Prior Fluoroquinolone Use Research Articles

Risk factors and clinical impact of multidrug resistance in healthcare-associated bacteraemic urinary tract infections: a post-hoc analysis of a multicentre prospective cohort in Spain

The global burden associated with antimicrobial resistance is of increasing concern. To evaluate risk factors associated with multidrug-resistant (MDR) infection and its clinical impact in a cohort of patients with healthcare-associated bacteraemic urinary tract infections (BUTIs). This was a prospective, multicentre, post-hoc analysis of patients with healthcare-associated-BUTI (ITUBRAS-2). The primary outcome was MDR profile. Secondary outcomes were clinical response (at 48-72h and at hospital discharge) and length of hospital stay from onset of BUTI. Logistic regression was used to evaluate variables associated with MDR profile and clinical response. Length of hospital stay was evaluated using multivariate median regression. In all, 443 episodes were included, of which 271 (61.17%) were classified as expressing an MDR profile. In univariate analysis, MDR profile was associated with E.coli episodes (odds ratio (OR): 3.13; 95% confidence interval (CI): 2.11-4.69, P < 0.001) and the extensively drug-resistant (XDR) pattern with P.aeruginosa aetiology (7.84; 2.37-25.95; P= 0.001). MDR was independently associated with prior use of fluoroquinolones (adjusted OR: 2.43; 95% CI: 1.25-4.69), cephalosporins (2.14; 1.35-3.41), and imipenem or meropenem (2.08; 1.03-4.20) but not with prior ertapenem. In terms of outcomes, MDR profile was not associated with lower frequency of clinical cure, but was associated with longer hospital stay. MDR profile was independently associated with prior use of fluoroquinolones, cephalosporins, imipenem, and meropenem, but not with prior ertapenem. MDR-BUTI episodes were not associated with worse clinical cure, although they were independently associated with longer duration of hospital stay.

Comparative Study between Operative and Non-Operative Management of Complete Achilles Tendon Rupture

ntroduction Achilles tendon rupture is the most common tendon rupture in the lower extremity. The injury most commonly occurs in adults in their third to fifth decade of life.[1] Acute ruptures often present with sudden onset of pain associated with a "snapping" or audible "pop" heard at the site of injury. Patients can describe the sensation of being kicked in the lower leg. The injury is causes significant pain and disability in patient populations. Achilles tendon injuries typically occur in individuals who are only active intermittently (i.e., the "weekend warrior" athletes). The injury is reportedly misdiagnosed as an ankle sprain in 20% to 25% of patients. Most commonly affected as 10% report a history of prodromal symptoms, and known risk factors include prior intratendinous degeneration, fluoroquinolone use, steroid injections, and inflammatory arthritides.[2,3]

Determining a urinary-specific antibiogram and risk factors of trimethoprim/sulfamethoxazole, ciprofloxacin and multidrug resistance among Enterobacterales in primary care.

Risk factors for ciprofloxacin or MDR in primary care urine specimens are not well defined. We created a primary care-specific antibiogram for Escherichia coli isolates from cases with complicated and uncomplicated urinary tract infection (UTI) and evaluated risk factors for ciprofloxacin, trimethoprim/sulfamethoxazole and MDR among Enterobacterales. We conducted a cross-sectional study to determine resistance and risk factors by collecting urine cultures from all patients (≥18 years) presenting with provider-suspected UTI at two primary care, safety-net clinics in Houston, TX, USA between November 2018 and March 2020. Among 1262 cultures, 308 cultures grew 339 uropathogens. Patients with Enterobacterales (n = 199) were mostly female (93.5%) with a mean age of 48.5 years. E. coli was the predominant uropathogen isolated (n = 187/339; 55%) and had elevated trimethoprim/sulfamethoxazole (43.6%) and ciprofloxacin (29.5%) resistance, low nitrofurantoin (1.8%) resistance, and no fosfomycin resistance. Among E. coli, 10.6% were ESBL positive and 24.9% had MDR. Birth outside the U.S.A., prior (2 year) trimethoprim/sulfamethoxazole resistance, and diabetes mellitus were associated with trimethoprim/sulfamethoxazole resistance. Prior (60 day) fluoroquinolone use, prior ciprofloxacin resistance and both diabetes mellitus and hypertension were strongly associated with ciprofloxacin resistance. Prior fluoroquinolone use and a history of resistance to any studied antibiotic were associated with MDR, while pregnancy was protective. We found elevated resistance to UTI-relevant antimicrobials and novel factors associated with resistance; these data can be incorporated into clinical decision tools to improve organism and drug concordance.

