Objectives: Since the introduction of the 13-lactam/13-lactamase inhibitor ceftazidime-avibactam (CZA), rapid evolution of resistance has been reported in different KPC-producing Klebsiella... Show moreObjectives: Since the introduction of the 13-lactam/13-lactamase inhibitor ceftazidime-avibactam (CZA), rapid evolution of resistance has been reported in different KPC-producing Klebsiella pneumoniae isolates. In this multicenter retrospective study, we describe the emergence of CZA resistance and evaluate the mutations that might be responsible for the restoration of carbapenem susceptibility. Methods: During a study period of 18 months, KPC-producing K. pneumoniae isolates of five hospitalized patients were collected with phenotypic development of CZA resistance. Results: In vitro restoration of carbapenem susceptibility during treatment was observed in 3 isolates. Whole genome sequencing of these isolates showed a D179Y mutation in the KPC gene of 2 variants and a KPC-2 with a A242-GT-243 deletion (KPC-14). Two KPC-3 variants showed CZA resistance with sustained carbapenemase activity without genomic adaptations in the KPC gene. Conclusions: This study confirms the emergence of CZA resistance in KPC K. pneumoniae. The role of carbapenems in treating patients with these variants is unclear and combination therapies warrant further investigation.(c) 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved. Show less
Lambregts, M.M.C.; Molendijk, E.B.D.; Meziyerh, S.; Schippers, E.F.; Delfos, N.M.; Leendertse, M.; ... ; Boer, M.G.J. de 2020
Objective A cornerstone in the management ofStaphylococcus aureusbacteraemia (SAB) is the differentiation between a complicated and an uncomplicated SAB course. The ability to early and accurately... Show moreObjective A cornerstone in the management ofStaphylococcus aureusbacteraemia (SAB) is the differentiation between a complicated and an uncomplicated SAB course. The ability to early and accurately identify patients with - and without - complicated bacteraemia may optimise the utility of diagnostics and prevent unnecessary prolonged antibiotic therapy. Methods Development and validation of a prediction score in SAB using demographic, clinical, and laboratory data from two independent Dutch cohorts; estimating the risk of complicated disease at the time of the first positive blood culture. Models were developed using logistic regression and evaluated by c-statistics, ie area under the ROC-curve, and negative predictive values (NPV). Results The development- and validation cohorts included 150 and 183 patients, respectively. The most optimal prediction model included: mean arterial pressure, signs of metastatic infection on physical examination, leucocyte count, urea level and time to positivity of blood cultures (c-statistic 0.82, 95% CI 0.74-0.89). In the validation cohort, the c-statistic of the prediction score was 0,77 (95% CI 0.69-0.84). The NPV for complicated disease for patients with a score of <= 2 was 0.83 (95% CI 0.68-0.92), with a negative likelihood ratio of 0.14 (95% CI 0.06-0.31). Conclusion The early SAB risk score helps to identify patients with high probability of uncomplicated SAB. However, the risk score's lacked absolute discriminative power to guide decisions on the management of all patients with SAB on its own. The heterogenicity of the disease and inconsistency in definitions of complicated SAB are important challenges in the development of clinical rules to guide the management of SAB. Show less
Bianco, G.; Boattini, M.; Asten, S.A.V. van; Iannaccone, M.; Zanotto, E.; Zaccaria, T.; ... ; Costa, C. 2020
We prospectively compared the performance of RESIST-5 O.O.K.N.V. and NG-Test Carba 5 assays directly from blood cultures spiked with 130 characterized Enterobacterales isolates. Overall, both... Show moreWe prospectively compared the performance of RESIST-5 O.O.K.N.V. and NG-Test Carba 5 assays directly from blood cultures spiked with 130 characterized Enterobacterales isolates. Overall, both assays yielded 100% sensitivity to detect KPC-type carbapenemases and OXA-48-like carbapenemases. Both assays failed to detect KPC-31 and KPC-33, D179Y point mutation variants of KPC-3 and KPC-2, that are deprived of carbapenemase activity and confer resistance to ceftazidime-avibactam. On blood culture bacterial pellets, NDMand VIM-type carbapenemases were detected in 50.0% and 52.2%, respectively, by RESIST5 O.O.K.N.V. vs 100% by NG-Test Carba 5. The sensitivity of RESIST-5 O.O.K.N.V. improved to 100% and 95.6%, respectively, by performing the assay on 4-h early subculture. (C) 2020 Published by Elsevier Ltd on behalf of The Healthcare Infection Society. Show less
Lambregts, M.M.C.; Wijnakker, R.; Bernards, A.T.; Visser, L.G.; Cessie, S. le; Boer, M.G.J. de 2020
