-year period (15 September 2004 through 19 October 2007), all patients hospitalized for >3 days were approached for fecal sampling. All E. coli isolates with reduced susceptibility to fluoroquinolones (minimum inhibitory concentration [MIC] of levofloxacin, 0.125 microg/mL) were identified. We characterized gyrA and parC mutations and organic solvent tolerance. Isolates were compared using pulsed-field gel electrophoresis., Results: Of 353 patients colonized with E. coli demonstrating reduced fluoroquinolone susceptibility, 300 (85.0%) had 1 gyrA mutation, 161 (45.6%) had 1 parC mutation, and 171 (48.6%) demonstrated organic solvent tolerance. The mean numbers of total mutations (ie, gyrA and parC) for E. coli isolates with a levofloxacin MIC of 8 microg/mL versus <8.0 microg/mL were 2.70 and 0.82 (P < .001). Of the 136 E. coli isolates with a levofloxacin MIC of 8 microg/mL, 90 (66.2%) demonstrated a nalidixic acid MIC of 16 microg/mL. Significant differences were found over time in the proportion of E. coli isolates demonstrating gyrA mutation, parC mutation, and organic solvent tolerance. There was little evidence of clonal spread of isolates. Conclusions. Gastrointestinal tract colonization with E. coli demonstrating reduced susceptibility to levofloxacin is common. Although 40% of study isolates exhibited a levofloxacin MIC of <8 microg/mL (and would thus be missed by current Clinical and Laboratory Standards Institute breakpoints), nalidixic acid resistance may be a useful marker for detection of such isolates. Significant temporal changes occurred in the proportion of isolates exhibiting various resistance mechanisms.

Background: Although Candida glabrata is an emerging infection, risk factors for fluconazole resistance in patients with C glabrata bloodstram infection (BSI) have not been well elucidated., Methods: A case-control study was conducted to evaluate the primary risk factor of interest, previous fluconazole use, adjusting for demographics, comorbidities, time at risk, and antimicrobial exposure and assessing for effect modification. Secondary analyses were performed limiting the case group to C glabrata BSIs with a minimum inhibitory concentration (MIC) > or =64 microg/mL., Results: Previous fluconazole use was not a significant risk factor for fluconazole-resistant C glabrata BSI in primary analysis (adjusted odds ratio [aOR], 1.5; 95% confidence interval [CI], 0.7-3.2) but was borderline significant in secondary analysis (aOR, 3.2; 95% CI, 0.9-11.3). Increased time at risk was an independent risk factor in primary (aOR, 1.02; 95% CI, 1.002-1.04) and secondary analyses (aOR, 1.03; 95% CI, 1.004-1.06)., Conclusion: Increased time at risk was the only significant risk factor for fluconazole resistance. Future studies are needed to further evaluate the relationship between previous fluconazole use and fluconazole-resistant C glabrata BSI isolates with MIC > or =64 microg/mL., (Copyright 2010 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.)

Background: There are limited data comparing the clinical presentations, comorbidities, and outcomes of patients with infections due to seasonal influenza with patients with infections due to pandemic (H1N1) 2009 influenza., Objective: To compare the epidemiological characteristics and outcomes of pandemic (H1N1) 2009 influenza with those of seasonal influenza., Methods: A cross-sectional study was conducted among patients who received diagnoses during emergency department and inpatient encounters at 2 affiliated academic medical centers in Philadelphia, Pennsylvania. Cases of seasonal influenza during the period November 1, 2005, through June 1, 2008, and cases of pandemic influenza during the period from May 1, 2009, through August 7, 2009, were identified retrospectively., Results: Forty-nine cases of pandemic influenza and 503 cases of seasonal influenza were identified. Patients with pandemic H1N1 were younger (median age, 29 years) than patients with seasonal influenza (median age, 59 years) (P<.001). More patients with pandemic H1N1 (35 [71%] of 49) were African American, compared with patients with seasonal influenza (267 [53%] of 503; P=.02). Several symptoms were more common among patients with pandemic influenza infections than among patients with seasonal influenza infections: cough (98% vs 83%; P=.007), myalgias (71% vs 46%; P=.001), and pleuritic chest pain (45% vs 15%; P<.001). Pregnancy was the only comorbidity that occurred significantly more often in the pandemic influenza group than in the seasonal influenza group (16% vs 1%; P<.001). There were no significant differences in frequencies of deaths of hospitalized patients, intensive care unit admission, or length of hospitalization between groups., Conclusion: Other than pregnancy, there were few clinically important differences between infections due to seasonal influenza and those due to pandemic influenza. The greater rate of lower respiratory tract symptoms in pandemic cases might serve to differentiate pandemic influenza from seasonal influenza.

Among pediatric and adult providers, 70% preferred trimethoprim-sulfamethoxazole for directed treatment of community-associated methicillin-resistant Staphylococcus aureus skin and soft-tissue infections, although a higher proportion of pediatric compared with adult providers favored clindamycin (36% vs 8%, respectively, P < .0001). For recurrent infections, 88% of providers employed at least 1 topical decolonization strategy., (Copyright (c) 2010 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.)

Objective: To compare the incidence of liver toxicity and clinical response between 2 initial dosing regimens of methotrexate (MTX) for treatment of juvenile idiopathic arthritis (JIA)., Methods: Clinical and laboratory data were abstracted from the medical records of 220 children newly prescribed MTX from the same geographic region. One cohort received initial doses of MTX > 0.5 mg/kg/week ("high-dose") and one cohort received initial doses of MTX

We studied exclusion policies and child care center directors' opinions regarding antibiotic use for childhood illnesses. Among 135 respondents, 96.9% reported that they had written policies on exclusion of children for acute illnesses. Although 52.4% of respondents agreed that children are prescribed antibiotics unnecessarily, 89.1% believed that parents pressure physicians to prescribe unnecessary antibiotics.