Outpatient antibiogram and predictors of ciprofloxacin and trimethoprim-sulfamethoxazole resistant urinary tract infections.

Context: Rising antibiotic resistance has transcended hospital boundaries and impacted individuals with community acquired urinary tract infections (UTI). Scant data on antibiotic resistance in outpatient settings exists and most studies in the United States (U.S.) have identified predictors of resistance in acute-care settings. Objective: Determine the antibiogram among Escherichia coli isolates and factors associated with ciprofloxacin and trimethoprim-sulfamethoxazole (TMP-SMX) resistant gram-negative urinary isolates. Study Design: Retrospective cohort study. Setting: Two primary care, safety-net clinics in Houston, TX between 11/2018 and 3/2020. Population studied: Patients aged 18 and older presenting with provider suspected uncomplicated or complicated UTI. Outcome measures: Resistance and predictors of resistance to UTI-relevant antibiotics. Results: Among 1265 cultures collected, 372 (28.4%) were positive. We detected E. coli (50.3%) and Group B Streptococcus (18.6%) most frequently. Our patient population consisted mostly of Hispanic (75.7%) females (92.5%) born outside the U.S. (67.3%) with a mean age of 47. Among patients with E. coli isolated (n=189), antibiotic resistance was highest to ampicillin (63%), TMP-SMX (44%), ciprofloxacin (31%), and cefazolin (30%); no or low resistance against amikacin (0%), fosfomycin (0%), and nitrofurantoin (2.7%) was detected. Approximately 12% of E. coli isolates were extended-spectrum beta-lactamase positive. Having a prior UTI caused by a TMP-SMX resistant gram-negative organism and being born outside the U.S increased the odds of TMP-SMX resistance by 3.71 (95% confidence interval: 1.6-9.2) and 3.08 (95% CI: 1.6-6.3), respectively. Having a complicated UTI (odds ratio (OR): 3.58; 95% CI: 1.1-12.1), prior fluoroquinolone use (OR: 6.81; 95% CI: 1.7-34.1) and a prior UTI with ciprofloxacin resistance (OR: 7.84; 95% CI: 3.2-20.7) increased the odds of having a ciprofloxacin resistance. Conclusion: The Infectious Disease Society of America cautions against prescribing an antibiotic if regional resistance exceeds 20%. We constructed an antibiogram and found resistance surpassed this threshold for TMP-SMX and ciprofloxacin and identified factors associated with resistance to these agents. Assessing these characteristics during clinical decision making may improve antibiotic-organism susceptibility concordance in primary care.

DOP73 Antibiotic use differentially affects the risk of antidrug antibody formation during anti-TNFα therapy in Inflammatory Bowel Disease

Abstract Background Anti-drug antibodies (ADA) to anti-TNF therapy drive loss of response to treatment. Links between intestinal microbial composition and response to anti-TNF therapy were demonstrated, and antibiotic use during anti-TNF therapy reduced the risk of ADA formation. Here, we aimed to assess the possible implications of specific antibiotic treatments on ADA formation in patients with inflammatory bowel disease (IBD) patients. Methods We performed a retrospective analysis of data from three health maintenance organizations, covering 89% of the Israeli population. All patients with IBD and available ADA levels were included. Survival analysis using Kaplan-Meier and multivariate Cox proportional hazards regression with drug use as time varying covariates methods were used to assess the association between specific antibiotic use and ADA development. C57BL and germ free mice were treated with respective antibiotics followed by immunization with infliximab. ADA were assessed after 14 days. Results We analyzed 1,946 patients treated with anti-TNF. Positive ADAs were detected in 363 patients (18.6%). Age, gender and concomitant use of immunomodulators where comparable in patients who eventually developed ADAs or not. However, infliximab and not adalimumab therapy, previous anti-TNF therapy and higher baseline C-reactive protein levels were significantly associated with ADA development in univariate analysis. Kaplan-Meier curves of prior antibiotic use demonstrated significant hazard of ADA development in patients who used cephalosporins or penicillins with beta-lactamase inhibitors (BLI) and reduced risk with prior use of fluoroquinolones, macrolides or metronidazole (Figure 1) with early risk divergence for most classes. Multivariable Cox proportional hazards model adjusted for multiple factors associated with ADA development was overall consistent with Kaplan-Meier estimates (Figure 2). In mice exposed to infliximab, increased ADA production by cefuroxime treatment and a non-significant reduction following azithromycin treatment was noticed (Figure 3). Germ free mice produced no ADA. Figure 1: Kaplan-Meier curves of cumulative risk of ADA development for prior use of specific antibiotics. P value for the log rank test is presented in each plot. Figure 2: Multivariable-adjusted HR with 95% CI of ADA for use of various antibiotic classes during anti-TNF therapy. Figure 3: Mean ADA levels in mice treated with anti-TNF and prior cefuroxime, azithromycin, or no antibiotic Conclusion ADA production is microbial dependent. The risk of ADA development during anti-TNF therapy can possibly be reduced by avoidance of cephalosporins and penicillins with BLI, or possibly reduced by treatment with fluoroquinolones or macrolides.