Background: Timely empiric antimicrobial therapy is one of the cornerstones of the management of suspected bloodstream infection (BSI). However, studies about the effects of empiric therapy on... Show moreBackground: Timely empiric antimicrobial therapy is one of the cornerstones of the management of suspected bloodstream infection (BSI). However, studies about the effects of empiric therapy on mortality have reported inconsistent results. The objective of this study was to estimate the effect of delay of appropriate empiric therapy on early mortality in patients with BSI. Methods: Data for the propensity score matching (PSM) study were obtained from a cohort of patients with BSI. Inadequate empiric treatment was defined as in vitro resistance to the antimicrobial regimen administered < 6 h after blood cultures were taken. The primary outcome measure was 14-day mortality. Thirty-day mortality and median length of stay (LOS) were secondary outcomes. PSM was applied to control for confounding. Results: Of a total of 893 included patients with BSI, 35.7% received inadequate initial empiric treatment. In the PSM cohort (n = 334), 14-day mortality was 9.6% for inadequate antibiotic treatment, compared to. 10.2% in adequate empiric treatment (p = 0.85). No prolonged median LOS was observed in patients who initially received inadequate therapy (10.5 vs. 10.7 days, p = 0.89). Conclusions: In this study, we found no clear effect of inadequate empirical treatment on mortality in a low-risk BSI population. The importance of early empiric therapy compared to other determinants, may be limited. This may not apply for specific subpopulations, e.g., patients with sepsis. Show less
Introduction. The course of both the bacterial species and load and the incidence of infection during negative pressure wound therapy (NPWT) are unclear, with published studies presenting... Show moreIntroduction. The course of both the bacterial species and load and the incidence of infection during negative pressure wound therapy (NPWT) are unclear, with published studies presenting contradicting results. Objective. The aim of the study is to assess the changes in both bacterial species and load, as well as the incidence of infection, before and after NPWT in a patient population with a variety of wounds. Methods. Surgical patients 18 years of age or older who needed NPWT were included in this multicenter, prospective cohort study. A wound swab culture was taken before NPWT and either immediately following NPWT or 6 weeks of follow-up. The change of bacterial species, bacterial load, and rate of infection were determined before and after the start of NPWT. Results. In total, 104 patients were analyzed. The number of positive cultures increased from pre- to post-NPWT. The most cultured pathogenic bacterium was Staphylococcus aureus. The bacterial load was moderately higher at the end of NPWT than at the start (P < .0001). It was noted that 2 swabs contained multidrug-resistant bacteria, 1 pre-NPWT and 1 post-NPWT. Prior to NPWT, 26 patients had a wound infection, 5 of which had a persisting infection at the end of the study. Post-NPWT, 14 patients developed a wound infection. Conclusions. The number of S aureus strains and overall bacterial load increased during NPWT, and the incidence of infection remained the same. Further studies should be conducted to determine whether the increase in bacterial load influences other wound outcome parameters. Show less
Prehn, J. van; Triest, M.I. van; Altorf-van der Kuil, W.; Dijk, K. van; Stuart, J.W.T.C.; Weersink, A.J.L.; ... ; Dutch Natl AMR Surveillance Study 2019
IMPORTANCE\nSelective decontamination of the digestive tract (SDD) and selective oropharyngeal decontamination (SOD) are prophylactic antibiotic regimens used in intensive care units (ICUs) and... Show moreIMPORTANCE\nSelective decontamination of the digestive tract (SDD) and selective oropharyngeal decontamination (SOD) are prophylactic antibiotic regimens used in intensive care units (ICUs) and associated with improved patient outcome. Controversy exists regarding the relative effects of both measures on patient outcome and antibiotic resistance.\nOBJECTIVE\nTo compare the effects of SDD and SOD, applied as unit-wide interventions, on antibiotic resistance and patient outcome.\nDESIGN, SETTING, AND PARTICIPANTS\nPragmatic, cluster randomized crossover trial comparing 12 months of SOD with 12 months of SDD in 16 Dutch ICUs between August 1, 2009, and February 1, 2013. Patients with an expected length of ICU stay longer than 48 hours were eligible to receive the regimens, and 5881 and 6116 patients were included in the clinical outcome analysis for SOD and SDD, respectively.\nINTERVENTIONS\nIntensive care units were randomized to administer either SDD or SOD.\nMAIN OUTCOMES AND MEASURES\nUnit-wide prevalence of antibiotic-resistant gram-negative bacteria. Secondary outcomes were day-28 mortality, ICU-acquired bacteremia, and length of ICU stay.\nRESULTS\nIn point-prevalence surveys, prevalences of antibiotic-resistant gram-negative bacteria in perianal swabs were significantly lower during SDD compared with SOD; for aminoglycoside resistance, average prevalence was 5.6% (95% CI, 4.6%-6.7%) during SDD and 11.8% (95% CI, 10.3%-13.2%) during SOD (P < .001). During both interventions the prevalence of rectal carriage of aminoglycoside-resistant gram-negative bacteria increased 7% per month (95% CI, 1%-13%) during SDD (P = .02) and 4% per month (95% CI, 0%-8%) during SOD (P = .046; P = .40 for difference). Day 28-mortality was 25.4% and 24.1% during SOD and SDD, respectively (adjusted odds ratio, 0.96 [95% CI, 0.88-1.06]; P = .42), and there were no statistically significant differences in other outcome parameters or between surgical and nonsurgical patients. Intensive care unit-acquired bacteremia occurred in 5.9% and 4.6% of the patients during SOD and SDD, respectively (odds ratio, 0.77 [95% CI, 0.65-0.91]; P = .002; number needed to treat, 77).\nCONCLUSIONS AND RELEVANCE\nUnit-wide application of SDD and SOD was associated with low levels of antibiotic resistance and no differences in day-28 mortality. Compared with SOD, SDD was associated with lower rectal carriage of antibiotic-resistant gram-negative bacteria and ICU-acquired bacteremia but a more pronounced gradual increase in aminoglycoside-resistant gram-negative bacteria.\nTRIAL REGISTRATION\ntrialregister.nlIdentifier: NTR1780. Show less
