Rates Of Fluoroquinolone Resistance Research Articles

2291. Evaluation of Multidrug-Resistant Pseudomonas aeruginosa Isolates in Patients Receiving Ceftolozane/tazobactam

BackgroundMultidrug-resistant (MDR) Pseudomonas aeruginosa is a challenging pathogen to treat. Ceftolozane/tazobactam (C/T) is a combination cephalosporin and β-lactamase inhibitor that has demonstrated activity against MDR P. aeruginosa, including carbapenem-resistant isolates. The objective of this study was to evaluate multidrug resistance in P. aeruginosa isolates obtained from patients treated with C/T across the Veterans Affairs (VA) Healthcare System nationally.MethodsHospitalized patients who received at least 1 dose of CT between January 2015 and April 2018 and had a positive P. aeruginosa culture were included in this retrospective study. Culture source and antimicrobial susceptibility reports were assessed for each P. aeruginosa isolate. Isolates were categorized as multidrug-resistant based on the Centers for Disease Control (CDC) definition. Resistance rates were categorized by source of culture.ResultsWe identified 174 positive P. aeruginosa cultures among 154 patients who received at least one dose of C/T during the study period. The most common sources of isolates were lung (40% of patients), urine (21%), skin and soft tissue (15%), blood (14%), and bone/joint (14%). Most patients (98.1%) had isolates that were MDR, with high rates of carbapenem (84.4%), extended-spectrum cephalosporin (82.5%), and fluoroquinolone (79.9%) resistance. In this cohort, 50.6% of patients received at least one antibiotic prior to initiating C/T to which their clinical culture was not susceptible.ConclusionAntibiotic resistance was high in this cohort of patients with P. aeruginosa, and as a result, use of non-susceptible antibiotics occurred in 50.6% of patients before C/T was started. The high carbapenem resistance rates are of great clinical concern, but highlight an area of utilization for C/T given its activity against carbapenem-resistant P. aeruginosa.Disclosures All authors: No reported disclosures.

Changes in resistance among coliform bacteraemia associated with a primary care antimicrobial stewardship intervention: A population-based interrupted time series study.

BackgroundPrimary care antimicrobial stewardship interventions can improve antimicrobial prescribing, but there is less evidence that they reduce rates of resistant infection. This study examined changes in broad-spectrum antimicrobial prescribing in the community and resistance in people admitted to hospital with community-associated coliform bacteraemia associated with a primary care stewardship intervention.Methods and findingsSegmented regression analysis of data on all patients registered with a general practitioner in the National Health Service (NHS) Tayside region in the east of Scotland, UK, from 1 January 2005 to 31 December 2015 was performed, examining associations between a primary care antimicrobial stewardship intervention in 2009 and primary care prescribing of fluoroquinolones, cephalosporins, and co-amoxiclav and resistance to the same three antimicrobials/classes among community-associated coliform bacteraemia. Prescribing outcomes were the rate per 1,000 population prescribed each antimicrobial/class per quarter. Resistance outcomes were proportion of community-associated (first 2 days of hospital admission) coliform (Escherichia coli, Proteus spp., or Klebsiella spp.) bacteraemia among adult (18+ years) patients resistant to each antimicrobial/class. 11.4% of 3,442,205 oral antimicrobial prescriptions dispensed in primary care over the study period were for targeted antimicrobials. There were large, statistically significant reductions in prescribing at 1 year postintervention that were larger by 3 years postintervention when the relative reduction was −68.8% (95% CI −76.3 to −62.1) and the absolute reduction −6.3 (−7.6 to −5.2) people exposed per 1,000 population per quarter for fluoroquinolones; relative −74.0% (−80.3 to −67.9) and absolute reduction −6.1 (−7.2 to −5.2) for cephalosporins; and relative −62.3% (−66.9 to −58.1) and absolute reduction −6.8 (−7.7 to −6.0) for co-amoxiclav, all compared to their prior trends. There were 2,143 eligible bacteraemia episodes involving 2,004 patients over the study period (mean age 73.7 [SD 14.8] years; 51.4% women). There was no increase in community-associated coliform bacteraemia admissions associated with reduced community broad-spectrum antimicrobial use. Resistance to targeted antimicrobials reduced by 3.5 years postintervention compared to prior trends, but this was not statistically significant for co-amoxiclav. Relative and absolute changes were −34.7% (95% CI −52.3 to −10.6) and −63.5 (−131.8 to −12.8) resistant bacteraemia per 1,000 bacteraemia per quarter for fluoroquinolones; −48.3% (−62.7 to −32.3) and −153.1 (−255.7 to −77.0) for cephalosporins; and −17.8% (−47.1 to 20.8) and −63.6 (−206.4 to 42.4) for co-amoxiclav, respectively. Overall, there was reversal of a previously rising rate of fluoroquinolone resistance and flattening of previously rising rates of cephalosporin and co-amoxiclav resistance. The limitations of this study include that associations are not definitive evidence of causation and that potential effects of underlying secular trends in the postintervention period and/or of other interventions occurring simultaneously cannot be definitively excluded.ConclusionsIn this population-based study in Scotland, compared to prior trends, there were very large reductions in community broad-spectrum antimicrobial use associated with the stewardship intervention. In contrast, changes in resistance among coliform bacteraemia were more modest. Prevention of resistance through judicious use of new antimicrobials may be more effective than trying to reverse resistance that has become established.