A Multi-Centered Case-Case-Control Study of Factors Associated With Klebsiella pneumoniae Carbapenemase-Producing Enterobacteriaceae Infections in Children and Young Adults.

Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae (KPC-CRE) are multidrug-resistant organisms causing morbidity and mortality worldwide. KPC-CRE prevalence is increasing in pediatric populations, though multi-centered data are lacking. Identifying risk factors for KPC-CRE infection in children and classifying genotypes is a priority in this vulnerable population. A case-case-control study of patients (0-22 years) at 3 tertiary-care Chicago-area medical centers, 2008-2015, was conducted. Case group 1 children possessed KPC-CRE infections; case group 2 harbored carbapenem-susceptible Enterobacteriaceae (CSE) infections; controls had negative cultures. Case-control matching was 1:1:3 by age, infection site and hospital. Statistical and molecular analyses were performed. Eighteen KPC-CRE infections were identified; median patient age was 16.5 years. Of 4 available KPC-CRE, 2 were unrelated, non-ST258 KP strains harboring blaKPC-2, one was a ST258 KP harboring blaKPC-3, and the last was an E. coli containing blaKPC-2. KPC-CRE and CSE-infected patients had more multidrug-resistant organisms infections, long-term care facility admissions and lengths of stay (LOS) > 7 days before culture. KPC-CRE and CSE patients had more gastrointestinal comorbidities (odds ratios [Ors], 28.0 and 6.4) and ≥ 3 comorbidities (Or 15.4 and 3.5) compared with controls; KPC-CRE patients had significantly more pulmonary and neurologic comorbidities (both ORs 4.4) or GI and pulmonary devices (ORs, 11.4 and 6.1). Compared with controls, CSE patients had more prior fluoroquinolone use (OR, 7.4); KPC-CRE patients had more carbapenem or aminoglycoside use (ORs, 10.0 and 8.0). Race, gender, LOS and mortality differences were insignificant. Pediatric patients with KPC-CRE infection suffer from high multi-system disease/device burdens and exposures to carbapenems and aminoglycosides. Different from adult reports, non-ST258 KP strains were more common, and LOS and mortality rates were similar in all groups. Pediatric CRE control in should focus on modifiable risk factors including antibiotic and device utilization.

Examining the epidemiology and microbiology of Clostridium difficile carriage in elderly patients and residents of a healthcare facility in southern Ontario, Canada

Whereas Clostridium difficile has been extensively studied in acute care facilities (ACFs), there is limited information about long-term care facilities (LTCFs), despite the high occurrence of putative risk factors (e.g. age, antimicrobial use, healthcare system contact). To evaluate C.difficile colonization in elderly patients and residents from one ACF and its associated LTCF. Stool swabs were collected from 884 LTCF and elderly (>65 years) hospital patients. Selective culture, polymerase chain reaction ribotyping and toxin gene characterization were performed. C.difficile was isolated from 92/410 (22.4%) ACF and 89/474 (18.8%) LTCF samples. Ribotypes 027 (35%) and 020 (10.4%) predominated in the LTCF whereas ribotypes AI-82/1 (20.7%) and ribotype O (14.1%) predominated at the ACF (P=0.031). In the LTCF, C.difficile colonization was associated with a history of proton pump inhibitor (PPI) use, and the interaction terms of male residents with prior medical leave of absence, and a prior history of C.difficile infection (CDI) combined with fluoroquinolone use. In the ACF, C.difficile colonization was associated with length of stay, feeding through a tube, antibiotic use, immunosuppressive therapy and VRE colonization, as well as the interaction terms for cephalosporin and fluoroquinolone use, prior CDI and cephalosporin use, and prior CDI and fluoroquinolone use. C.difficile colonization by ACF and LTCF residents was common, despite a low apparent incidence of CDI. The association with PPI provides further evidence of the potential importance of this widely used drug class in C.difficile colonization. Wide genetic diversity was present, highlighting the likelihood of multiple unidentified routes of C.difficile acquisition.

Epidemiology and risk factors of extensively drug-resistant Pseudomonas aeruginosa infections.

