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Objective. To evaluate frequency of pharyngeal and rectal mucosa colonization by K. pneumoniae strains in infants with congenital heart defects at the stage of cardiosurgical hospital admission, as well as dynamic analysis of production frequency and molecular structure of K. pneumoniae carbapenemases. Materials and Methods. A total of 1445 patients with risk factors (antibiotic therapy in the anamnesis, emergency hospitalization, transfer from other hospitals) admitted for surgical treatment of congenital heart defects (CHDs) between January 1, 2020 and December 31, 2022 were included in the retrospective analysis. Median age was 1.08 months (between 0 and 12 months). Smears from the pharyngeal and rectal mucosa (2890 samples) were taken for microbiological examination no later than 72 h after admission. The isolation of extended-spectrum beta-lactamases (ESBLs) and/or carbapenemases producing K. pneumoniae in the absence of symptomatic infection was considered as colonization. K. pneumoniae strains were considered as "problematic" in the absence of susceptibility to three or more groups of antimicrobials: the third- and fourth-generation cephalosporins, carbapenems, fluoroquinolones, aminoglycosides. The profile of antibiotic resistance, carbapenemases production and their molecular type were determined in the isolated strains. Results. K. pneumoniae carriage with "problematic" sensitivity was detected in 252 out of 1445 (17.4%) patients: 153 out of 1445 (10.6%) children were colonized by only ESBLs producers, and 99 out of 1445 (6.9%) children – by both ESBLs and carbapenemases producers. In dynamics, the number of ESBLs producers carriers decreased by 1.5 times (50 out of 448 – 11.2% and 37 out of 506 – 7.3% in 2020 and 2022, respectively). The number of K. pneumoniae producing both ESBLs and carbapenemases carriers increased by 4.9 times (11 out of 448 – 2.5% and 62 out og\f 506 – 12.3% in 2020 and 2022, respectively), in 2022 exceeding the proportion of only ESBLs producers carriers by 1.7 times. The molecular structure of carbapenemases was represented by OXA-48 carbapenemases (44 out of 99 – 44.5%), NDM metalloenzymes (35 out of 99 – 35.4%), OXA-48 and NDM combinations (13 out of 99 – 13.1%), KPC (3 out of 99 – 3%), NDM, KPC and OXA-48, NDM and KPC combinations: 3 out of 99 – 3% and 1 out of 99 – 1% of carriers, respectively. In dynamics, the number of isolates with the production of OXA-48 carbapenemases increased by 34.8% (from 18.2% to 53% in 2020 and 2022, respectively), NDM carbapenemases and co-producers of OXA-48, NDM decreased by 25.9% (from 54.5% to 28.6% in 2020 and 2022) and 19.1% (from 27.3% to 8.2% in 2020 and in 2022), respectively. In 2022, strains with the production of KPC carbapenemases and co-producers of carbapenemases of three classes (OXA-48, NDM and KPC) were identified for the first time. Conclusions. The data obtained indicate an increase in the frequency of initial colonization of patients with carbapenem-resistant K. pneumoniae, an expansion of the structure of carbapenemases produced by them, that, if infection control measures are not followed, can increase the frequency of infections caused by them.

Objective. To compare the efficacy of ceftazidime-avibactam and aztreonam combination therapy with “standard” therapy in patients with hematological malignancies and sepsis, caused by carbapenemresistant K. pneumoniae. Materials and Methods. In this open, single center prospective-retrospective, cohort study, during 2019–2022, we analyze medical documentation of 81 hospitalized patients with hematologic malignancies and K. pneumoniae sepsis. K. pneumoniae was identified by MALDI-TOF mass-spectrometry; antimicrobial susceptibility testing was performed in accordance with current versions of EUCAST guidelines. Patients with sepsis, caused by carbapenem-resistant K. pneumoniae isolates (n = 53), received either ceftazidimeavibactam plus aztreonam combined therapy (1st group, n = 26), or “standard” antimicrobial therapy (2nd group, n = 27). Results. K. pneumoniae sepsis was diagnosed in 81 patient with hematologic malignancies during 3 years study period. In 53 (65.4%) cases sepsis was caused by carbapenem-resistant K. pneumoniae isolates. Mortality in patients that received combination therapy with ceftazidime-avibactam and aztreonam was significantly lower (34.6%), than in patients that received other antimicrobial therapy (63.0%), p = 0.039. When ceftazidime-avibactam plus aztreonam therapy was started ≥7 days after the onset of infection the mortality rates in both groups were similar (p > 0.05). Conclusions. The incidence of carbapenem-resistance in K. pneumoniae sepsis in hematologic malignancies was 65.4% in the present study. Early administration of ceftazidime-avibactam and aztreonam combined therapy was associated with lower mortality (34.6%) comparing alternative antibiotic regimens (63.0%).