High prevalence and diversity of tcdA-negative and tcdB-positive, and non-toxigenic, Clostridium difficile in Thailand

Studies on the prevalence and diversity of Clostridium difficile in Thailand have been limited to those derived from a few tertiary hospitals in Central Thailand. In this study, 145 C. difficile isolates collected in 13 provinces in Thailand during 2006–2018 were characterized by ribotyping and detection of toxin genes. Minimum inhibitory concentrations of eight antimicrobial agents were determined also for all 100 C. difficile strains collected from 2006 until 2015. Of the 145 strains of C. difficile, 71 (49%) were non-toxigenic, 46 (32%) were toxin A-negative, toxin B-positive (A-B+) and 28 (19%) were A+B+. No binary toxin-positive strain was found. The most common ribotype (RT) was RT 017 (A-B+CDT-, 19%, 28/145). Besides RT 017, 20 novel non-toxigenic and A-B+ ribotyping profiles, which may be related to RT 017 by the similarity of ribotyping profile, were identified. All C. difficile strains remained susceptible to metronidazole and vancomycin, however, a slight increase in MIC for metronidazole was seen in both toxigenic and non-toxigenic strains (overall MIC50/90 0.25/0.25 mg/L during 2006–2010 compared to overall MIC50/90 1.0/2.0 mg/L during 2011–2015). There was a high rate of fluoroquinolone resistance among RT 017 strains (77%), but there was little resistance among non-toxigenic strains. These results suggest that RT 017 is endemic in Thailand, and that the misuse of fluoroquinolones may lead to outbreaks of RT 017 infection in this country. Further studies on non-toxigenic C. difficile are needed to understand whether they have a role in the pathogenesis of C. difficile infection in Asia.

Increasing prevalence of the epidemic ribotype 106 in healthcare facility–associated and community-associated Clostridioides difficile infection

Clostridioides difficile is the leading cause of nosocomial diarrhea and antibiotics associated diarrhea, but it is also an increasingly common cause of community diarrhea. In recent years we have observed a progressive increase in the incidence of C. difficile infection (CDI) both at the hospital and community setting that could be explained by the dynamic epidemiology of C. difficile. The present study analyzes changes in the epidemiology of CDI for two years comparing healthcare facility–associated (HCFA) and community-associated (CA) CDI epidemiology, observed in a single laboratory setting. All new episodes of CDI diagnosed during the years 2015–2016 were included in the study and classified as HFCA-, CA- or indeterminate CDI. Isolates were characterized by ribotyping and antimicrobial susceptibility was also determined. A total of 272 primary episodes of different patients were included in the study and classified 55.5% as CA-, 32% as HO-HCFA, 6.25% as CO-HCFA and 6.25% as indeterminate CDI. Overall, ribotype 106 was the most prevalent and also, many patients who suffered recurrent episodes were associated with this ribotype (29%). In fact, ribotype 106 showed a significantly higher recurrence rate than other ribotypes (26% vs 11%, p = 0.03). Moreover, 46% of the moxifloxacin resistant isolates were ribotype 106. No significant differences of antimicrobial resistance were observed between HCFA- and CA-CDI isolates, although fluoroquinolone resistance rates were slightly higher in HCFA-CDI isolates (25% vs 18.5%), and fluoroquinolone resistant ribotypes 106 and 126 were more frequently associated to CA-CDI and ribotype 078 to HCFA-CDI. The increasing incidence of CDI in our health care area is partially explained by the growing prevalence of the epidemic ribotype 106, both in HFCA- and CA-CDI, probably favored by the higher resistance and recurrence rate associated to ribotype 106 isolates.