BackgroundThe incidence of nosocomial infections from extensively drug-resistant Pseudomonas aeruginosa (XDR-PA) has been increasing worldwide. We investigated the prevalence and factors associated with XDR-PA infections, including the factors that predict mortality.MethodsWe retrospectively studied a cohort of adult, hospitalized patients with P. aeruginosa (PA) infections between April and December 2014.ResultsOf the 255 patients with PA infections, 56 (22%) were due to XDR-PA, 32 (12.5%) to multidrug resistant Pseudomonas aeruginosa (MDR-PA), and 167 (65.5%) to non-MDR PA. Receiving total parenteral nutrition (adjusted OR [aOR] 6.21; 95% CI 1.05–36.70), prior carbapenem use (aOR 4.88; 95% CI 2.36–10.08), and prior fluoroquinolone use (aOR 3.38; 95% CI 1.44–7.97) were independently associated with the XDR-PA infections. All XDR-PA remained susceptible to colistin. Factors associated with mortality attributable to the infections were the presence of sepsis/septic shock (aOR 11.60; 95% CI 4.66–28.82), admission to a medical department (aOR 4.67; 95% CI 1.81–12.06), receiving a central venous catheter (aOR 3.78; 95% CI 1.50–9.57), and XDR-PA infection (aOR 2.73; 95% CI 1.05–7.08).ConclusionThe prevalence of XDR-PA infections represented almost a quarter of Pseudomonas aeruginosa hospital-acquired infections and rendered a higher mortality. The prompt administration of an appropriate empirical antibiotic should be considered when an XDR-PA infection is suspected.

Risk of gastrointestinal perforation in patients taking oral fluoroquinolone therapy: An analysis of nationally representative cohort.

BackgroundFluoroquinolone is a commonly prescribed antimicrobial agent, and up to 20% of its users registers adverse gastroenterological symptoms. We aimed to evaluate the association between use of fluoroquinolone and gastrointestinal tract perforation.MethodsWe conducted a nested case-control study on a national health insurance claims database between 1998 and 2011. The use of fluoroquinolones was classified into current (< 60 days), past (61–365 days prior to the index date) and any prior year use of fluoroquinolones. We used the conditional logistic regression model to estimate rate ratios (RRs), adjusting or matching by a disease risk score (DRS).ResultsWe identified a cohort of 17,510 individuals diagnosed with gastrointestinal perforation and matched them to 1,751,000 controls. Current use of fluoroquinolone was associated with the greatest increase in risk of gastrointestinal perforations after DRS score adjustment (RR, 1.90; 95% CI, 1.62–2.22). The risk of gastrointestinal perforation was attenuated for past (RR, 1.33; 95% CI, 1.20–1.47) and any prior year use (RR, 1.46; 95% CI, 1.34–1.59). To gain insights into whether the observed association can be explained by unmeasured confounder, we compared the risk of gastrointestinal perforation between fluoroquinolone and macrolide. Use of macrolide, an active comparator, was not associated with a significant increased risk of gastrointestinal perforation (RR, 1.11, 95%CI, 0.15–7.99). Sensitivity analysis focusing on perforation requiring in-hospital procedures also demonstrated an increased risk associated with current use. To mitigate selection bias, we have also excluded people who have never used fluoroquinolone before or people with infectious colitis, enteritis or gastroenteritis. In both of the analysis, a higher risk of gastrointestinal perforation was still associated with the use of fluoroquinolone.ConclusionsWe found that use of fluoroquinolones was associated with a non-negligible increased risk of gastrointestinal perforation, and physicians should be aware of this possible association.

Pseudomonas aeruginosa bacteraemia in patients with hematologic malignancies: risk factors, treatment and outcome

Our aims were to identify factors associated with Pseudomonas aeruginosa (PA) bloodstream infection (BSI) in patients with hematological malignancies and evaluate the outcome of the affected patients. Consecutive patients with hematological malignancies who developed PA BSI were identified. Subsequently, two case–control studies were performed to evaluate the risk factors (i) for PA BSI and (ii) for carbapenem resistant (CR) PA BSI. Patients' outcome was evaluated at 28 days after the onset of bacteraemia. A total of 64 patients with PA BSI (45 caused by CS and 19 by CR organisms) and 128 without PA BSI were enrolled. Patients with rapidly fatal disease, steroid use, neutropenia or prior surgery were more likely to develop PA BSI, whereas patients with previous hospitalization and prior use of fluoroquinolones were more likely to develop CR PA BSI. The 28-day mortality rate was 35.9%. Severity of sepsis was the only independent predictor of adverse outcome.