Background: The emergence of H1N1 influenza is cause for great concern. Although one of the most important components of the response to the H1N1 crisis is the work of health care epidemiology professionals, the beliefs and experiences of this community are unknown, and the optimal approach to managing H1N1 in the future has not been delineated., Methods: To assess attitudes and responses of health care epidemiology professionals to the H1N1 influenza crisis, we conducted a cross-sectional survey of members of the Society for Healthcare Epidemiology of America. We assessed beliefs regarding (1) importance of H1N1, (2) institutional preparedness, (3) time spent on the H1N1 crisis, and (4) the institution's response to H1N1., Results: Of 323 respondents, 195 (60.4%) reported that their hospitals were well prepared for a pandemic. Furthermore, the majority reported that senior administrators provided adequate political support and resources (85.1% and 80.2%, respectively) to respond to H1N1. However, 163 (50.9%) respondents reported that other important infection prevention activities were neglected during the H1N1 crisis. Shortages of antiviral medication were reported by 99 (30.7%) respondents. Furthermore, 126 (39.0%) reported that personal stockpiling of antiviral medications occurred at their institution, and 166 (51.4%) reported that institutional actions were initiated to prevent personal stockpiling. Also, 294 (91.0%) respondents believed that H1N1 influenza would reappear later this year. Vaccine development, health care worker education, and revisions of pandemic influenza plans were identified as the most important future initiatives. Finally, 251 (77.7%) respondents felt that health care workers should be mandated to receive influenza vaccine., Conclusions: Although generally institutions are well prepared for the H1N1 crisis, substantial revisions of pandemic preparedness plans appear to be necessary. Future efforts to optimize the response to H1N1 should include curtailing personal stockpiling of antivirals and vaccine development with consideration of mandatory vaccination of health care workers.

Background: Pseudomonas aeruginosa is one of the most common gram-negative hospital-acquired pathogens. Resistance of this organism to imipenem complicates treatment., Objective: To elucidate the risk factors for imipenem-resistant P. aeruginosa (IRPA) infection or colonization and to identify the effect of resistance on clinical and economic outcomes., Methods: Longitudinal trends in prevalence of IRPA from 2 centers were characterized during the period from 1989 through 2006. For P. aeruginosa isolates obtained during the period from 2001 through 2006, a case-control study was conducted to investigate the association between prior carbapenem use and IRPA infection or colonization, and a cohort study was performed to identify the effect of IRPA infection or colonization on mortality, length of stay after culture, and hospital cost after culture., Results: From 1989 through 2006, the proportion of P. aeruginosa isolates demonstrating resistance to imipenem increased from 13% to 20% (P < .001, trend). During the period from 2001 through 2006, there were 2,542 unique patients with P. aeruginosa isolates, and 253 (10.0%) had IRPA isolates. Prior carbapenem use was independently associated with IRPA infection or colonization (adjusted odds ratio [OR], 7.92 [95% confidence interval {CI}, 4.78-13.11]). Patients with an IRPA isolate recovered had higher in-hospital mortality than did patients with an imipenem-susceptible P. aeruginosa isolate (17.4% vs 13.4%; P = .01). IRPA infection or colonization was an independent risk factor for mortality among patients with isolates recovered from blood (adjusted OR, 5.43 [95% CI, 1.72-17.10]; P = .004) but not among patients with isolates recovered from other anatomic sites (adjusted OR, 0.78 [95% CI, 0.51-1.21]; P = .27). Isolation of IRPA was associated with longer hospital stay after culture (p < .001) and greater hospital cost after culture (P < .001) than was isolation of an imipenem-susceptible strain. In multivariable analysis, IRPA infection or colonization remained an independent risk factor for both longer hospital stay after culture (coefficient, 0.20 [95% CI, 0.04-0.36]; P = .02) and greater hospital cost after culture (coefficient, 0.30 [95% CI, 0.06-0.54]; P = .02)., Conclusions: The prevalence of IRPA infection or colonization has increased significantly, with important implications for both clinical and economic outcomes. Interventions to curb this continued increase and strategies to optimize therapy are urgently needed.

Background: Acinetobacter baumannii is an emerging gram-negative pathogen that can cause healthcare-acquired infections among patients. Treatment is complicated for cases of healthcare-acquired infection with A. baumannii resistant to imipenem., Objective: To elucidate the risk factors for imipenem-resistant A. baumannii (IRAB) infection or colonization and to identify the effect of resistance on clinical and economic outcomes., Methods: We analyzed data from 2 medical centers of the University of Pennsylvania. Longitudinal trends in the prevalence of IRAB clinical isolates were characterized during the period from 1989 through 2004. For A. baumannii isolates obtained from 2001 through 2006, a case-control study was conducted to investigate the association between prior carbapenem use and IRAB infection or colonization, and a cohort study was performed to identify the effect of IRAB infection or colonization on mortality, length of stay after culture, and hospital cost after culture., Results: From 1989 through 2004, the annual prevalence of IRAB isolates ranged from 0% to 21%. During the period from 2001 through 2006, there were 386 unique patients with A. baumannii isolates, and 89 (23.1%) had IRAB isolates. Prior carbapenem use was independently associated with IRAB infection or colonization (adjusted odds ratio, 3.04 [95% confidence interval, 1.07-8.65]). There was a borderline significant association between IRAB infection or colonization and mortality, although this association was limited to isolates recovered from blood samples (adjusted odds ratio, 5.30 [95% confidence interval, 0.81-34.59]). Compared with patients with imipenem-susceptible A. baumannii infection or colonization, patients with IRAB infection or colonization had a longer hospital stay after culture (median, 21 vs 16 days; P = .07) and greater hospital charges after culture (mean, $334,516 vs $276,059; P = .03). After controlling for patient location in an intensive care unit, transfer from another facility, and length of hospital stay before culture, there was no longer an independent association between IRAB infection or colonization and higher cost after culture and length of stay after positive culture result., Conclusions: Many A. baumannii isolates exhibit imipenem resistance, which is strongly associated with prior use of carbapenems. Given the high mortality rate associated with A. baumannii infection or colonization, interventions to curb further emergence of cases of IRAB infection and strategies to optimize therapy are needed.