1457. Escherichia coli Community Acquired Pneumonia

Background Escherichia coli has been thought to be an uncommon cause of community-acquired pneumonia (CAP). Large epidemiological data on E. coli CAP (E-CAP) and its comparison to pneumococcal CAP (P-CAP) are lacking.MethodsA multi-center retrospective cohort study of adult patients (aged ≥ 18 years) admitted to 140 US hospitals with pneumonia and/or sepsis from 2010–2015, included in the Premier Research database. Patients with community-onset infection, antibiotic treatment beginning within the first 2 hospital days, and continued for at least 3 consecutive days were included. Patients were excluded if they had been transferred from another acute care facility, had cystic fibrosis, had a hospital length of stay of 1 day or less, co-existent urinary tract infection, gastrointestinal/ intra-abdominal infection, or simultaneous presence of other CAP pathogens. Pneumonia and sepsis were identified by ICD-9 codes.ResultsA total of 13,165 patients met the inclusion criteria, of which 1,247 had E. coli CAP. Majority of patients with E-CAP were nonnursing home residents (90.2%, 1,125/1,247). 69.3% (864/1,247) patients with E-CAP presented with”sepsis syndrome’ compared with only 48.1% in other Gram-negative CAP and 62.5% in P-CAP. Aspiration pneumonia was diagnosed in 5.9% (73/1,247) with E-CAP. Blood cultures were positive in 59.9% (748/1,247) of patients with E-CAP with 84.8% positivity in patients with sepsis syndrome. Patients with E-CAP compared with P-CAP were more likely to require ICU-level care (42.6% vs. 38.2%), mechanical ventilation (19.3% vs. 15.7%), and require vasopressors (21% vs. 13.8%). In-hospital mortality was 14.8% in E-CAP compared with 7.4% in P-CAP. The median cost of hospitalization was great in E-CAP than P-CAP ($12,420.1 vs. $9,857.5) Re-admission within 30 days was greater among patients with E-CAP than P-CAP (5.4% vs. 4%). 36.8% of isolates were resistant to fluoroquinolones, 10.4% to ceftriaxone and 18.1% to aminoglycosides. Only 10/1,247(0.8%) were multi-drug-resistant.Conclusion E. coli is an important cause of severe CAP, with higher mortality, greater need for ICU-level care, and higher re-admission rates than patients with pneumococcal pneumonia. The rate of fluoroquinolone resistance was high and empiric quinolones should be used with caution for patients who are critically ill due to E-CAPDisclosures A. Deshpande, 3M: Investigator, Research support; Clorox: Investigator and Speaker’s Bureau, Research grant and Speaker honorarium; Merck: Investigator and Speaker’s Bureau, Research support.

1115. Use of a Fluoroquinolone (FQ) vs. a Non-Fluoroquinolone (Non-FQ)-Based Antibiotic Regimen in the Treatment of Acute, Uncomplicated Diverticulitis

BackgroundThe management of acute, uncomplicated diverticulitis (DVT) remains based on expert consensus rather than on evidence from randomized clinical trials. The most common antibiotic (AB) regimen used in this patient population is metronidazole plus a fluoroquinolone (FQ). Non-FQ options, including B-lactam and non B-lactam regimens are available. Since there is a lack of clinical data comparing outcomes between these regimens, it remains uncertain whether patients presenting with acute, uncomplicated DVT require a FQ-based regimen. Increasing rates of FQ resistance and awareness of collateral damage have raised concern about whether this class should remain a first-line option.MethodsThis retrospective cohort study was conducted utilizing electronic health records to identify patients 18 years of age or older with acute, uncomplicated DVT, defined by ICD 10 codes. Patients included had CT confirmed DVT and were started on a guideline recommended AB regimen. Data points collected included length of stay, 30-day readmission due to DVT, time to conversion from IV to PO AB, progression to surgery, and discharge AB regimen. The primary objective is to evaluate differences in length of stay and 30 day re-admission rates. The secondary objectives are to evaluate time from intravenous (IV) to oral (PO) AB, progression to surgery, and discharge AB between the two groups.Results136 patients were evaluated, 71 FQ and 65 non-FQ. Length of stay was 4 days (1–18) in the FQ group vs. 5 days (1–19) in the non-FQ group (P = 0.236). 11% of patients in the FQ group vs. 9% of patients in the non-FQ group had a DVT related 30 day readmission (P = 0.451). 22% of patients in the FQ group vs. 23% of patients in the non-FQ group progressed to GI surgery during the admission. Time from IV to PO conversion of AB was 34.2 hours (0–63) in the FQ group vs. 48.4 hours (0–81) hours in the non-FQ group. Lastly, 63 of the 71 patients who were started on a FQ were discharged on an oral FQ vs. Forty patients of the 65 patients started on a non-FQ were discharged on an oral FQConclusionIn the treatment of acute, uncomplicated DVT outcomes including length of stay, 30-day readmission, time from IV to PO AB, and progression to surgery were comparable in patients receiving treatment with a FQ based AB regimen vs. a non-FQ based regimen.Disclosures D. Martin, GlaxoSmithKline: Independent Contractor, SalarySyneos Health: Employee, Salary.

Frequency of DNA gyrase and topoisomerase IV mutations and plasmid-mediated quinolone resistance genes among Escherichia coli and Klebsiella pneumoniae isolated from urinary tract infections in Azerbaijan, Iran.