Many bacterial genomes carry prophages whose induction can eliminate competitors. In response, bacteria may become resistant by modifying surface receptors, by lysogenization, or by other poorly known processes. All these mechanisms affect bacterial fitness and population dynamics. To understand the evolution of phage resistance, we co-cultivated a phage-sensitive strain (BJ1) and a polylysogenic Klebsiella pneumoniae strain (ST14) under different phage pressures. The population yield remained stable after 30 days. Surprisingly, the initially sensitive strain remained in all populations and its frequency was highest when phage pressure was strongest. Resistance to phages in these populations emerged initially through mutations preventing capsule biosynthesis. Protection through lysogeny was rarely observed because the lysogens have increased death rates due to prophage induction. Unexpectedly, the adaptation process changed at longer time scales: the frequency of capsulated cells in BJ1 populations increased again because the production of the capsule was fine-tuned, reducing the ability of phage to absorb. Contrary to the lysogens, these capsulated-resistant clones are pan-resistant to a large panel of phages. Intriguingly, some clones exhibited transient non-genetic resistance to phages, suggesting an important role of phenotypic resistance in coevolving populations. Our results show that interactions between lysogens and sensitive strains are shaped by antagonistic co-evolution between phages and bacteria. These processes may involve key physiological traits, such as the capsule, and depend on the time frame of the evolutionary process. At short time scales, simple and costly inactivating mutations are adaptive, but in the long term, changes drawing more favorable trade-offs between resistance to phages and cell fitness become prevalent.

The more frequent usage of colistin resulted in an increase of colistin resistance due to lipopolysaccharide modifications. The aim of this study was to reveal the prevalence and mechanisms of colistin resistance among multidrug-resistant Klebsiella pneumoniae isolates collected in Bulgaria. One hundred multidrug resistant K. pneumoniae isolates were collected in a period between 2017 and 2018. Among them, 29 colistin resistant and 8 heteroresistant isolates were observed and further investigated. Clonal relatedness was detected by RAPD and MLST. Сarbapenemases, two component system phoQ / phoP , pmrA/B , and mgrB were investigated by PCR amplification and Sanger sequencing. Among 37 colistin nonsusceptible isolates, we detected 25 NDM-1 producers. The isolates belonged mainly to ST11 (80%), and also to ST147, ST35, ST340, ST219 (1-2 members per clone). Nine colistin resistant isolates showed changes in mgrB. IS903B-like elements truncated mgrB in five isolates. In two isolates, premature stopcodon (Q30stopcodon) was observed and another two isolates did not amplify mgrB , possibly due to bigger deletion or insertion. No isolates showed pho Q/ pho P and pmr A/B mutations except for pmrB (four isolates had R256G). All isolates with IS903B insertions belonged to ST11 clone. The mgrB alterations play major role in colistin resistance in K. pneumoniae isolates studied in the current work. We report truncation of mgrB by IS903 like element in colistin resistant NDM-1 producing K. pneumoniae ST11 clone in Bulgaria. [ABSTRACT FROM AUTHOR]

Mohamed A El-Mokhtar, 1 Khaled M Hassanein, 1 Ahmed S Ahmed, 1 Gamal FM Gad, 2 Mohamed M Amin, 3 Osama FE Hassanein 4 1Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut, Egypt; 2Department of Microbiology and Immunology, Faculty of Pharmacy, Minia University, Minia, Egypt; 3Department of Microbiology and Immunology, Faculty of Medicine, Aswan University, Aswan, Egypt; 4Drug Research Center, Assiut University, Assiut, EgyptCorrespondence: Mohamed A El-MokhtarDepartment of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut 71515, EgyptTel +20 122 111 53 13Email elmokhtarma@aun.edu.egAim: This study aimed to describe the inhibitory activity of cell-free supernatants (CFS) of lactobacilli against extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae (K pneumoniae) and Pseudomonas aeruginosa (P aeruginosa).Material and Methods: Pathogenic clinical strains of K pneumoniae and P aeruginosa were isolated from urine samples and selected for investigation. Anti-bacterial activities of the CFS of lactobacilli were assessed by agar well diffusion, MTT assay, as well as time-kill tests. In addition, the antibiofilm characteristics were analyzed by the microplate method against fresh and 24 h-old biofilms. The ability of CFS to interfere with bacterial invasion was analyzed by flow cytometry.Results: Although all tested strains were ESBL producers and showed a multidrug-resistant phenotype, the CFS displayed a high anti-ESBL activity with inhibition zone diameters greater than 13 mm in the agar well diffusion assays against both pathogens. The growth kinetics of K pneumoniae and P aeruginosa were dramatically decreased in the presence of the CFS. The CFS not only inhibited the biofilm formation by these pathogens but also was able to remove the 24-h formed biofilms. The invasion abilities of FITC-labelled K pneumoniae decreased from 30.3%± 7 to 15.4%± 5 and invasion of FITC-labelled P aeruginosa was reduced from 36.9%± 7 to 25.2%± 5.Conclusion: CFS of lactobacilli exhibit anti-ESBL activities, which suggests its potential application for controlling or preventing colonization of infections caused by ESBL-producing bacteria.Keywords: lactobacilli, antibiofilm, ESBL, K pneumoniae, P aeruginosa