Application of Fluoroquinolone Resistance Score in Management of Complicated Urinary Tract Infections.

The fluoroquinolone resistance score (FQRS) predicts the probability of fluoroquinolone resistance with good discrimination. The score has been derived from patients with bloodstream infections caused by Gram-negative bacteria and is based on fluoroquinolone use within the past 6 months, among other clinical and health care exposure criteria. This study aims to examine the utility of the FQRS in patients with complicated urinary tract infections (cUTI) and determine whether extension of prior fluoroquinolone use to 12 months improves model discrimination. Adults with cUTI at Palmetto Health in central South Carolina, USA, from 1 April 2015 through 31 July 2015 were prospectively identified. Multivariate logistic regression was used to examine the association between prior fluoroquinolone use and resistance. Among 238 patients, 54 (23%) had cUTI due to fluoroquinolone-resistant bacteria. Overall, the median age was 66 years, 162 (68%) patients were women, and 137 (58%) patients had cUTI due to Escherichia coli Prior exposure to fluoroquinolones within 3 months (adjusted odds ratio [aOR], 23.4; 95% confidence interval [CI], 8.2 to 76.8; P < 0.001) and within 3 to 12 months (aOR, 13.2; 95% CI, 3.1 to 68.4; P < 0.001) was independently associated with fluoroquinolone resistance compared to no prior use. The area under the receiver operating characteristic curve for the FQRS increased from 0.73 to 0.80 when prior fluoroquinolone use was extended from 6 to 12 months. FQRSs of ≥2 and ≥3 had negative predictive values of 91% and 90%, respectively. The modified FQRS stratifies patients with cUTI on the basis of the predicted probability of fluoroquinolone resistance with very good discrimination. Application of the modified FQRS may improve antimicrobial utilization in patients with acute pyelonephritis.

Risk Factors, Outcomes, and Mechanisms of Tigecycline-Nonsusceptible Klebsiella pneumoniae Bacteremia.

A rise in tigecycline resistance in Klebsiella pneumoniae has been reported recently worldwide. We sought to identify risk factors, outcomes, and mechanisms for adult patients with tigecycline-nonsusceptible K. pneumoniae bacteremia in Taiwan. We conducted a matched case-control study (ratio of 1:1) in a medical center in Taiwan from January 2011 through June 2015. The cases were patients with tigecycline-nonsusceptible K. pneumoniae bacteremia, and the controls were patients with tigecycline-susceptible K. pneumoniae bacteremia. Logistic regression was performed to evaluate the potential risk factors for tigecycline-nonsusceptible K. pneumoniae bacteremia. Quantitative reverse transcription-PCR was performed to analyze acrA, oqxA, ramA, rarA, and kpgA expression among these isolates. A total of 43 cases were matched with 43 controls. The 14-day mortality of patients with tigecycline-nonsusceptible K. pneumoniae bacteremia was 30.2%, and the 28-day mortality was 41.9%. The attributable mortalities of tigecycline-nonsusceptible K. pneumoniae at 14 and 28 days were 9.3 and 18.6%, respectively. Fluoroquinolone use within 30 days prior to bacteremia was the only independent risk factor for tigecycline-nonsusceptible K. pneumoniae bacteremia. The tigecycline-nonsusceptible K. pneumoniae bacteremia was mostly caused by overexpression of AcrAB and/or OqxAB efflux pumps, together with the upregulation of RamA and/or RarA, respectively. One isolate demonstrated isolated overexpression of kpgA In conclusion, tigecycline-nonsusceptible K. pneumoniae bacteremia was associated with high mortality, and prior fluoroquinolone use was the independent risk factor for the acquisition of tigecycline-nonsusceptible K. pneumoniae The overexpression of AcrAB and/or OqxAB contributes to tigecycline nonsusceptibility in K. pneumoniae.

Risk factors and molecular epidemiology of community-onset, multidrug resistance extended-spectrum β-lactamase-producing Escherichia coli infections