This study assessed genetic alterations in gyrA, gyrB, parC and parE and the prevalence of plasmid-mediated quinolone resistance (PMQR) genes among Escherichia coli and Klebsiella pneumoniae isolates from urinary tract infections (UTIs) in Azerbaijan, Iran. A total of 205 clinical isolates of E. coli (n=177) and K. pneumoniae (n=28) were obtained from UTIs. Antimicrobial susceptibility was determined by disk diffusion and agar dilution assays. The presence of PMQR genes was determined by PCR, and sequencing of the gyrA, gyrB, parC and parE was performed. The rate of fluoroquinolone (FQ) resistance among the isolates was 77.1%. The Ser83Leu mutation in gyrA was observed in all 60 FQ-resistant isolates selected for direct sequencing. The second most common mutation in gyrA was Asp87Asn. Frequent mutations in parC were Ser80Ile and Glu84Val. Ser359Ala+Ser367Thr and Gly385Cys mutations in gyrB were identified in one isolate each of K. pneumoniae and E. coli, respectively. The parE gene had mutations at Ile529Leu, Ser458Ala and Leu416Phe. Overall, PMQR determinants were identified in 90% of E. coli and 100% of K. pneumoniae. The prevalence of PMQR genes was as follows: aac(6')-Ib-cr, 71.7%; oqxB, 51.7%; oqxA, 36.7%; qnrB, 28.3%; qnrS, 21.7%; qnrD, 16.7%; qepA, 5.0%; qnrA, 1.7%; and qnrC, 1.7%. FQ resistance rates were high. Mutations in DNA gyrase and topoisomerase IV and the prevalence of PMQR genes in E. coli and K. pneumoniae isolates were alarming. Moreover, the combination of these resistance mechanisms plays an important role in high-level FQ resistance.

Trends in antibiotic susceptibility of enteric fever isolates from South India, 2002–2013

BackgroundEnteric fever is endemic in India. Trends in antibiotic resistance in Salmonella enterica subspecies enterica serovars Typhi and Paratyphi A isolates over the past 12 years were studied. MethodsA retrospective analysis of consecutive blood culture isolates of Salmonella Typhi and Salmonella Paratyphi A was performed from 2002 to 2013. Antibiotic susceptibility testing was carried out for ampicillin, chloramphenicol, cotrimoxazole, nalidixic acid (NA), ciprofloxacin and ceftriaxone by disc diffusion. The minimum inhibitory concentration of ciprofloxacin and azithromycin was determined using E-test strips. Mantel-Haenszel extended chi-square test was used for analysis of trends across years. ResultsThree thousand two hundred ninety-six Salmonella spp. were isolated; of which, 1905 were identified as Salmonella Typhi (58%) and 1393 as Salmonella Paratyphi A (42%). Multidrug resistance (chloramphenicol, ampicillin and cotrimoxazole) was relatively stable throughout the study period. NA resistance increased from 18% in 2007 to 100% in 2013 among Salmonella Paratyphi A isolates and from 67% to 82% among Salmonella Typhi isolates. Complete susceptibility to ceftriaxone and azithromycin was observed in this study. ConclusionsKnowledge of the local patterns of resistance would help in appropriate therapy for enteric fever. With increasing rates of fluoroquinolone resistance in our hospital setting, it is probably prudent to revert back to the first-line agents for treatment and save azithromycin and third-generation cephalosporins for difficult and non-responsive cases.

Risk Factors for Community-Onset Pneumonia Caused by Levofloxacin-Nonsusceptible Streptococcus pneumoniae.

Fluoroquinolones are antibiotics commonly used in the treatment of infections caused by Streptococcus pneumoniae. However, rates of fluoroquinolone resistance are increasing with their frequent use. We designed this study to verify current fluoroquinolone resistance rates and risk factors for community-onset pneumococcal pneumonia. A retrospective case-control study was conducted in a tertiary referral hospital. The study population comprised patients admitted for pneumococcal pneumonia between January 2011 and May 2017. The case group included community-onset pneumonia caused by levofloxacin-nonsusceptible S. pneumoniae. The control group consisted of two patients with levofloxacin-susceptible S. pneumoniae who were admitted around the same time as each case. A total of 198 pneumococcal pneumonia cases were identified during the study period. Twenty-five levofloxacin-resistant S. pneumoniae cases and 3 levofloxacin-intermediate S. pneumoniae cases were included in the case group (nonsusceptibility rate = 14.1%). Multivariate analysis showed that healthcare-associated factors (odds ratio [OR] 4.78, 95% confidence interval [CI] 1.39-16.43, p = 0.013), bronchopulmonary disease (OR 3.79, 95% CI 1.07-13.40, p = 0.039), cerebrovascular disease (OR 6.08, 95% CI 1.24-29.75, p = 0.026), and exposure to fluoroquinolones within the previous 3 months (OR 5.89, 95% CI 1.21-28.68, p = 0.028) were associated with nonsusceptibility to levofloxacin. Independent risk factors for levofloxacin-nonsusceptible pneumococcal pneumonia were recent hospitalization, bronchopulmonary disease, cerebrovascular disease, and prior antibiotic use within 3 months. Careful selection of empirical antibiotics is thus needed in at-risk patients. Similarly, efforts to prevent the interpersonal spread of drug-resistant pathogens in long-term care facilities and to restrict unnecessary fluoroquinolone prescriptions are important.

