Pediatric Febrile Urinary Tract Infection Caused by ESBL Producing Enterobacteriaceae Species.

BACKGROUND: Over the past decade, drug resistance pattern has worsened for many of the uropathogens due to overuse of antibiotics for empiric treatment. The burden of extended spectrum beta-lactamase (ESBL) producing Enterobacteriaceae associated urinary tract infections (UTI) has become increasingly more common, limiting treatment options among children presenting with febrile UTI. We investigated the burden and correlates of ESBL producing Enterobacteriaceae associated UTI among children and antibacterial resistance pattern. METHODS: 284 midstream urine specimens were collected using standard aseptic techniques from 284 children who were diagnosed with suspected UTI. Urine culture and bacteria isolation were performed following standard bacteriological techniques. The Kirby-Bauer disk diffusion technique and the double-disc synergy test were used to investigate antibiotic susceptibility and presence of ESBL production. RESULTS: UTI was confirmed using a positive urine culture for a relevant pathogen in 96/284 (33.8%) of the cases. Enterobacteriaceae accounted for 75% (72/96) of etiologies of UTI in children. The most frequent Enterobacteriaceae spp. were E. coli, 44.4% (32/72) and K. pneumonia, 27.8% (20/72). The overall multidrug resistance rate was 86.1% (62/72). ESBL-producers accounted for 41.7% (30/72) of the isolated Enterobacteriaceae. ESBL producing K. pneumonia and E. coli isolates accounted for 70% (14/20) and 37.5% (12/32), respectively. History of UTI in the past 1 year (adjusted odds ratio (AoR) = 0.08, 95%CI (0.01 - 0.57)) and medium family wealth index (AoR = 0.03, 95%CI (0.00 - 0.27)) protected from infection with ESBL-producing Enterobacteriaceae. Conclusion. ESBL production was more common in K. pneumonia and appeared to be a major factor contributing drug resistance UTI in children. The findings call for the need to incorporate ESBL testing in the routine clinical practice. The resistance level to commonly prescribed first-line antibiotics observed within Enterobacteriaceae was alarming calling for strengthened antimicrobial stewardship.

Evaluation of the in vitro activity of WCK 5222 (cefepime/zidebactam) and currently available combination therapies against single- and double-carbapenemase producing Enterobacteriaceae: Expanding the zone of hope.

Cefepime/zidebactam (WCK 5222) is a ß-lactam/ß-lactam enhancer antibiotic designed to retain in vitro activity against Enterobacteriaceae that simultaneously produce metallo-ß-lactamase (MBL) and serine-ß-lactamase (SBL). Aztreonam (ATM) plus ceftazidime/avibactam (CZA) or meropenem/vaborbactam (M/V) is an attractive option for coverage of such strains, but clinical laboratories are not equipped to distinguish which is the more potent regimen to inform treatment decisions. We evaluated Enterobacteriaceae that expressed MBL and ≥1 SBL (n=15) using gradient diffusion strip (GDS) methods to (1) determine the minimum inhibitory concentration (MIC) of WCK 5222 and (2) compare the in vitro potency of CZA+ATM vs. M/V+ATM. All isolates were non-susceptible to ATM, CZA, and M/V and were inhibited by WCK 5222 at cefepime concentrations ≥2 log2 dilutions below the susceptible-dose dependent breakpoint of 8 mg/L (MIC50/90, 1/2 mg/L). Activity of CZA+ATM vs. M/V+ATM was compared using the zone of hope (ZOH) product, quantitated by multiplying the length (in mm) of inhibited growth adjacent to each GDS from the point of intersection. The median (interquartile range) ZOH product for CZA+ATM and M/V+ATM was 75.4 (62.8-93.7) and 23.5 (14.1-60.4), respectively (P=0.002). In strains with one carbapenemase (the MBL), the median ZOH products were not statistically different, but in strains with an OXA-type carbapenemase (n=6), the median product for CZA+ATM and M/V+ATM was 78.1 and 20.7, respectively (P=0.004). Thus, CZA+ATM may offer enhanced coverage over M/V+ATM of Enterobacteriaceae co-expressing MBL and SBL. Further preclinical in vivo evaluations of WCK 5222 monotherapy are warranted.