Background/AimsAlthough multidrug resistance (MDR) among extended-spectrum β-lactamase-producing Escherichia coli (ESBL-EC) poses significant therapeutic challenges, little is known regarding the risk factors and epidemiology of community-onset MDR-ESBL-EC infections. We performed this study to investigate risk factors and the molecular epidemiology of community-onset MDR-ESBL-EC infections.MethodsWe conducted a case-control-control study of community-onset infections. MDR-ESBL-EC was defined as ESBL-EC that demonstrated in vitro resistance to trimethoprim-sulfamethoxazole, fluoroquinolones (FQs), and gentamicin. Patients with MDR-ESBL-EC infections were designated as case patients. A control group I (CG I) patient was defined as a person whose clinical sample yielded ESBL-EC that did not meet the criteria for MDR. A control group II (CG II) patient was defined as a patient with a non-ESBL-EC infection.ResultsOf 108 patients with ESBL-EC infections, 30 cases (27.8%) were due to MDR-ESBL-EC. Compared with CG I, prior use of FQs (odds ratio [OR], 3.16; 95% confidence interval [CI], 1.11 to 8.98) and immunosuppressant use (OR, 10.47; 95% CI, 1.07 to 102.57) were significantly associated with MDR-ESBL-EC. Compared with CG II, prior use of FQs (OR, 15.53; 95% CI, 2.86 to 84.27) and healthcare-associated infection (OR, 5.98; 95% CI, 2.26 to 15.86) were significantly associated with MDR-ESBL-EC. CTX-M-15 was the most common in MDR-ESBL-EC infections (59.1% [13/22]), while CTX-M-14 was the most common in non-MDR-ESBL-EC infections (41.6% [32/77]). CTX-M-15 was significantly associated with MDR-ESBL-EC (59.1% vs. 32.5%, p = 0.028). Pulsed-field gel electrophoresis showed clonal diversity of MDR-ESBL-EC isolates.ConclusionsThe emergence of strains of MDR-ESBL-EC in the community poses an important new public health threat. More information on the emergence and transmission of these strains will be necessary in order to prevent their spread.

Unique Risks and Clinical Outcomes Associated With Extended-Spectrum β-Lactamase Enterobacteriaceae in Veterans With Spinal Cord Injury or Disorder: A Case-Case-Control Study.

OBJECTIVES To describe the burden of extended-spectrum β-lactamase (ESBL) Enterobacteriaceae in veterans with spinal cord injury or disorder (SCI/D), to identify risk factors for ESBL acquisition, and to assess impact on clinical outcomes DESIGN Retrospective case-case-control study PATIENTS AND SETTING Veterans with SCI/D and utilization at a Veterans' Affairs medical center from January 1, 2012, to December 31, 2013. METHODS Patients with a positive culture for ESBL Klebsiella pneumoniae, Escherichia coli, or Proteus mirabilis were matched with patients with non-ESBL organisms by organism, facility, and level of care and to uninfected controls by facility and level of care. Inpatients were also matched by time at risk. Univariate and multivariate matched models were assessed for differences in risk factors and outcomes. RESULTS A total of 492 cases (62.6% outpatients) were matched 1:1 with each comparison group. Recent prior use of fluoroquinolones and prior use of third- and fourth-generation cephalosporins were independently associated with ESBL compared to the non-ESBL group (adjusted odds ratio [aOR], 2.61; 95% confidence interval [CI], 1.77-3.84; P<.001 for fluoroquinolones and aOR, 3.86; 95% CI, 2.06-7.25; P<.001 for third- and fourth-generation cephalosporins) and the control group (aOR, 2.10; 95% CI, 1.29-3.43; P = .003 for fluoroquinolones; and aOR, 3.31; 95% CI, 1.56-7.06; P=.002 for third- and fourth-generation cephalosporins). Although there were no differences in mortality rate, the ESBL group had a longer post-culture length of stay (LOS) than the non-ESBL group (incidence rate ratio, 1.36; 95% CI, 1.13-1.63; P=.001). CONCLUSIONS All SCI/D patients with ESBL were more likely to have had recent exposure to fluoroquinolones or third- and fourth-generation cephalosporins, and hospitalized patients were more likely to have increased post-culture LOS. Programs targeted toward reduced antibiotic use in SCI/D patients may prevent subsequent ESBL acquisition. Infect Control Hosp Epidemiol 2016;37:768-776.

Impact of Prostate-specific Antigen (PSA) Screening Trials and Revised PSA Screening Guidelines on Rates of Prostate Biopsy and Postbiopsy Complications