Antimicrobial lubricant reduces rectal bacteria at transrectal prostate biopsy: results from a prospective randomized trial.

Antibiotic resistance may lead to increasing infection rates at transrectal prostate biopsy. Local antimicrobial agents might help to reduce bacterial load. The aim of this study was to test the potency of antimicrobial lubricants to reduce local bacterial loads and specifically fluoroquinolone-resistant strains. Overall, 384 prostate biopsy (PBx) patients of a larger prospective randomized trial (n=1000) were included. Patients were randomized for biopsy with pre-interventional instillation of an antimicrobial lubricant (intervention group n=256) or with the standard lubricant (control group n=128). Bacteria were recovered on pre- and post-biopsy rectal swab cultures from both patient groups. Bacterial colonization was semi-quantitatively recorded and analyzed for the presence of ciprofloxacin-resistant isolates. Within the intervention group, where antimicrobial lubricant was instilled for PBx, the post-biopsy bacterial count was statistically significantly lower compared to prior biopsy bacterial count (p<0.001), while in the control group, no statistically significant difference was shown. Moreover, our results demonstrated the tendency for reduction in ciprofloxacin-resistant bacteria growth when instillation of antimicrobial lubricant was used (9.4% versus 5.9%, p=0.5 prior- and post-biopsy). No reduction in ciprofloxacin-resistant bacterial growth was demonstrated for the control group. Ciprofloxacin-resistance was shown in overall 30 (7.8%) patients. Our data demonstrated that the antimicrobial lubricant prior biopsy leads to reduced bacterial load. Moreover, our data show the tendency for reduced ciprofloxacin-resistant bacteria growth when antimicrobial lubricant was instilled prior biopsy. However, the incidence of ciprofloxacin-resistant bacteria is low in our patient population. Rectal swabs should assess fluoroquinolone-resistance rates at prostate biopsy.

Plasmid-mediated quinolone resistance – PMQR MECHANIZMY OPORNOŚCI NA FLUOROCHINOLONY

Abstract Fluoroquinolones(FQ) are broad-spectrum antimicrobial agents widely used to treat a range of infections in clinical medicine. However, the surveillance studies demonstrate that fluoroquinolone resistance rates increased in Enterobacteriaceae in the past years. FQ inhibit bacterial DNA synthesis by interfering with the action of two bacterial enzymes - DNA gyrase and topoisomerase IV. There are two categories of quinolone resistance mechanisms: chromosomally encoded and acquired. Mutations in chromosomal genes encoding gyrase and topoisomerase IV are the most common mechanisms responsible for high-level fluoroquinolone resistance. Mutations can occur also in regulatory genes which control the expression of native efflux pumps located in bacterial membrane. Furthermore, three mechanisms of plasmid-mediated quinolone resistance (PMQR) have been discovered so far, including Qnr proteins, the aminoglycoside acetylotransferase variant - AAC(6’)-Ib-cr, and plasmid-mediated efflux pumps - QepA and OqxAB. Although the PMQR mechanisms alone cause only low-level resistance to fluoroquinolone, they can complement other mechanisms of chromosomal resistance and facilitate the selection of higher-level resistance. Moreover, plasmids with PMQR mechanisms often encode additional resistance traits (ESBLs, pAmpC, KPC) contributing to multidrug resistance (MDR). This review is focused on a range of molecular mechanisms which underlie quinolone resistance. 1. Introduction. 2. Mechanisms of fluoroquinolone action. 3. Chromosomally-encoded fluoroquinolone resistance. 3.1. Mutations changing the functions of target enzymes. 3.2. Reduction of drug concentration in the cytoplasm - efflux pump. 4. Plasmid-mediated quinolone resistance. 4.1. Qnr proteins. 4.2. AAC(6’)-Ib-cr enzyme. 4.3. Plasmid-mediated efflux pump: QepA i OqxAB. 4.4. The impact of PMQR on fluoroquinolone susceptibility level. 5. Summary

Levofloxacin for febrile neutropenia prophylaxis in acute myeloid leukemia patients associated with reduction in hospital admissions.