Abstract Background The aim of this study is to evaluate the risk factors for colonisation by multidrug resistant (MDR) K. pneumoniae in a critical care unit and the relationship between colonisation and the antibiotic pressure exerted by the antimicrobial treatments received by patients. Methods A prospective observational was designed. Patients admitted for more than 48 h to an intensive care unit were included. Samples for surveillance cultures were obtained from all the patients upon admission and once a week. The association between risk factors and colonisation by MDR K. pneumoniae was determined by logistic regression. A Cox regression model was used to evaluate the effect of the use of antimicrobials on the colonisation rate. An ARMIA model was used to investigate the association between the incidence of colonisation by MDR strains and the global consumption of antimicrobials in the unit. Results One thousand seven hundred twenty-five patients were included, from which 308 (17.9%) were positive for MDR K. pneumoniae. In the multivariate analysis, hospitalisation for longer than 7 days together with respiratory infection and administration of any antibiotic was associated with increased MR K. pneumoniae colonisation. Patients who received antibiotics for more than 48 h were colonised earlier than patients who did not receive antibiotic treatment [HR: 2.16 (95%CI:1.55–3.03)]. The ARIMA model found a significant association between the monthly colonisation rate for MR K. pneumoniae and the consumption of cephalosporins and carbapenems in the previous month. Conclusion Individual antibiotic administration and the global antibiotic pressure of cephalosporins and carbapenems are associated to an increased colonisation by MDR K. pneumoniae strains.

Background & aims: Pyogenic liver abscesses (PLA) are space‐occupying lesions in the liver that produce high morbidity and mortality. The clinical characteristics and prognosis of abscesses is different depending on the bacterial culture results and require different strategies for management. The aim of this study was to investigate the clinical characteristics and prognostic factors of patients with PLA. Methods: Clinical features, laboratory tests and etiology of PLA between 2006 to 2011 and 2012 to 2017 in a single hospital were retrospectively reviewed. The incidence and mortality of PLA caused by Escherichia coli and Klebsiella pneumoniae were compared and the risk factors for multiple organ dysfunction (MODS) and endophthalmitis were evaluated. Results: Among the 1,572 PLA patients, the proportion with PLA increased from 333 (21.2%) in 2006‐2011 to 1,239 (78.8%) in 2012‐2017 without any investigation and treatment procedure differences. K pneumoniae was the main isolate in analysed pus cultures (85.6%). The mortality rate of patients with K pneumoniae infection was lower in the latter period (6.7% vs 0.7%, P =.035). Multivariate analyses revealed that age, fever, MODS and length of hospital stay were factors affecting poor prognosis (death + unhealed/uncured) in PLA patients after treatment and that cardiovascular disease, pleural effusion and pulmonary infection were risk factors for MODS, while diabetes mellitus was the only risk factor for endophthalmitis. Most patients (95.5%) with PLA recovered after abscess drainage/puncture and antibiotic therapy. Conclusions: Pleural effusion, fever, MODS and length of hospital stays were factors useful in predicting PLA outcomes. [ABSTRACT FROM AUTHOR]