BackgroundProstate biopsy and postbiopsy complications represent important risks of prostate-specific antigen (PSA) screening. Although landmark randomized trials and updated guidelines have challenged routine PSA screening, it is unclear whether these publications have affected rates of biopsy or postbiopsy complications. ObjectiveTo evaluate whether publication of the 2008 and 2012 US Preventive Services Task Force (USPSTF) recommendations, the 2009 European Randomized Study of Screening for Prostate Cancer and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, or the 2013 American Urological Association (AUA) guidelines was associated with changes in rates of biopsy or postbiopsy complications, and to identify predictors of postbiopsy complications. Design, setting, and participantsThis quasiexperimental study used administrative claims of 5279315 commercially insured US men aged ≥40 yr from 2005 to 2014, of whom 104584 underwent biopsy. InterventionsPublications on PSA screening. Outcome measurements and statistical analysisInterrupted time-series analysis was used to evaluate the association of publications with rates of biopsy and 30-d complications. Logistic regression was performed to identify predictors of complications. Results and limitationsFrom 2005 to 2014, biopsy rates fell 33% from 64.1 to 42.8 per 100000 person-months, with immediate reductions following the 2008 USPSTF recommendations (−10.1; 95% confidence interval [CI], −17.1 to −3.0; p<0.001), 2012 USPSTF recommendations (−13.8; 95% CI, −21.0 to −6.7; p<0 .001), and 2013 AUA guidelines (−8.8; 95% CI, −16.7 to −0.92; p=0.03). Concurrently, complication rates decreased 10% from 8.7 to 7.8 per 100000 person-months, with a reduction following the 2012 USPSTF recommendations (−2.5; 95% CI, −4.5 to −0.45; p=0.02). However, the proportion of men undergoing biopsy who experienced complications increased from 14% to 18%, driven by nonsepsis infectious complications (p<0.001). Predictors of complications included prior fluoroquinolone use (odds ratio [OR]: 1.27; 95% CI, 1.22–1.32; p<0.001), anticoagulant use (OR: 1.14; 95% CI, 1.04–1.25; p=0.004), and age ≥70 yr (OR: 1.25; 95% CI, 1.15–1.36; p<0.001). Limitations included the retrospective design. ConclusionsAlthough there has been an absolute reduction in rates of biopsy and 30-d complications, the relative morbidity of biopsy continues to increase. These observations suggest a need to reduce the morbidity of biopsy. Patient summaryAbsolute rates of biopsy and postbiopsy complications have decreased following landmark publications about prostate-specific antigen screening; however, the relative morbidity of biopsy continues to increase.

Issue Highlights

Issue Highlights

Antibiotic pressure is a major risk factor for rectal colonization by multidrug-resistant Pseudomonas aeruginosa in critically ill patients.

The intestinal reservoir is central to the epidemiology of Pseudomonas aeruginosa, but the dynamics of intestinal colonization by different phenotypes have been poorly described. To determine the impact of antimicrobial exposure on intestinal colonization by multidrug-resistant (MDR) and extensively drug-resistant (XDR) P. aeruginosa, we screened intensive care unit (ICU) patients for rectal colonization on admission and at weekly intervals. During an 18-month study period, 414 ICU patients were enrolled, of whom 179 (43%) were colonized; 112 (63%) of these were identified at ICU admission and 67 (37%) during their ICU stay. At 10 days after ICU admission, the probabilities of carriage were 44%, 24%, and 24% for non-MDR, MDR-non-XDR, and XDR P. aeruginosa strains, respectively (log rank, 0.02). Pulsed-field gel electrophoresis showed 10 pairs of non-MDR P. aeruginosa and subsequent MDR-non-XDR strains isolated from the same patients to be clonally identical and another 13 pairs (8 MDR-non-XDR and 5 XDR) to be unrelated. There was one specific clone between the 8 MDR-non-XDR strains and an identical genotype in the 5 XDR isolates. The Cox regression analysis identified MDR P. aeruginosa acquisition as associated with the underlying disease severity (adjusted hazard ratio [aHR], 1.97; 95% confidence interval [CI], 1.22 to 3.18; P = 0.006) and prior use of fluoroquinolones (aHR, 1.02; 95% CI, 1.00 to 1.04; P = 0.039), group 2 carbapenems (aHR, 1.03; 95% CI, 1.00 to 1.07; P = 0.041), and ertapenem (aHR, 1.08; 95% CI, 1.02 to 1.14; P = 0.004). The epidemiology of MDR P. aeruginosa is complex, and different clusters may coexist. Interestingly, ertapenem was found to be associated with the emergence of MDR isolates.

Characteristics, risk factors and outcomes of adult cancer patients with extensively drug-resistant Pseudomonas aeruginosa infections.