Background: Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae is an emerging pathogen with serious clinical and infection control implications. To our knowledge, no study has specifically examined risk factors for KPC-producing K. pneumoniae or its impact on mortality., Methods: To identify risk factors for infection or colonization with KPC-producing K. pneumoniae, a case-control study was performed. Case patients with KPC-producing K. pneumoniae were compared with control subjects with carbapenem-susceptible K. pneumoniae. A cohort study evaluated the association between KPC-producing K. pneumoniae and in-hospital mortality., Results: Fifty-six case patients and 863 control subjects were identified. In multivariable analysis, independent risk factors for KPC-producing K. pneumoniae were (1) severe illness (adjusted odds ratio [AOR], 4.31; 95% confidence interval [CI], 2.25-8.25), (2) prior fluoroquinolone use (AOR, 3.39; 95% CI, 1.50, 7.66), and (3) prior extended-spectrum cephalosporin use (AOR, 2.55; 95% CI, 1.18, 5.52). Compared with samples from other anatomic locations, K. pneumoniae isolates from blood samples were less likely to harbor KPC (AOR, 0.33; 95% CI, 0.12, 0.86). KPC-producing K. pneumoniae was independently associated with in-hospital mortality (AOR, 3.60; 95% CI, 1.87-6.91)., Conclusions: KPC-producing K. pneumoniae is an emerging pathogen associated with significant mortality. Our findings highlight the urgent need to develop strategies for prevention and infection control. Limiting use of certain antimicrobials, specifically fluoroquinolones and cephalosporins, use may be effective strategies.

We identified 1,805 gram-negative organisms in cultures of urine samples obtained over a 10-month period from residents of 63 long-term care facilities. The prevalence of fluoroquinolone resistance in Escherichia coli was 51% (446 of 874 isolates), whereas the prevalences of ceftazidime and imipenem resistance in Klebsiella species were 26% and 6% (84 and 19 of 323 isolates), respectively. The prevalence of resistance varied significantly by facility type, size, and geographic location.

About two years ago, the death of a high school student athlete brought methicillin-resistant Staphylococcus aureus (MRSA) into the national spotlight. Preventing the spread of MRSA in schools, gyms, and other public facilities is an important public health goal. This Issue Brief presents current information on the prevalence and transmission of MRSA in community settings, and describes ongoing research on interventions to limit the spread of this increasingly common infection.

This report describes Pennsylvania's 9-year experience in implementing training programs to strengthen public health response to emerging infectious diseases. During the biannual 3-5-day-long Pennsylvania Public Health Institute (PHI) events, which have been held since 2000, courses have covered topics such as emerging infectious disease outbreaks, monitoring of antimicrobial-resistant pathogens in retail food, and zoonotic diseases commonly associated with companion animals. Core competency courses include the legal basis for public health and epidemiology for nonepidemiologists. Emerging infectious disease seminars offered to clinicians since 2005 have focused on the emergence of community-associated methicillin-resistant Staphylococcus aureus and Clostridium difficile antibiotic-associated diarrhea. Complementing the PHI, the Pennsylvania Department of Health's monthly Epidemiology Journal Club offers additional interactions with presenters from academic institutions and federal agencies. Lunch-time forums also provide a venue for health department staff to share their work with colleagues. Innovative use of modern communication technology increases participation of frontline health workers in Journal Club events, and video conference capability offers flexibility in the selection of presenters. Pennsylvania's experience over the past 9 years demonstrates that with political will, commitment from content experts, and adequate administrative support, modest state and federal resources can be used to sustain public health training programs tailored to local needs.

Of 57 case-control studies of antimicrobial resistance, matching was used in 23 (40%). Matched variables differed substantially across studies. Of these 23 matched case-control studies, 12 (52%) justified the use of matching, and 9 (39%) noted the strengths or limitations of this approach. Analysis that accounted for matching was performed in only 52% of the case-control studies.

Of 49 long-term care facility residents, 21 (43%) were colonized with 2 or more distinct strains of Escherichia coli. There were no significant risk factors for colonization with multiple strains of E. coli. These results suggest that future efforts to efficiently identify the diversity of colonizing strains will be challenging.

Objective: During fall 2005, personal stockpiling of oseltamivir for use during an outbreak of H5N1 influenza virus infection was widely reported. The present study aimed to identify indications for oseltamivir prescriptions to determine whether oseltamivir that was not intended for seasonal influenza was inappropriately consumed and to compare persons who were likely to have stockpiled oseltamivir and those who did not with respect to their knowledge, understanding, concerns, and expectations regarding avian influenza., Design: Survey to evaluate usage patterns for oseltamivir and assess views about avian influenza., Subjects: A total of 109 outpatients who received a prescription for oseltamivir between September 1, 2005, and December 31, 2005, and 825 matched control subjects., Results: Of 109 prescriptions, 36 (33.0%) were prescribed for patients with appropriate indications. Sixty-eight (62.4%) of 109 patients identified as having received oseltamivir and 440 (53.3%) of 825 individuals identified as not having received it responded to the questionnaire. Only 2 prescription recipients whose oseltamivir was not intended for immediate consumption reported that they had consumed the oseltamivir. Persons who probably intended to stockpile oseltamivir were older and more often white than those unlikely to stockpile it. They also reported greater worry about avian influenza and more often expected avian influenza to spread to the United States than those unlikely to stockpile, but there were no significant differences in responses to other questionnaire items., Conclusions: A large proportion of the oseltamivir prescriptions written in fall 2005 were probably intended for personal stockpiling. Similarities in participants' responses to questionnaire items suggest that educational campaigns may not be an effective method to curtail stockpiling of antimicrobial medications during an infectious threat. Promoting appropriate prescribing practices among providers may be a better means by which to minimize personal stockpiling.

We studied provider- and patient-collected samples from multiple anatomic sites to determine the yield for detection of methicillin-resistant Staphylococcus aureus (MRSA). Sampling of multiple sites was required to achieve a sensitivity of more than 90% for MRSA colonization. Groin and perineum samples yielded positive results significantly more often for community-onset MRSA than for hospital-onset MRSA. Agreement rates between provider- and patient-collected swab specimens were excellent.