Prognosis of urinary tract infection caused by KPC-producing Klebsiella pneumoniae: The impact of inappropriate empirical treatment.

INTRODUCTION: There is scarce information on the prognosis of urinary tract infections (UTI) caused by KPC carbapenemase-producing Klebsiella pneumoniae (KPC-Kp). OBJETIVE: To investigate the association between KPC-Kp aetiology and clinical failure and all cause mortality and to explore the impact of inappropriate empirical treatment. MATERIAL AND METHODS: This is a retrospective observational study of hospitalized patients with UTI due to K. pneumoniae. We explored clinical failure at day 21 and 30-day all-cause mortality using different models of adjusted analysis. RESULTS: We analyzed 142 episodes of UTI; 46 episodes (32.4%) were due to KPC-Kp and 96 episodes (67.6%) were due to non-KPC-Kp strains (62 wild type and 34 EBSL producer). Clinical failure was more frequent in the KPC-Kp group (41.3% vs. 15.6%, p = 0.001). KPC-Kp aetiology and inappropriate empirical therapy were associated in the non-adjusted analysis with clinical failure. When analysed in separate adjusted models, both were found to be associated; inappropriate empirical treatment (OR 2.51; 95% CI, 1.03-6.12; p = 0.04) and KPC-Kp (OR 2.73; 95% CI, 1.03-7.22; p = 0.04) were associated with increased risk of failure. All-cause 30-day mortality was higher in patients with KPC-Kp UTI (39.1% vs. 15.6%, p = 0.002). Bacteraemia was more frequent in patients with KPC-Kp etiology (23.9% vs. 10.4%; p = 0.034). In both cases, the association was not confirmed in the adjusted analysis. CONCLUSION: KPC-Kp UTI is associated with higher clinical failure and may be due to an increase in inappropriate empirical treatment.

Antimicrobial susceptibility and impact of macrolide antibiotics on Moraxella catarrhalis in the upper and lower airways of children with chronic endobronchial suppuration.

INTRODUCTION: Moraxella catarrhalis is an important but insufficiently studied respiratory pathogen. AIM: To determine antibiotic susceptibility and impact of recent antibiotics on M. catarrhalis from children with chronic endobronchial suppuration. METHODOLOGY: We cultured nasopharyngeal (NP) swabs and bronchoalveolar lavage (BAL) fluids collected from children who were prospectively enrolled in studies of chronic cough and had flexible bronchoscopy performed. Recent ß-lactam or macrolide antibiotic use was recorded. M. catarrhalis isolates stored at -80 °C were re-cultured and susceptibility determined to a range of antibiotics including the macrolide antibiotic erythromycin. RESULTS: Data from concurrently collected NP and BAL specimens were available from 547 children (median age 2.4 years) enrolled from 2007 to 2016. M. catarrhalis NP carriage was detected in 149 (27  %) children and lower airway infection (≥104 c.f.u. ml-1 BAL) in 67 (12  %) children. In total, 91  % of 222 M. catarrhalis isolates were ß-lactamase producers, and non-susceptibility was high to benzylpenicillin (98 %), cefaclor (39 %) and cotrimoxazole (38 %). Overall, >97  % isolates were susceptible to cefuroxime, chloramphenicol, erythromycin and tetracycline; three isolates were erythromycin-resistant (MIC >0.5 mg l-1). Recent macrolide antibiotics (n=152 children, 28 %) were associated with significantly reduced M. catarrhalis carriage and lower airway infection episodes compared to children who did not receive macrolides; odds ratios 0.19 (95  % CI 0.10-0.35) and 0.15 (0.04-0.41), respectively. CONCLUSION: Despite the frequent use of macrolides, few macrolide-resistant isolates were detected. This suggests a fitness cost associated with macrolide resistance in M. catarrhalis. Macrolide antibiotics remain an effective choice for treating M. catarrhalis lower airway infection in children with chronic endobronchial suppuration.

Inappropriate empirical antibiotic therapy does not adversely affect the clinical outcomes of patients with acute pyelonephritis caused by extended-spectrum ß-lactamase-producing Enterobacteriales.