The purpose of this study is to evaluate the efficacy and safety of prophylactic oral levofloxacin in acute myeloid leukemia (AML) patients after receiving consolidation chemotherapy to prevent febrile neutropenia. We conducted a retrospective chart review of 50 AML patients who were prescribed levofloxacin and 50 AML patients who were not prescribed levofloxacin post-consolidation chemotherapy between June 2006 and August 2013 at a tertiary academic medical center. The primary outcome of this study was to evaluate the effectiveness of levofloxacin in preventing hospital readmission due to febrile neutropenia. Secondary outcomes evaluated the safety of this therapy, including the rate of Clostridium difficile-associated diarrhea (CDAD) within 30days from discharge of receiving consolidation chemotherapy and rate of fluoroquinolone resistance in positive bacterial cultures. Hospital readmission due to febrile neutropenia after the first consolidation cycle occurred in 42% of patients prescribed levofloxacin, as compared to 72% that were not prescribed levofloxacin (p = 0.002). This was also significantly reduced when levofloxacin was prescribed after all consolidation cycles (51.4 vs. 67%, p = 0.023). CDAD did not occur in any patient prescribed levofloxacin after the first cycle, compared to one case in those not prescribed levofloxacin. Evaluation of the impact on fluoroquinolone resistance was limited due to a paucity of fluoroquinolone susceptibilities reported. Prescribing oral levofloxacin post-consolidation chemotherapy in AML patients is associated with a reduction in febrile neutropenia. Further research is required to identify the impact on fluoroquinolone resistance and risk of CDAD.

Effect of an organic acids based feed additive and enrofloxacin on the prevalence of antibiotic-resistant E. coli in cecum of broilers

Increasing antibiotic resistance is a major public health concern. Fluoroquinolones are used to treat and prevent poultry diseases worldwide. Fluoroquinolone resistance rates are high in their countries of use. The aim of this study was to evaluate the effect of an acids-based feed additive, as well as fluoroquinolone antibiotics, on the prevalence of antibiotic-resistant E. coli. A total of 480 broiler chickens (Ross 308) were randomly assigned to 3 treatments: a control group receiving a basal diet; a group receiving a feed additive (FA) based on formic acid, acetic acid and propionic acid; and an antibiotic enrofloxacin (AB) group given the same diet, but supplemented with enrofloxacin in water. A pooled fecal sample of one-day-old chicks was collected upon arrival at the experimental farm. On d 17 and d 38 of the trial, cecal samples from each of the 8 pens were taken, and the count of E. coli and antibiotic-resistant E. coli was determined.The results of the present study show a high prevalence of antibiotic-resistant E. coli in one-day-old chicks. Supplementation of the diet with FA and treatment of broilers with AB did not have a significant influence on the total number of E. coli in the cecal content on d 17 and d 38 of the trial. Supplementation with FA contributed to better growth performance and to a significant decrease (P ≤ 0.05) in E. coli resistant to ampicillin and tetracycline compared to the control and AB groups, as well as to a decrease (P ≤ 0.05) in sulfamethoxazole and ciprofloxacin-resistant E. coli compared to the AB group. Treatment with AB increased (P ≤ 0.05) the average daily weight compared to the control group and increased (P ≤ 0.05) the number of E. coli resistant to ciprofloxacin, streptomycin, sulfamethoxazole and tetracycline; it also decreased (P ≤ 0.05) the number of E. coli resistant to cefotaxime and extended spectrum beta-lactamase- (ESBL-) producing E. coli in the ceca of broilers.

Fluoroquinolone prophylaxis in haematological cancer patients with neutropenia: ECIL critical appraisal of previous guidelines

Fluoroquinolone (FQ) prophylaxis was recommended in 2005 by European Conference on Infections in Leukemia (ECIL) for patients with prolonged neutropenia. In consideration of a worldwide increase in antibiotic resistance, the issue of FQ prophylaxis during neutropenia was re-evaluated. Literature review of randomised controlled trials (RCT) and observational studies published in years 2006-2014 was performed. Their results were analysed in meta-analysis. Meta-regression model was applied to evaluate whether the rates of FQ resistance in community and hospital settings influenced the efficacy of FQ prophylaxis. The impact of FQ prophylaxis on colonisation and infection with resistant bacteria was reviewed. Two RCTs and 12 observational studies were identified. FQ prophylaxis did not have effect on mortality (pooled OR 1.01, 95%CI 0.73-1.41), but was associated with lower rate of bloodstream infections (BSI) (pooled OR 0.57, 95%CI 0.43-0.74) and episodes of fever during neutropenia (pooled OR 0.32, 95%CI 0.20-0.50). No effect of the background rate of FQ resistance on the efficacy of FQ prophylaxis was observed. In few studies, FQ prophylaxis resulted in an increased colonisation or infection with FQ- or multi-drug resistant strains. The possible benefits of FQ prophylaxis on BSI rate, but not on overall mortality, should be weighed against its impact in terms of toxicity and changes in local ecology in single centres.