Objective: Staphylococcus aureus infections after cardiac surgery result in significant morbidity and mortality. Identifying patients at elevated risk for these infections preoperatively could facilitate efforts to reduce infection rates. The objectives of this study were to estimate the incidence of postoperative S. aureus infections in cardiac surgery patients, to identify preoperative risk factors for these infections, and to establish a patient risk profile by means of data available to clinicians prior to surgery., Design: Cohort study., Setting: Eight medical centers that participate in the Society of Thoracic Surgeons National Cardiac Database., Patients: Patients who were undergoing elective cardiac surgery during the period January 1, 2000 through December 31, 2004., Methods: Clinical and microbiological data from 16,386 patients were combined. Multivariable stepwise logistic regression analysis was performed to predict S. aureus infection, which was defined by culture results., Results: Of the 16,386 patients, 205 (1.3%) developed S. aureus bloodstream or chest wound infection within 90 days after surgery. On multivariable analysis, bootstrap-validated preoperative risk factors for S. aureus bloodstream or chest wound infection included a body mass index greater than 40 (adjusted odds ratio [aOR], 1.9 [95% confidence interval {CI}, 1.1-3.2]), chronic renal failure (aOR, 1.8 [95% CI, 1.1-2.9]), and chronic lung disease (aOR, 1.4 [95% CI, 1.0-2.0]). Only 8 patients had all 3 risk factors., Conclusions: Although preoperative risk factors can be easily identified, the majority of patients who developed S. aureus infections after cardiac surgery did not have any risk factors. Preventive measures should not be restricted to a select group of cardiac surgery patients and should rather address the entire patient population.

Background: Bloodstream infections (BSIs) caused by Candida glabrata have increased substantially. Candida glabrata is often associated with resistance to fluconazole therapy. However, to our knowledge, risk factors for fluconazole-resistant C glabrata BSIs have not been studied., Methods: A case-case-control study was conducted at 3 hospitals from January 1, 2003, to May 31, 2007. The 2 case groups included patients with fluconazole-resistant C glabrata BSIs (minimum inhibitory concentration > or =16 microg/mL) and patients with fluconazole-susceptible C glabrata BSIs (minimum inhibitory concentration < or =8 microg/mL). Hospitalized patients without C glabrata BSIs were randomly selected for inclusion in the control group and were frequency matched to cases on the basis of time at risk. Two case-control studies were performed using this shared control group. The primary risk factor of interest, previous fluconazole use, was evaluated at multivariate analyses, adjusting for demographic data, comorbid conditions, and antimicrobial exposures., Results: We included 76 patients with fluconazole-resistant C glabrata BSIs, 68 patients with fluconazole-susceptible C glabrata BSIs, and 512 control patients. Previous fluconazole use (adjusted odds ratio [95% confidence interval], 2.3 [1.3-4.2]) and linezolid use (4.6 [2.2-9.3]) were independent risk factors for fluconazole-resistant C glabrata BSIs; previous cefepime use (2.2 [1.2-3.9]) and metronidazole use (2.0 [1.1-3.5]) were independent risk factors for fluconazole-susceptible C glabrata BSIs., Conclusions: Previous fluconazole use is a significant risk factor for health care-associated fluconazole-resistant C glabrata BSIs. Future studies will be needed to evaluate the effect of decreasing fluconazole use on rates of fluconazole-resistant C glabrata BSIs.

Objective: The prevalence of fluoroquinolone (FQ) resistance in Escherichia coli has increased markedly in recent years. Despite the important role of gastrointestinal tract colonization with FQ-resistant E. coli (FQREC), the prevalence of and risk factors for FQREC colonization among the general hospitalized patient population have not been described, to our knowledge. The objective of this study was to identify the prevalence of and risk factors for FQREC colonization among hospitalized patients., Design: Three-year case-control study. Case patients (ie, all subjects with FQREC colonization) were compared with control patients (ie, all subjects without FQREC colonization)., Setting: Two large medical centers within an academic health system., Participants: All patients hospitalized at the 2 study hospitals., Main Outcome Measure: Three annual fecal surveillance surveys were conducted. All patients colonized with FQREC (levofloxacin minimum inhibitory concentration, >or=8 microg/mL) were identified., Results: Of the 774 subjects, 89 (11.5%) were colonized with FQREC. Although there was a significant association between prior FQ use and FQREC colonization on bivariable analysis (odds ratio [OR], 2.02 [95% confidence interval {CI}, 1.14-3.46]; P=.01), there was statistically significant effect modification by year of study (P=.005). In multivariable analyses, after controlling for the hospital and for the duration of hospitalization prior to sampling, the association between FQ use and FQREC colonization was as follows: adjusted OR (aOR), 0.97 (95% CI, 0.29-3.23) in 2002; aOR, 1.41 (95% CI, 0.57-3.50) in 2003; and aOR, 9.87 (95% CI, 3.67-26.55) in 2004., Conclusions: The association between prior FQ use and FQREC colonization varied significantly by study year, suggesting that the clinical epidemiology of resistant organisms may change over time. Furthermore, in the context of recent work showing significant changes in FQREC prevalence as well as changes in FQ resistance mechanisms (specifically, efflux overexpression) over the same time period, these results suggest a previously unrecognized complexity in the relationship between the clinical and molecular epidemiology of FQ resistance.

Coadministration of oral divalent or trivalent cation-containing compounds with oral fluoroquinolones may impair fluoroquinolone absorption. Among 3,134 patients who received a course of oral levofloxacin, coadministration was significantly associated with subsequent identification of a levofloxacin-resistant isolate. Strategies to curb the emergence of fluoroquinolone resistance should include avoiding the coadministration of divalent or trivalent cation-containing compounds and fluoroquinolone.