Extended-spectrum ß-lactamase-producing Enterobacteriales (ESBL-PE) are often associated with inappropriate empirical therapy (IAT). The aim of this study was to investigate whether IAT of acute pyelonephritis (APN) caused by ESBL-PE is related to adverse outcomes. A retrospective cohort study was performed at a tertiary-care hospital from 2014 through 2016. Patients who had APN caused by ESBL-PE and were definitely treated with appropriate antibiotics for at least 7 days were enrolled. IAT was defined as when inappropriate empirical antibiotics were given 48 h or longer after initial diagnosis of APN. Primary endpoint was treatment failure defined as clinical and/or microbiologic failure. Secondary endpoints were length of hospital stay and recurrence of APN. Propensity score matching was used to adjust heterogeneity of each group. Among 175 eligible cases, 59 patients received IAT and 116 patients received appropriate empirical antimicrobial therapy (AT). Treatment failure was observed in five (8.4%) patients and nine (7.8%) patients in each group, respectively. After matching, the treatment failure rate was similar between both groups (adjusted odd ratio [aOR] 1.05; 95% confidence index [CI] 0.26-4.15). The length of hospital stay (median 11 days in the IAT group versus 11 days in the AT group; P = 0.717) and absence of recurrence within 2 months (90.3% in IAT and 86.7% in AT; P = 0.642) were also similar. IAT did not adversely affect the clinical outcome. In this regard, clinicians should be more cautious about indiscriminate prescription of broad-spectrum antibiotics such as carbapenem empirically for treatment of APN possibly caused by ESBL-PE.

Tigecycline resistance caused by rpsJ evolution in a 59-year-old male patient infected with KPC-producing Klebsiella pneumoniae during tigecycline treatment.

Carbapenem resistant Klebsiella pneumoniae (CRKP) nosocomial infection increased rapidly in recent years. By far, the anti-infection drugs for CRKP infection are limited. Tigecycline is one of the last resort treatments for CRKP infections. In this study, curative effect of tigecycline therapy was monitored in a 59-year-old male patient infected with KPC-producing K. pneumoniae. Consecutive clonal consistent K. pneumoniae isolates were cultured during tigecycline treatment. Whole genome sequencing of the isolates was performed, and bioinformatics analysis was further performed. Five isolates, four of which were susceptible and one resistant were collected. All of the isolates belong to Sequence Type 11 (ST11), and harbouring 11 gene sequences relevant to antibiotic resistance including blaKPC-2. One amino acid substitution V57L in rpsJ was identified in the tigecycline resistant isolates. Subsequent transformation experiment confirmed the contribution of the rpsJ variant (V57L) to reduced tigecycline susceptibility. To our knowledge, this study is the first report to provide direct in vivo evidence that evolution in the rpsJ gene can lead to tigecycline resistance in patients infected with KPC-producing K. pneumoniae during tigecycline treatment. This finding serves as a therapeutic warning as the rpsJ gene is on the chromosome of CRKP strains. Under selective pressure from tigecycline, the rpsJ mutation may occur and lead to tigecycline resistant.

Impact of cephalosporin restriction on incidence of infections with extended-spectrum beta-lactamase-producing Klebsiella pneumoniae in an endemic setting.

Decreasing cephalosporin use was described as an effective intervention in decreasing the incidence of infections caused by Klebsiella pneumoniae harbouring extended-spectrum beta-lactamase (ESBLKP). Due to sustained increased levels of infections caused by ESBLKP, a multifaceted antibiotic stewardship intervention aimed to decrease cephalosporin use was carried out at a large medical unit of a teaching hospital. All cephalosporins except the first-generation were restricted and could only be prescribed after authorization by an infectious disease physician. The use of cephalosporins decreased significantly after intervention. The effect was most prominent for the third-generation cephalosporins (7.9-1.5 DDD/100 OBD). There was an increase in the consumption of piperacillin/tazobactam, carbapenems and fluoroquinolones. In contrast to our expectations the ESBLKP incidence increased, but the changes were not statistically significant. The intervention was successful in controlling the prescribing of cephalosporins, but had no impact on incidence of ESBLKP infections.