Background: Hospital-acquired infections caused by K pneumoniae are difficult to eradicate since K pneumoniae carries resistance genes for many antimicrobials, including carbapenems. The study aimed to determine the prevalence of hospital-acquired infections caused by multiple drug-resistant K pneumoniae and identify carbapenem and fluoroquinolone resistance by phenotypic and genotypic methods amongst hospitalised patients.Methods: Two hundred and fifty samples from patients with hospital-acquired infections were included. Identification and susceptibility testing for K pneumoniae isolates was performed by standard methods. The detection of carbapenemase resistance (blaKPC , blaVIM-1 and blaOXA-48 ) and plasmid-mediated quinolone resistance (PMQR; qnrA, qnrB and qnrS) genes was performed using PCR assay.Results: Out of 250 samples, 42 (16.8%) were multiple drug-resistant K pneumoniae, and the frequency of K Pneumoniae isolation was higher in urine samples, in the age group (<10 years), in ICU and in patients with longer hospital stay. Twenty-four (57%) of the isolates were resistant to Meropenem, 13 (31%) were resistant to Imipenem and 35 (83.3%) were resistant to Ciprofloxacin. blaOXA-48 gene was detected in 9 (21.4%) of isolates, and blaVIM-1 gene was detected in 6 (14.3%) of isolates. However, no isolate harboured blaKPC gene. PMQR genes were detected in 100% of ciprofloxacin resistant isolates, and qnrS was the dominant.Conclusion: Multidrug-resistant K pneumoniae isolates harbouring blaOXA-48, blaVIM-1 and PMQR genes are emerging in hospitals particularly with long hospital stays. [ABSTRACT FROM AUTHOR]

Background Extended-spectrum β-lactamase (ESBL)–producing pathogens represent increasing challenges to physicians because of rising prevalence, high mortality, and challenging treatment. Identifying high risks and early appropriate therapy is critical to favorable outcomes. Methods This is a 5-year retrospective case-case-control study performed at the Detroit Medical Center on adult patients with bloodstream infection (BSI) caused by ESBL-producing and non-ESBL–producing Escherichia coli or Klebsiella pneumoniae , each compared with uninfected controls. Data were collected from December 2004-August 2009. Multivariate analysis was performed using logistic regression. Results Participants included 103 patients with BSI caused by ESBL-producing pathogens and 79 patients with BSI caused by pathogens that did not produce ESBLs. The mean age of patients in the ESBL group was 67 years; of the patients, 51% were men, 77% were black, and 38% (n = 39) died in hospital. The mean age of patients in the non-ESBL group was 58 years; of the patients, 51% were men, 92% were black, and 22% (n = 17) died in hospital. On multivariate analysis, predictors of BSI caused by ESBL-producing pathogens included central venous catheter (odds ratio [OR], 29.4; 95% confidence interval [CI], 3.0-288.3), prior β-lactam–/β-lactamase–inhibitor therapy (OR, 28.1; 95% CI, 1.99-396.5), and prior cefepime therapy (OR, 22.7; 95% CI, 2.7-192.4). The only risk factor for BSI caused by non-ESBL–producing pathogens was urinary catheter insertion (OR, 18.2; 95% CI, 3.3-100.3). Conclusion Prior antimicrobial therapy, particularly with β-lactam, was the strongest unique risk factor for BSI caused by ESBL-producing E coli or K pneumoniae . [ABSTRACT FROM AUTHOR]

Goal: This work aims to describe and explore the circumstances of appearance of Klebsiella pneumoniae producing OXA-48 carbapenemase, which has occurred in a neonatal intensive care service at the Mohammed VI University Hospital of Marrakech. Results: During February 2015, the alert was triggered by the isolation of 6 isolates of K pneumoniae with the same antibiotic susceptibility profile in the neonatal intensive care service, suggesting a possible outbreak. Blood cultures represented the main site of isolation of these isolates. The phenotypic study of the isolates made it possible to identify a strain of K pneumoniae susceptible to third-generation cephalosporins, ciprofloxacin, and aminoglycosides, and resistant to ertapenem, β-lactamases inhibitors (ticarcillin-clavulanate, piperacillin-tazobactam; amoxicillin-clavulanic acid), and cotrimoxazole. The genotypic study of the epidemic isolate revealed the presence of the blaOXA-48 gene. The action to be taken was the establishment of corrective measures to stop this epidemic to a multi-resistant germ transmitted by hand transmission. The reinforcement of hygiene measures and the awareness of the staff made it possible to put an end to the epidemic at March 30, 2015, without closing the service. The outcome of 6 infected newborns was fatal due to the fragile terrain and the inappropriate probabilistic antibiotic therapy. Conclusion: The production of carbapenemase in K pneumoniae is an emerging resistance mechanism that must be suspected and identified to offer targeted therapy and to limit its spread. The implementation of a local policy to control multidrug-resistant germs is essential to limit their dissemination in hospitals. [ABSTRACT FROM AUTHOR]