Of 49 subjects, 21 were colonized with more than one strain of Escherichia coli and 12 subjects had at least one strain present in fewer than 20% of colonies. The ability to accurately characterize E. coli strain diversity is directly related to the number of colonies sampled and the underlying prevalence of the strain.

We assessed the impact of free on-site influenza vaccination on childcare staff vaccination prevalence using 2 before-and-after studies. Vaccination was offered during the 2003-2004 and 2006-2007 influenza seasons. Staff vaccination prevalence was higher in each intervention season compared to the prior, nonintervention season. No baseline characteristics were associated with receipt of vaccination.

Purpose: The Infectious Diseases Society of America and US CDC recommend 60 days of ciprofloxacin, doxycycline, or amoxicillin for anthrax prophylaxis. It is not possible to determine severe adverse drug event (ADE) risks from the few people thus far exposed to anthrax prophylaxis. This study's objective was to estimate risks of severe ADEs associated with long-term ciprofloxacin, doxycycline, and amoxicillin exposure using three large databases: one electronic medical record (General Practice Research Database) and two claims databases (UnitedHealthcare, HMO Research Network)., Methods: We include office visit, hospital admission and prescription data for 1/1/1999-6/30/2001. Exposure variable was oral antibiotic person-days (pds). Primary outcome was hospitalization during exposure with ADE diagnoses: anaphylaxis, phototoxicity, hepatotoxicity, nephrotoxicity, seizures, ventricular arrhythmia, or infectious colitis., Results: We randomly sampled 999,773, 1047,496, and 1819,004 patients from Databases A, B, and C respectively. 33,183 amoxicillin, 15,250 ciprofloxacin and 50,171 doxycycline prescriptions continued > or =30 days. ADE hospitalizations during long-term exposure were not observed in Database A. ADEs during long-term amoxicillin were seen only in Database C with 5 ADEs or 1.2(0.4-2.7) ADEs/100,000 pds exposure. Long-term ciprofloxacin showed 3 and 4 ADEs with 5.7(1.2-16.6) and 3.5(1.0-9.0) ADEs/100,000 pds in Databases B and C, respectively. Only Database B had ADEs during long-term doxycycline with 3 ADEs or 0.9(0.2-2.6) ADEs/100,000 pds. For most events, the incidence rate ratio, comparing >28 versus 1-28 pds exposure was <1, showing limited evidence for cumulative dose-related ADEs from long-term exposure., Conclusions: Long-term amoxicillin, ciprofloxacin, and doxycycline appear safe, supporting use of these medications if needed for large-scale post-exposure anthrax prophylaxis.

We assessed the rate of recovery of fluoroquinolone-resistant and fluoroquinolone-susceptible Escherichia coli isolates from culture of frozen perirectal swab samples compared with the results for culture of the same specimen before freezing. Recovery rates for these 2 classes of E. coli were 91% and 83%, respectively. The majority of distinct strains recovered from the initial sample were also recovered from the frozen sample. The strains that were not recovered were typically present only in low numbers in the initial sample. These findings emphasize the utility of frozen surveillance samples.

The effects of contact isolation on patient satisfaction are unknown. We performed a cross-sectional survey and found that most patients lack education and knowledge regarding isolation but feel that it improves their care. In multivariable analysis, isolated patients were not less satisfied with inpatient care than were nonisolated patients.

Health care-acquired infections present a tremendous challenge to the care of hospitalized patients. Unfortunately, the risk of acquiring a health care-associated infection (HAI) is rising. The vast majority of HAI are of four types: urinary tract infections, surgical site infections, bloodstream infections, and pneumonia. This chapter aims to provide current data and strategies relating to the prevention of HAIs among hospitalized patients.

Background: A number of recent studies of antimicrobial resistance have focused on the role of antimicrobial-resistant pathogens that colonize the gastrointestinal tract. However, participation rates have been low in studies that involve fecal sampling. Attitudes toward such studies among potential study participants have not been assessed., Methods: We conducted a cross-sectional survey, enrolling 3 groups of inpatients from a large academic center. Group 1 consisted of patients who had previously participated in a cohort study of fluoroquinolone-resistant Escherichia coli, which involved the collection of perirectal swab samples. Group 2 consisted of patients who had previously refused to participate in the study of fluoroquinolone-resistant E. coli. Group 3 consisted of patients who had never been asked to participate in the study of the fluoroquinolone-resistant E. coli. The survey assessed patients' attitudes and beliefs regarding medical research and their willingness to consent to collection of a perirectal swab sample. Response options were recorded on a 5-point Likert scale. The Fisher exact test was used to compare dichotomized responses across study groups., Results: A total of 90 patients were surveyed: there were 29 in group 1 and in group 2 and 32 in group 3. Of 90 patients, 31 (35%) believed researchers might run additional tests on collected samples without informing the patient, whereas 25 (27%) believed persons other than the research team might gain access to study results. The belief that a person could get sicker as a result of a having a perirectal swab sample collected was significantly more common among patients who had previously refused to participate in the fluoroquinolone-resistant E. coli study., Conclusion: This study highlights important beliefs and attitudes that are associated with the likelihood of participating in studies of antimicrobial resistance. Explicitly addressing these concerns with eligible patients is critical to optimize participation in future studies.

Background: Analytic approaches to the identification of risk factors for the development of drug resistance vary and may affect study results. Using fluroquinolone-resistant Pseudomonas aeruginosa (FQRPA) and imipenem-resistant P. aeruginosa as models (IRPA), we aimed to examine the effect of different approaches to classification of prior antibiotic use (i.e., class versus spectrum) on the identification of risk factors for antibiotic resistance., Methods: Case-control studies to identify risk factors for FQRPA and IRPA were performed. In each, two analytic models were utilized. In the first, prior antibiotic use was classified by class, and in the other, prior antibiotic use was classified by spectrum of activity. Risk factors identified by the two models were compared qualitatively for each resistant organism., Results: 879 isolates of P. aeruginosa were included in the case-control studies. Risk factors for FQRPA and IRPA identified in multivariable analyses differed based on which method of classification of prior antibiotic use was utilized., Conclusions: The identification risk factors for the development of drug-resistant organisms could depend on the method of classification of prior antibiotic use. In studies of risk factors for resistant infections, the approach to classification of prior antibiotic use should be clearly stated and justified.