Use of Monte Carlo simulation to evaluate the efficacy of tigecycline and minocycline for the treatment of pneumonia due to carbapenemase-producing Klebsiella pneumoniae.

BACKGROUND: Pneumonia caused by carbapenemase-producing Klebsiella pneumoniae (CP-KP) are increasingly encountered in hospitals worldwide, causing high mortality due to lack of treatment options. The goal of this study was to assess the efficacy of tigecycline and minocycline for CP-KP hospital-acquired pneumonia (HAP) by using Monte Carlo simulation. METHODS: A total of 164 non-duplicated CP-KP strains were collected from sputum or blood in patients with HAP. The MICs for antimicrobials were determined by the agar dilution method. A 10,000-patient Monte Carlo Simulation based on a PK/PD model incorporating the MICs and population pharmacokinetic parameters were conducted to calculate probability of target attainment (PTA) at each MIC value and total cumulative fraction of response (CFR). RESULTS: The susceptibility rate of tigecycline and minocycline were 79.9% and 41.5%, respectively. At recommended doses, an optimal PTA of 90% was obtained for treating HAP caused by CP-KP with MICs of tigecycline ≤0.5 mg/L or minocycline ≤4 mg/L. The CFR of tigecycline at the recommended dose and double dose (100 mg q12h) were 71.2% and 90.2%, respectively. The CFR of minocycline at recommended dose and double dose (200 mg q12h) was 53.4% and 77.2%, respectively. CONCLUSIONS: The findings of this study suggest that the recommended dose of tigecycline was not effective in HAP caused by CP-KP, and a higher CFR indicating a better clinical efficacy can be gained by doubling the dose (100 mg q12h). minocycline (200 mg q12h) might be a potential alternative of tigecycline to against strains with MICs ≤ 8 mg/L.

Cefepime versus carbapenems for the treatment of urinary tract infections caused by extended-spectrum ß-lactamase-producing enterobacteriaceae.

The aim of this study was to evaluate the effectiveness of cefepime compared with carbapenems for the management of urinary tract infections (UTIs) caused by extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae. This was a single-centre, retrospective study among patients with a documented ESBL-producing Enterobacteriaceae UTI between 1 July 2014 and 31 January 2017. Adult patients who received either cefepime or a carbapenem for symptomatic UTI were included in the analysis. The primary endpoint was clinical failure, defined by persistence of initial UTI symptoms that required escalation of therapy. Secondary endpoints included microbiological failure and relapse within 30 days. Of a total of 106 patients included in the study, 17 received cefepime and 89 received a carbapenem. None of the patients in either group experienced clinical or microbiological failure. Relapse occurred in six patients in the carbapenem group and none in the cefepime group. In conclusion, cefepime was comparable with carbapenems in the treatment of UTIs caused by ESBL-producing Enterobacteriaceae. Its use as a carbapenem-sparing agent for this indication should be further explored.

ESBL E coli and P. aeruginosa Resistance to Ceftolozane-Tazobactam in a Patient with a Liver Abscess. The Search for an Omnipotent Antibiotic Goes On!

Multi drug resistant (MDR) Pseudomonas aeruginosa and Extended- Spectrum-lactamase (ESBL) Enterobacteriaceae are becoming an increasing difficult clinical problem. Immediate resistance to some of the new antimicrobials such as ceftolozane/tazobactam is unusual and is due to a variety of mechanisms such as hyper-production of inactivating enzymes and gene mutation. In addition, previous antimicrobial administration is a well-recognized risk factor to develop resistance. We present a patient with a liver abscess where the organism was resistant to ceftolozane/tazobactam resulting in a poor clinical outcome.

"Double carbapenem" and oral fosfomycin for the treatment of complicated urinary tract infections caused by blaNDM -harboring Enterobacteriaceae in kidney transplantation.