Prevalence and Mechanism of Fluoroquinolone Resistance in Escherichia coli Isolated from Swine Feces in Korea

In this study, we investigated the prevalence and fluoroquinolone (FQ) resistance mechanisms in Escherichia coli isolated from swine fecal samples. E. coli isolates were collected from 171 (72.2%) of 237 swine fecal samples. Of these, 59 isolates (34.5%) were confirmed as FQ-resistant E. coli by the disk diffusion method. Of the FQ-resistant isolates, three major FQ resistance mechanisms were investigated. Of the 59 isolates, plasmid-mediated quinolone resistance genes were detected in 9 isolates (15.3%). Efflux pump activity was found in 56 isolates (94.9%); however, this was not correlated with the increased FQ resistance measured by determining the MIC. Point mutations in quinolone resistance-determining regions were the main cause of FQ resistance. All 59 ciprofloxacin-resistant isolates had mutations in quinolone resistance-determining regions; of these 59 isolates, all (100%) had mutations in gyrA, 58 (98.3%) had mutations in parC, 22 (37.3%) had mutations in parE, and none had mutations in gyrB. The predominant mutation type was double mutation in gyrA (Ser83Leu plus mutation in aspartic acid 87), and all FQ-resistant isolates (except one) that had mutations in parC or parE also had double mutations in gyrA. Importantly, the frequencies of multidrug-resistant and extended-spectrum β-lactamase-producing E. coli were significantly higher in the high ciprofloxacin MIC group in this study. Compared with previous studies in Korea, the prevalence of FQ resistance and plasmid-mediated quinolone resistance genes had increased considerably in swine. Although the use of FQ as a feed additive is prohibited in Korea, use for self-treatment and therapeutic purposes has been increasing, which may be responsible for the higher FQ resistance rate observed in this study. Therefore, prudent use of FQ on animal farms is warranted to reduce the evolution of FQ-resistant bacteria in the animal industry.

Prevalence of macrolide and fluoroquinolone resistance-mediating mutations in Mycoplasma genitalium in five cities in Russia and Estonia.

Background and objectiveResistance in the sexually transmitted bacterium Mycoplasma genitalium to all recommended therapeutic antimicrobials have rapidly emerged. However, to date, internationally reported resistance surveillance data for M. genitalium strains circulating in Eastern Europe are entirely lacking. The aim of this study was to estimate the prevalence of macrolide and fluoroquinolone resistance-associated mutations in M. genitalium in four cities in Russia and one in Estonia, 2013–2016.Materials and methodsConsecutive urogenital samples found positive for M. genitalium during diagnostic testing were retrospectively analyzed for resistance-associated mutations in the 23S rRNA and parC genes using pyrosequencing and conventional Sanger sequencing, respectively.ResultsIn total, 867 M. genitalium positive samples from 2013–2016 were analyzed. Macrolide resistance-associated mutations were detected in 4.6% of the samples from Russia (0.7–6.8% in different cities) and in 10% of the samples from Estonia. The mutations A2059G and A2058G were highly predominating in both Russia and Estonia, accounting together for 90.9% of the cases positive for nucleotide substitutions in the 23S rRNA gene. The rates of possible fluoroquinolone resistance-associated mutations were 6.2% in Russia (2.5–7.6% in different cities) and 5% in Estonia. The mutations S83I and S83N were the most frequent ones in Russia (24.4% each), whereas D87N highly predominated in Estonia (83.3% of all fluoroquinolone resistance-associated mutations). Approximately 1% of the samples in both countries harbored both macrolide and possible fluoroquinolone resistance-associated mutations, with A2058G and S83I being the most frequent combination (37.5%).ConclusionsThe prevalence of macrolide and fluoroquinolone resistance-associated mutations in M. genitalium was 4.6% and 6.2%, respectively, in Russia, and 10% and 5%, respectively, in Estonia. Despite the relatively low rates of macrolide and fluoroquinolone resistance in these countries, antimicrobial resistance surveillance and testing for resistance-associated mutations in M. genitalium positive cases would be valuable.

Prospective Monitoring and Adapting Strategies for Prevention of Infection Following Transrectal Prostate Procedures

IntroductionA number of strategies have been attempted to minimize the risk of infection following transrectal prostate procedures. We report our prospective efforts at augmenting our prophylaxis strategy over time. MethodsSince 2010 we have prospectively monitored infections after transrectal prostate procedures and changed our prophylaxis regimen twice in an effort to respond to increases in infectious complications. In 2011 we added a single dose of intramuscular aminoglycoside to our prophylaxis regimen of fluoroquinolones or trimethoprim-sulfamethoxazole. In 2015 we began performing formalin needle tip disinfection before each biopsy and screening high risk patients for antibiotic resistance using rectal swab cultures (targeted prophylaxis). We report our rates of infections and antibiotic resistance patterns during this period. ResultsFrom 2010 to 2016 we performed 2,398 transrectal prostate procedures. Overall there were 41 cases (1.7%) of infection related hospitalization. However, the rate differed significantly during the course of the study period. The infection related hospitalization rate declined from 3.8% to 1.1% in the first 3 years following the addition of intramuscular aminoglycoside (2011 to 2013), a decrease of 69%. In 2014 our infection rate increased to 2.6%, prompting the initiation of protocol 3, wherein the addition of target prophylaxis and formalin needle tip disinfection identified a 29.8% fluoroquinolone resistance rate and resulted in another decline in our infection rate to 1.2% (a decrease of 53%). ConclusionsWhile the initial addition of intramuscular aminoglycoside appeared to be effective in decreasing post-procedure infections, further augmentation of our prophylaxis regimen through rectal swab screening of high risk patients and formalin needle tip disinfection led to an additional decline in rates of infection related hospitalizations.