Purpose: Infections caused by drug-resistant gram-negative bacteria are a growing threat to the healthcare community and clinicians are encouraged to employ a combination of strategies for effective prevention and treatment of these difficult infections., Summary: Recent epidemiological studies suggest an increase in healthcare- associated infections caused by gram-negative bacteria, particularly Klebsiella spp., Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter spp. The rising incidence of drug resistance of these pathogens presents a challenge given the few novel antimicrobial agents under development that specifically target these organisms. To combat this trend, recent guidelines promote Antimicrobial Stewardship Programs (ASP) as an effective means to possibly control the emergence and spread of antimicrobial resistance. Two key ASPs strategies include prospective audit, intervention, and feedback, and formulary restriction and preauthorization. The best methods to measure antimicrobial use and antimicrobial resistance are still being developed. In addition, using pharmacokinetics and pharmacodynamics priniciples to guide antimicrobial dosing regimens may have a role in controlling development of resistance. Finally, enforcing rigorous infection control practices can reduce the transmission of problematic pathogens within the healthcare setting., Conclusion: With a limited number of antimicrobial agents in development, clinicians cannot rely on new drugs alone to treat infections due to drug-resistant gram-negative bacteria but must also incorporate strategies that reduce the emergence of resistance and prevent the spread of problematic bacteria. Potentially effective interventions include antimicrobial stewardship tactics that advocate optimal use of currently available antimicrobial agents and rigorous infection control measures. Infectious diseases trained pharmacists are in a unique position to play a key role in helping control the spread of nosocomial pathogens.

We examined the possible unintended consequences of a 72-hour automatic order to discontinue vancomycin therapy in an antimicrobial stewardship program (ASP). Of 120 patients, 11 had vancomycin therapy discontinued at 72 hours without a call to the ASP, and 7 experienced a treatment interruption of 6-36 hours. All discontinuation of therapy was considered appropriate, and the 7 treatment interruptions did not have clear clinical consequences. Only one-third of patients had ASP stickers that warned of impending discontinuation of vancomycin therapy placed appropriately in the medical record.

Objectives: Although many studies have explored the association between antimicrobial use and antimicrobial resistance, definitions of "exposure" (i.e., prior antimicrobial use) differ across such studies. Specifically, it has been noted that some studies define "exposure" as any antimicrobial use, while others require the administration of at least 24 or 48 h of an antimicrobial to constitute "exposure." The impact of different definitions of exposure on final study results is unknown. We conducted the current study to determine the impact of varying the minimum threshold of prior antimicrobial use to define exposure status in studies of antimicrobial resistance., Methods: We used a dataset from a prior study of risk factors for fluoroquinolone (FQ) resistant Pseudomonas aeruginosa (FQRPA) to address the study aim. Four separate multivariable models of risk factors for FQRPA were built. Each model defined a different threshold for the duration of antimicrobial administration to determine "exposure" to that antimicrobial: (1) no threshold (i.e., a subject is considered exposed if any use of the antimicrobial was documented); (2) >24 h of use of the antimicrobial is necessary to be considered exposed; (3) >48 h of use is required; and (4) >72 h of use is required. Except for these definitions, the four multivariable models were built in exactly the same way, each using prior FQ use as the primary risk factor of interest., Results: Among 872 P. aeruginosa isolates included in the original dataset, 332 (38.2%) were FQ-resistant. Each of the four multivariable models identified prior FQ use as an independent risk factor for FQRPA. However, as increasingly strict thresholds were used, the association between FQ use and FQRPA increased. Furthermore, prior use of an agent with activity against anaerobic bacteria was associated with FQRPA in models 2, 3 and 4, but not in model 1., Conclusions: The use of different thresholds to define prior "exposure" to antimicrobials altered the associations between antimicrobial use and resistance. Stricter thresholds resulted in a higher estimate of the association between antimicrobial use and resistance. Furthermore, different risk factors may be identified depending on how exposure is defined. Greater attention to this issue is necessary to optimize identification of modifiable risk factors for resistance as well as accurately compare results across studies.

We conducted a retrospective cohort study of children with catheter-associated bloodstream infections (BSIs) due to Escherichia coli and/or Klebsiella. Risk factors for poor outcome (ie, death or recurrence of infection) were receipt of mechanical ventilation (adjusted odds ratio [aOR], 4.6 [95% confidence interval {CI}, 1.39-16.30]) and receipt of total parenteral nutrition (aOR, 3.5 [95% CI, 1.1-10.8]). A significant proportion of children with catheter-associated BSI were treated successfully without catheter removal.

Objective: To identify risk factors for infection or colonization with aztreonam-resistant Pseudomonas aeruginosa and examine the impact of this organism on mortality., Design: A case-control study was performed to identify risk factors for infection or colonization with aztreonam-resistant P. aeruginosa. A cohort study was subsequently performed to examine the impact of aztreonam resistance on outcomes., Setting: A tertiary referral center in southeastern Pennsylvania.Participants. Inpatients with a clinical culture positive for P. aeruginosa between January 1, 1999, and December 31, 2000., Results: Of 720 P. aeruginosa. isolates, 183 (25.4%) were aztreonam-resistant and 537 (74.6%) were aztreonam susceptible. In a multivariable model, prior fluoroquinolone use (adjusted odds ratio [aOR], 1.81 [95% confidence interval {CI}, 1.17-2.80]), prior use of an antianaerobic agent (aOR, 1.56 [95% CI, 1.06-2.29]), and renal insufficiency (aOR, 1.59 [95% CI, 1.10-2.29]) were associated with infection or colonization with aztreonam-resistant P. aeruginosa, while older age (aOR, 0.98 [95% CI, 0.97-0.99] per year of age) was negatively associated with infection or colonization with this organism. In-hospital mortality was higher among subjects infected or colonized with aztreonam-resistant P. aeruginosa, compared with those who were infected or colonized with aztreonam-susceptible P. aeruginosa (25.7% vs 16.8%; P=.009), but in multivariable analysis, no significant association was found between infection or colonization with aztreonam-resistant P. aeruginosa and mortality., Conclusions: Curbing the use of fluoroquinolones and antimicrobials with antianaerobic activity may be an effective strategy to limit the emergence of aztreonam-resistant P. aeruginosa.