Infections with carbapenemase-producing carbapenem-resistant Enterobacteriaceae represent an emergent problem worldwide. Treatment of infections caused by New Delhi metallo-beta-lactamase (NDM)-harboring Enterobacteriaceae is particularly challenging as it frequently involves the use of nephrotoxic agents, which is problematic in kidney transplant recipients and non-renal transplant patients with marginal kidney function. We present two cases of urinary tract infections caused by NDM-harboring Enterobacteriaceae successfully treated with a combination of "double carbapenem" and oral fosfomycin.

Extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae from urinary tract infections: Evolution of antimicrobial resistance and treatment options. / Escherichia coli y Klebsiella pneumoniae productores de betalactamasa de espectro extendido en infecciones de vías urinarias: evolución de la resistencia antibiótica y opciones terapéuticas.

BACKGROUND AND OBJECTIVES: A study of the susceptibility to antimicrobials of the extended spectrum beta-lactamase phenotypes (ESBL) in Escherichia coli and Klebsiella spp. was performed to discover the evolution of this type of resistance from urinary tract infections. MATERIAL AND METHOD: A retrospective study was carried out between 2012 and 2016. Susceptibility to ciprofloxacin, tobramycin, cefoxitin, fosfomycin, nitrofurantoin, co-trimoxazole, and carbapenems was analyzed using MicroScan® system. RESULTS: A total of 95,399 samples were processed and 9,772 E. coli, 1,784 Klebsiella pneumoniae and 248 Klebsiella oxytoca were isolated. ESBL strains were more frequent in women, although they decreased during 2015 and 2016 (65.7-67.2%). The prevalence of K. pneumoniae ESBL increased annually (28.1% in 2016). The average prevalence of E. coli ESBL was 10.5% with few oscillations. Higher resistance occurred to ciprofloxacin and cotrimoxazole, 89.5 and 94.7% in 2015, respectively, and there was lesser resistance to imipenem. Fosfomycin and nitrofurantoin were very active on E. coli ESBL. CONCLUSIONS: ESBL producing E. coli and K. pneumoniae were prevalent, especially the latter, with a significant resistance to ciprofloxacin and cotrimoxazole. Susceptibility to imipenem was high.

Current and future therapies for Pseudomonas aeruginosa infection in patients with cystic fibrosis.

Pseudomonas aeruginosa opportunistically infects the airways of patients with cystic fibrosis and causes significant morbidity and mortality. Initial infection can often be eradicated though requires prompt detection and adequate treatment. Intermittent and then chronic infection occurs in the majority of patients. Better detection of P. aeruginosa infection using biomarkers may enable more successful eradication before chronic infection is established. In chronic infection P. aeruginosa adapts to avoid immune clearance and resist antibiotics via efflux pumps, ß-lactamase expression, reduced porins and switching to a biofilm lifestyle. The optimal treatment strategies for P. aeruginosa infection are still being established, and new antibiotic formulations such as liposomal amikacin, fosfomycin in combination with tobramycin and inhaled levofloxacin are being explored. Novel agents such as the alginate oligosaccharide OligoG, cysteamine, bacteriophage, nitric oxide, garlic oil and gallium may be useful as anti-pseudomonal strategies, and immunotherapy to prevent infection may have a role in the future. New treatments that target the primary defect in cystic fibrosis, recently licensed for use, have been associated with a fall in P. aeruginosa infection prevalence. Understanding the mechanisms for this could add further strategies for treating P. aeruginosa in future.

Resistance to Ceftazidime-Avibactam Is Due to Transposition of KPC in a Porin-Deficient Strain of Klebsiella pneumoniae with Increased Efflux Activity.