To evaluate the characteristics and outcomes of cancer patients with extensively drug-resistant (XDR) Pseudomonas aeruginosa infections. This was a retrospective cohort of P. aeruginosa infections in cancer patients in Crete, Greece. Patients were followed until discharge. Mortality, predictors of mortality and risk factors for XDR P. aeruginosa infection were studied. Ninety seven episodes (89 patients) of P. aeruginosa infections (52 with bacteremia) were included in the study. In 22 cases, the infection was due to XDR isolates. All XDR isolates were susceptible to colistin and variably resistant to almost all other antibiotics. The multivariate analysis showed that the independent risk factors for XDR P. aeruginosa infection were hematologic malignancy (OR 40.7, 95 % CI 4.5-367.6) and prior fluoroquinolone use (OR 11.0, 95 % CI 2.0-60.5); lymphopenia was inversely associated with XDR infections (OR 0.16, 95 % CI 0.03-0.92). Mortality was 43 %; infection-related mortality was 24 %. Bacteremia (OR 8.47, 95 % CI 2.38-30.15), infection due to XDR isolates (OR 5.11, 95 % CI 1.15-22.62) and age (OR 1.05, 95 % CI 1.00-1.09) were independently associated with mortality. Mortality in cancer patients with P. aeruginosa infections was high. Infection due to XDR isolates was independently associated with mortality.

Antimicrobial Resistance in Pseudomonas sp. Causing Infections in Trauma Patients: A 6 Year Experience from a South Asian Country.

Drug resistance to Pseudomonas sp. has spread to such a level irrespective of the type of patients, that its pattern of distribution and antibiotic resistance needs to be studied in detail, especially in trauma patients and hence the study. A 6 year study was carried out among trauma patients to see the trend and type of resistance prevalent in the apex hospital for trauma care in India among nonduplicate isolates where multidrug-resistance (MDR), cross-resistance and pan-drug resistance in Pseudomonas sp. were analyzed. Of the total 2,269 isolates obtained, the species, which was maximally isolated was Pseudomonas aeruginosa (2,224, 98%). The highest level of resistance was seen in tetracycline (2,166, 95.5%, P < 0.001) and chloramphenicol (2,160, 95.2%, P < 0.001) and least in meropenem (1,739, 76.7%, P < 0.003). Of the total, 1,692 (74.6%) isolates were MDR in which P. aeruginosa (75%) were maximum. MDR Pseudomonas is slowing increasing since the beginning of the study period. Of 1,797 imipenem-resistant P. aeruginosa isolated during the study period, 1,763 (98%) showed resistance to ciprofloxacin or levofloxacin, suggesting that cross-resistance may have developed for imipenem due to prior use of fluoroquinolones. Antibiotic resistance in Pseudomonas sp. is fast becoming a problem in trauma patients, especially in those who requires prolong hospital stay, which calls for proper antimicrobial stewardship.

Risk factors of community-onset urinary tract infections caused by plasmid-mediated AmpC β-lactamase-producing Enterobacteriaceae

The AmpC β-lactamase (AmpC)-producing Enterobacteriaceae emerged worldwide. This study was conducted to determine the risk factors of community-onset urinary tract infections (UTIs) caused by plasmid-mediated AmpC-producing Enterobacteriaceae. Patients who were diagnosed as community-onset UTIs caused by Enterobacteriaceae in a tertiary-care teaching hospital from December 2010 to January 2012 were included. Extended-spectrum β-lactamase (ESBL)-producing isolates were excluded. We identified plasmid-mediated AmpC-producing Enterobacteriaceae both phenotypically (by disk potentiation test and double-disk synergy test) and genotypically (by Multiplex polymerase chain reaction (PCR) assay). The demographic data, clinical characteristics, and risk factors of acquisition were described. Among the 323 non-ESBL-producing Enterobacteriaceae identified in community-onset UTIs, 50 isolates were phenotypically positive for AmpC. Escherichia coli was the most common AmpC-producing organism (60%), followed by Klebsiella pneumonia (8%), and Enterobacter cloacae and Proteus mirabilis (6% for each species). The independent risk factors for acquisition of AmpC-producing Enterobacteriaceae included prior history of cerebral vascular accident [odds ratio (OR) = 2.014; 95% confidence interval (CI) = 1.007-4.031; p = 0.0048], and prior use of fluoroquinolones (OR = 4.049; 95% CI = 1.759-9.319; p = 0.001) and cephamycin (OR = 9.683; 95% CI = 2.007-45.135; p = 0.004). AmpC-producing isolates were multidrug resistant. Carbapenems, cefepime, and piperacillin/tazobactam had the best in vitro efficacy. The most commonly identified plasmid-mediated AmpC gene was bla(CIT), followed by bla(DHA)/bla(EBC), and bla(MOx). For community-onset UTIs, AmpC-producing Enterobacteriaceae should be suspected in those with prior history of cerebral vascular accident and prior use of antimicrobials. To treat these multiple-resistant isolates, carbapenems, cefepime, and piperacillin/tazobactam may be considered.