Objective: A prior study suggested that antidepressants might increase the risk of hospitalization for pneumonia in the elderly. This study sought to confirm or refute this hypothesis., Study Design and Setting: Case-control study of persons aged 65 and above nested in the UK General Practice Research Database., Results: We identified 12,044 cases of the hospitalization for pneumonia (the primary outcome) and 48,176 controls. The odds ratio (OR) for any antidepressant use, adjusting for age, sex, and calendar year was 1.61 (95% confidence interval 1.46-1.78). After further adjustment for comorbidity measures, the OR was 0.89 (0.79-1.00). We also identified 159 cases of hospitalization for aspiration pneumonia (the secondary outcome) and 636 controls. The OR for any antidepressant use, adjusted for age, sex, and calendar year was 1.45 (0.65-3.24). After further adjustment for comorbidity measures, the OR was 0.63 (0.23-1.71)., Conclusion: These findings refute the prior hypothesis that use of antidepressants by elderly patients increases the risk of hospitalization for pneumonia or for aspiration pneumonia. Decisions regarding use of antidepressants in elderly persons should not be affected by concern about pneumonia risk. Data-derived hypotheses should be independently confirmed before being acted upon.

Background: Mediastinitis is a devastating complication of pediatric cardiothoracic surgery. However, risk factors for the development of mediastinitis are poorly characterized. The objective of this study was to identify risk factors for mediastinitis in a cohort of children undergoing cardiothoracic surgery at a tertiary care children's hospital., Methods: This case-control study included patients who underwent median sternotomy between January 1, 1995 and December 31, 2003. Univariate analyses, logistic regression, and multinomial regression were performed to determine the association between potential risk factors and the development of mediastinitis., Results: Forty-three patients with mediastinitis and 184 patients without mediastinitis were included. One hundred and twelve (49%) patients were female. The median patient age was 128 days (interquartile range: 7 days-2.0 years). A known or possible genetic syndrome was present in 53 (24%) patients. The following factors were associated with the development of mediastinitis: presence of a known or possible genetic syndrome (adjusted odds ratio, OR: 4.5; 95% confidence interval, CI: 1.8-11.4); American Society of Anesthesiologists score >3 (adjusted OR: 3.4; 95% CI: 1.1-10.3); and presence of intracardiac pacing wires for >3 days (adjusted OR: 15.8; 95% CI: 2.0-127.2)., Conclusions: The presence of a known or possible genetic syndrome, American Society of Anesthesiologists score >3, and the presence of intracardiac pacing wires for >3 days were each associated with the development of mediastinitis in children after median sternotomy.

The ability to recover bacteria from frozen culture specimens has important implications. The purpose of this study was to validate the utility of frozen specimens for recovery of several gram-positive and gram-negative bacterial species by culture. Results demonstrate that 98% of 250 bacterial isolates identified on initial culture were subsequently recovered by culture of frozen specimens after a median storage period of 564 days.

Background: In studies of the association between antibiotic-resistant infection and mortality, the importance of controlling for the underlying severity of illness is well recognized. However, it is unclear when the severity of illness should be assessed. Controlling for severity of illness on the day the culture specimen is obtained may underestimate the true association between resistance and mortality., Objective: To assess the impact of calculating the Acute Physiology and Chronic Health Evaluation (APACHE) II score at different time points on the association between antimicrobial resistance and mortality., Methods: We used an existing data set from a study that investigated the association between fluoroquinolone resistance and mortality. The APACHE II score was calculated at 3 time points: the day the culture specimen was obtained, 1 day before the culture specimen was obtained, and 2 days before the culture specimen was obtained. Separate multivariable models were constructed using the 3 different APACHE II scores. These models were compared qualitatively., Results: Of 91 total subjects, 51 were infected with a fluoroquinolone-resistant strain and 40 with a fluoroquinolone-susceptible strain. The median APACHE II score for all subjects was 13 (95% confidence interval [CI], 11-15) when calculated on the day the culture specimen was obtained, 12 (95% CI, 11-13) when calculated 1 day before, and 11 (95% CI, 10-13) when calculated 2 days before the culture specimen was obtained. Of 91 subjects, 12 (13.2%) died. The 3 multivariable models (each with the APACHE II score calculated on a different day) were not substantively different; the adjusted odds ratio for the association between fluoroquinolone-resistant infection and mortality varied only from 1.38 to 1.65 in the 3 models., Conclusions: APACHE II scores calculated at different time points relative to obtainment of the culture specimen did not differ substantively. Furthermore, when the adjusted association between fluoroquinolone resistance and mortality was assessed, there were no substantive differences across multivariable models that incorporated APACHE II scores calculated at different time points.

Objective: Many studies have investigated the association between prior antibiotic use and antibiotic resistance. However, methods used in past studies to describe the extent of prior antibiotic use (eg, use of the 2 categories exposure versus no exposure and measurement of duration of exposure) have not been reviewed. The impact of the use of different methods for quantifying the use of antibiotics is unknown. The objectives of this study were to characterize past approaches to describing the extent of antibiotic use and to identify the impact of the use of different methods on associations between use of specific antibiotics and infection with an antibiotic-resistant-organism., Methods: We conducted a systematic review of studies that investigated risk factors for extended-spectrum beta -lactamase (ESBL)-producing Escherichia coli and Klebsiella species to identify variability in past approaches to describing the extent of antibiotic use. We then reanalyzed a data set from a prior study of risk factors for infection with ESBL-producing E. coli and Klebsiella species. We developed 2 separate multivariable models: 1 in which prior antibiotic use was described as a categorical variable (eg, exposure or no exposure) and 1 in which antibiotic use was described as a continuous variable (eg, measured in antibiotic-days). These models were compared qualitatively., Setting: Large academic medical center., Results: The 25 articles included in the systematic review revealed a variety of methods used to describe the extent of prior antibiotic exposure. Only 1 study justified its approach. Results from the 2 multivariable models that used different methodologic approaches differed substantially. Specifically, use of third-generation cephalosporins was a risk factor for infection with ESBL-producing E. coli and Klebsiella species when antibiotic use was described as a continuous variable but not when antibiotic use was described as a categorical variable., Conclusions: There has been no consistent method for assessing the extent of prior antibiotic exposure. The use of different methods may substantially alter the identified antimicrobial risk factors, which has important implications for the resultant interventions regarding antimicrobial use.