Ceftazidime-avibactam is an antibiotic with activity against serine beta-lactamases, including Klebsiella pneumoniae carbapenemase (KPC). Recently, reports have emerged of KPC-producing isolates resistant to this antibiotic, including a report of a wild-type KPC-3 producing sequence type 258 Klebsiella pneumoniae that was resistant to ceftazidime-avibactam. We describe a detailed analysis of this isolate, in the context of two other closely related KPC-3 producing isolates, recovered from the same patient. Both isolates encoded a nonfunctional OmpK35, whereas we demonstrate that a novel T333N mutation in OmpK36, present in the ceftazidime-avibactam resistant isolate, reduced the activity of this porin and impacted ceftazidime-avibactam susceptibility. In addition, we demonstrate that the increased expression of blaKPC-3 and blaSHV-12 observed in the ceftazidime-avibactam-resistant isolate was due to transposition of the Tn4401 transposon harboring blaKPC-3 into a second plasmid, pIncX3, which also harbored blaSHV-12, ultimately resulting in a higher copy number of blaKPC-3 in the resistant isolate. pIncX3 plasmid from the ceftazidime-avibactam resistant isolate, conjugated into a OmpK35/36-deficient K. pneumoniae background that harbored a mutation to the ramR regulator of the acrAB efflux operon recreated the ceftazidime-avibactam-resistant MIC of 32 µg/ml, confirming that this constellation of mutations is responsible for the resistance phenotype.

IMP-6 Carbapenemase-Producing Enterobacteriaceae Bacteremia Successfully Treated with Amikacin-Meropenem in Two Patients.

Infections caused by carbapenemase-producing Enterobacteriaceae (CPE) are becoming increasingly common worldwide. Although CPE infections can be fatal, few reports in the literature have described effective and successful treatments for infectious diseases caused by several types of IMP CPE, and, to our knowledge, no reports have described the successful treatment of IMP-6 CPE infections. We describe two patients who developed bacteremia caused by IMP-6 CPE after surgery for cancer who were successfully treated with amikacin plus high-dose prolonged-infusion meropenem. Both patients were treated over a 2-week period using amikacin 15 mg/kg at various intervals based on therapeutic drug monitoring and meropenem 2000 mg infused over 3 hours every 12 hours. The dosages of amikacin and meropenem were determined based on the creatinine clearance of each patient. Both patients were cured of their bacteremia and did not experience any antibiotic-related adverse effects. Based on the outcomes of these patients, it appears that amikacin plus high-dose prolonged-infusion meropenem may be safe and effective for the treatment of bacteremia caused by IMP-6 CPE.

Thymol and carvacrol strongly inhibit biofilm formation and growth of carbapenemase-producing Gram negative bacilli.

Discovery of novel drugs with new mechanisms of action and without cross-reaction with current therapeutic agents is crucial in the management of infections caused by multi-drug resistant (MDR) bacteria. The aim of the present study was to investigate effects of carvacrol and thymol on biofilm formation and antimicrobial activity against different carbapenemase-producing Gram negative bacilli. The antimicrobial and antibiofilm effect of thymol and carvacrol was investigated against strains harboring different genes related to carbapenemase resistance. Antimicrobial resistance was examined by an agar dilution method and antibiofilm effect was evaluated by microtiter plate assay and staining by crystal violet. Thymol and carvacrol had antibacterial effects ranging from 200-1600 µg/mL and 62-250 µg/mL respectively, and antibiofilm effect from 125-500 and 400-1600 µg/mL respectively. Seoul imipenemase- (SIM) producing isolates had the highest sensitivity, and NDM (New Delhi metallo-beta-lactamase) producing isolates had the lowest sensitivity to these components. Findings of the present study indicated a potential role of carvacrol and thymol in controlling carbapenemase-producing gram negative bacterial infections. These findings helped to develop herbal drugs for replacing antibiotics. In addition, their antibiofilm effects showed that carvacrol and thymol inhibit biofilm formation of carbapenemase-producing strains.

Carbapenem-Resistant Enterobacteriaceae.

Carbapenem-resistant Enterobacteriaceae (CRE) have emerged as a major threat. Commonly used antibiotics are generally inactive against CRE. Therefore, timely detection of CRE is of paramount importance. Among CRE, those producing carbapenem-hydrolyzing ß-lactamase enzymes (carbapenemase-producing Enterobacteriaceae) are particularly of concern because they tend to spread, and treatment is difficult. The carbapenemase groups most commonly encountered include KPC, NDM, and OXA-48. Treatment options are limited and include combinations of polymyxins, tigecycline, aminoglycosides, or carbapenems; newer agents with activity against CRE and better safety profiles are becoming available and will likely emerge as the preferred therapy.