Trends in rates of Gram-negative Bloodstream Infections (BSI) and Fluoroquinolone (FQ) resistance in Allogeneic Hematopoietic Cell Transplant (HCT) Recipients at Memorial Sloan Kettering Cancer Center (MSK) during 2012–2016

Trends in rates of Gram-negative Bloodstream Infections (BSI) and Fluoroquinolone (FQ) resistance in Allogeneic Hematopoietic Cell Transplant (HCT) Recipients at Memorial Sloan Kettering Cancer Center (MSK) during 2012–2016

Epidemic spread of multidrug-resistant tuberculosis in China

An estimated 10·4 million people worldwide developed tuberculosis in 2015. Tuberculosis is the leading infectious cause of death worldwide, with 1·8 million deaths, more than HIV/AIDS and malaria combined. 1 WHOGlobal tuberculosis report 2016. http://www.who.int/tb/publications/global_report/en/ Google Scholar In 2015, 580 000 (5·7%) patients with tuberculosis had rifampicin-resistant or multidrug-resistant (MDR; resistant to isoniazid and rifampicin) disease, with India and China having the greatest number of these cases. 1 WHOGlobal tuberculosis report 2016. http://www.who.int/tb/publications/global_report/en/ Google Scholar Improved living standards in China have led to global gains in tuberculosis control in the past 20 years, particularly in the western Pacific region. 2 Raviglione M Marais B Floyd K et al. Scaling up interventions to achieve global tuberculosis control: progress and new developments. Lancet. 2012; 379: 1902-1913 Summary Full Text Full Text PDF PubMed Scopus (264) Google Scholar However, a survey 3 Zhao Y Xu S Wang L et al. National survey of drug-resistant tuberculosis in China. N Engl J Med. 2012; 366: 2161-2170 Crossref PubMed Scopus (515) Google Scholar done in 2007 showed MDR tuberculosis in 6% of new cases and in 26% of cases with a tuberculosis treatment history. Rates of concurrent fluoroquinolone resistance in these patients were also high. 4 Zhang Z Lu J Wang Y Pang Y Zhao Y Prevalence and molecular characterization of fluoroquinolone-resistant Mycobacterium tuberculosis isolates in China. Antimicrobial Agents Chemother. 2014; 58: 364-369 Crossref PubMed Scopus (66) Google Scholar Initial assumptions were that most cases of MDR tuberculosis represented acquired drug resistance, 5 Marais BJ The global tuberculosis situation and the inexorable rise of drug-resistant disease. Adv Drug Deliv Rev. 2016; 102: 3-9 Crossref PubMed Scopus (28) Google Scholar but a 2015 analysis 6 Wei-wei Jiao W Liu Z Han R et al. Prevalence of drug resistant Mycobacterium tuberculosis among children in China. Tuberculosis. 2015; 95: 315-320 Summary Full Text Full Text PDF PubMed Scopus (18) Google Scholar of 100 children with culture-confirmed tuberculosis showed high rates of drug resistance suggesting active transmission of MDR tuberculosis within China. Transmission of multidrug-resistant Mycobacterium tuberculosis in Shanghai, China: a retrospective observational study using whole-genome sequencing and epidemiological investigationRecent transmission of MDR tuberculosis strains, with increasing drug-resistance, drives the MDR tuberculosis epidemic in Shanghai, China. Whole-genome sequencing can measure of the heterogeneity of drug-resistant mutations within and between hosts and help to determine the transmission patterns of MDR tuberculosis. Full-Text PDF

Increasing Rates of Fluoroquinolone Resistance in Escherichia coli Isolated From the Blood and Urine of Patients with Hematologic Malignancies and Stem Cell Transplant Recipients.

Fluoroquinolone (FQ) antibiotics have been shown to reduce mortality and the number of febrile episodes when used as prophylaxis during neutropenia. Prior studies suggest that prophylaxis may result in increasing rates of FQ resistance. Fluoroquinolone non-susceptibility trends in Escherichia coli isolated from blood and urine cultures were evaluated over a 16-year period during which prophylaxis was initiated in patients with hematologic malignancies and stem cell transplants. Non-susceptibility rates increased after the introduction of prophylaxis, with yearly non-susceptibility rates rising from 30%–33% to 40%–88% in blood isolates. The high rates of non-susceptibility now observed raise concerns about the continued efficacy of FQ prophylaxis. This concern exists particularly in those patients undergoing stem cell transplants where the total FQ non-susceptibility rates over the study period were 82.3%. Further evaluation of the effect of FQ prophylaxis on antibiotic resistance and its efficacy in the setting of increased rates of resistance is warranted.