Objective: Prior-approval antimicrobial stewardship programs (ASPs) improve patient outcomes and decrease antimicrobial resistance. These benefits would be limited if physicians circumvented ASP efforts. We evaluated whether prescribers wait until after the prior-approval period to order restricted antimicrobial therapy that is in conflict with guidelines or unnecessary., Design: A cross-sectional study design and a retrospective cohort study design., Setting: A tertiary care, academic medical center with a prior-approval ASP that was active between 8 am and 10 pm., Methods: We evaluated whether there was an increase in the proportion of orders for antimicrobial therapy that involve restricted (vs nonrestricted) antimicrobials during the first hour that the ASP is inactive (ie, the first hour that prior approval is not required), compared with the remainder of the day. We also evaluated whether restricted antimicrobial therapy ordered during this first hour is less likely to be continued when the ASP becomes active the next day, compared with that ordered during the preceding hour., Results: A greater proportion of the antimicrobial therapy orders placed between 10:00 pm and 10:59 pm were for restricted agents, compared with orders placed during other periods (57.0% vs 49.9%; P=.02). Surgical patients for whom antimicrobial therapy orders were placed between 10:00 pm and 10:59 pm were less likely to have that antimicrobial therapy continued, compared with patients whose therapy was ordered between 9:00 pm and 9:59 pm (60.0% vs 98.1%; P<.001). Nonsurgical patients whose therapy orders were placed between 10:00 pm and 10:59 pm were also less likely to have the ordered antimicrobial therapy continued, compared with patients whose therapy was ordered between 9:00 pm and 9:59 pm (70.8% vs 84.2%; P=.01)., Conclusion: Physicians avoid having to obtain prior approval for therapy involving restricted antimicrobials by waiting until restrictions are no longer active to place orders. Compared with restricted antimicrobial therapy ordered when the ASP is active, these courses of therapy are less often continued by the ASP, suggesting that they are more likely to be in conflict with guidelines or unnecessary.

Objective: To determine whether the National Nosocomial Infections Surveillance (NNIS) System risk index adequately stratified a population of pediatric patients undergoing cardiac surgery according to the risk of developing surgical site infection (SSI)., Design: A retrospective, case-control study., Setting: An urban tertiary care children's hospital., Patients: Patients who had a median sternotomy performed between January 1, 1995, and December 31, 2003, were eligible for inclusion in the study. For all case patients, medical records were reviewed to verify that all patients met the case definition for SSI. Control subjects were chosen randomly from among all patients who underwent median sternotomy during the study period who did not develop SSI., Results: Thirty-eight patients with SSI and 172 patients without SSI were included. One hundred six patients (50%) were male. The median patient age was 4 months. The sensitivity of the NNIS risk index with cutoff scores of 0 to 1 and 2 to 3 was 20%. The distribution of patients with SSI for an NNIS risk index score of 0 was 0%; for a score of 1, 80%; for a score of 2, 20%; and for a score of 3, 0%. The distribution of patients without SSI for a scores of 0 was 4%; for a score of 1, 87%; for a score of 2, 9%; and for a score of 3, 0%. The area under the receiver-operating characteristic curve (AUC) of the original NNIS risk index was 0.57. The modified risk indices did not perform significantly better, with an AUC range of 0.58 to 0.73., Conclusions: The NNIS risk index did not adequately stratify pediatric patients undergoing median sternotomy according to their risk of developing an SSI. Various modifications to the risk index yielded only slightly higher AUC values.

Objectives: Postoperative bloodstream infections are a major source of morbidity and increased health care costs. In adults, mediastinitis has been described as a risk factor for bloodstream infections. The objectives of this retrospective cohort study were to determine the incidence and to identify risk factors for postoperative bloodstream infections among children after median sternotomy in an urban tertiary care children's hospital., Methods: For this study, 192 patients were randomly selected from among all patients undergoing median sternotomy between January 1, 1995, and December 31, 2003., Results: Ninety-eight (51%) of the 192 eligible patients were male. The median patient age was 5.4 months (interquartile range: 1 day-41.5 years). Bloodstream infections occurred in 12 (6.3%; 95% confidence interval [CI]: 3.3%-10.7%) patients within the first 30 days after median sternotomy. Bloodstream infections developed a median of 11 days (range: 3-29 days) after median sternotomy. Gram-negative bacilli caused 6 (50%) of the 12 bloodstream infections. Specific causes of bloodstream infections included Pseudomonas aeruginosa (n = 3), coagulase-negative staphylococci (n = 3), Pseudomonas fluorescens-putida (n = 2), Staphylococcus aureus (n = 2), Serratia marcescens (n = 1), and Candida albicans (n = 1). Multivariable analysis revealed that the development of mediastinitis (odds ratio [OR], 28.16; 95% CI, 3.37-235.22) and the requirement for postoperative extracorporeal membrane oxygenation (OR, 12.52; 95% CI, 2.99-52.41) were associated with bloodstream infections after median sternotomy., Conclusions: Postoperative bloodstream infections occurred in 6.3% of children undergoing median sternotomy. Postoperative mediastinitis and the requirement for extracorporeal membrane oxygenation were risk factors for bloodstream infections after median sternotomy. These findings warrant exploration in a larger, multicenter study.