Clinical efficacy of ceftazidime/avibactam versus other active agents for the treatment of bacteremia due to carbapenemase-producing Enterobacteriaceae in hematologic patients.

OBJECTIVES: The primary objective was to describe clinical features, treatment and outcomes in patients with carbapenemase-producing Enterobacteriaceae (CPE) bacteremia. Additionally, patients treated with ceftazidime/avibactam (study group) were compared to the rest of the patients (comparator group) to determine the influence of the treatment in both crude mortality and clinical cure. METHODS: Multicenter and retrospective study that included patients with hematologic malignancies who had CPE bacteremia. A bivariate analysis was performed to compare the clinical variables between the study group and the control group. RESULTS: 31 patients were included. Bacteremia was considered primary in 14 (45%) patients. Overall crude mortality at 30days was 45.2% (n=14). Mortality was more frequent when septic shock (78.6% vs 11.8%; p>0.001) and higher Pitt score (6+14 vs 1.5+4; p<0.01) were present. 8 patients (25.8%) received treatment with ceftazidime/avibactam. No significant differences in crude mortality were found between study and comparator groups (p=0.19). In contrast, patients in study group had higher clinical cure rates than the comparator group within 14days of initiating treatment (85.7% vs. 34.8%, respectively, p=0.031). CONCLUSIONS: CPE bacteremia is associated with high mortality in patients with hematologic malignancies. Ceftazidime/avibactam may be an effective alternative for treating these patients.

Molecular Epidemiology of Colistin-Resistant, Carbapenemase-Producing Klebsiella pneumoniae in Serbia from 2013 to 2016.

Twenty-seven colistin-resistant, carbapenemase-producing Klebsiella pneumoniae isolates were identified from hospitals in Serbia. All isolates were blaCTX-M-15 positive; ST101, ST888, ST437, ST336, and ST307 were blaOXA-48 positive; and ST340 was blaNDM-1 positive. ST307 had an insertion, and ST336 had a premature stop codon in the mgrB gene. Amino acid substitutions were detected in PmrAB of isolates ST101, ST888, ST336, and ST307. The mcr-1 and mcr-2 were not detected. An increase in phoP, phoQ, and pmrK gene transcription was detected for all sequence types.

ESBL/AmpC-producing Enterobacteriaceae in households with children of preschool age: prevalence, risk factors and co-carriage.

OBJECTIVES: ESBL/AmpC-producing Enterobacteriaceae are an emerging public health concern. As households with preschool children may substantially contribute to the community burden of antimicrobial resistance, we determined the prevalence, risk factors and co-carriage of ESBL/AmpC-producing bacteria in preschool children and their parents. METHODS: From April 2013 to January 2015, each month 2000 preschool children were randomly selected from Dutch population registries. The parents were invited to complete an epidemiological questionnaire and to obtain and send a faecal sample from the selected child and from one parent. Samples were tested for ESBL/AmpC-producing bacteria. Logistic regression was used to identify risk factors for ESBL/AmpC carriage in children and parents, and findings were internally validated by bootstrapping. RESULTS: In total, 1016 families were included and ESBL/AmpC prevalence was 4.0% (95% CI 3.2%-5.0%); 3.5% (95% CI 2.5%-4.8%) in children and 4.5% (95% CI 3.4%-6.0%) in parents. Attending a daycare centre (DCC) was the only significant risk factor for children (OR 2.1, 95% CI 1.0-4.3). For parents, the only significant risk factor was having one or more children attending DCCs (OR 2.2, 95% CI 1.2-4.8). For parents of ESBL/AmpC-positive children the OR for ESBL/AmpC carriage was 19.7 (95% CI 9.2-42.4). Co-carriage of specific ESBL/AmpC genotypes in child and parent occurred more often than expected by chance (14.6% versus 1.1%, P < 0.001). CONCLUSIONS: In this study, intestinal carriage with ESBL/AmpCs was detected in ∼4% of households with preschool children. DCC attendance was a risk factor in both children and parents and co-carriage of specific genotypes frequently occurred in child-parent pairs. These findings suggest household transmission or/and family-specific exposure to common sources of ESBL/AmpC-producing bacteria.