Search

Klebsiella invasive syndrome is a rare condition that typically presents as a liver abscess with metastatic infection, with mortality rates as high as 14% potentially due to diagnostic delay by clinicians. Here, we present a case of a woman in her 60s, who presented with symptoms and signs consistent with meningitis, imaging findings suggestive of possible leptomeningeal carcinomatosis a long with areas of lung consolidation and abdominal nodules and lymphadenopathy, presumably metastatic malignancy. We diagnosed Klebsiella invasive syndrome and treated it conservatively with medical management, including a long course of intravenous antibiotic therapy and supportive care. This is an infrequently encountered clinical entity with potentially fatal consequences, and we hope to add to the existing literature on the subject and drive home the point that it should be considered in the differential diagnoses in the appropriate clinical scenario.

Routine blood culture is used for the detection of bloodstream infections by aerobic and anaerobic bacteria and by common pathogenic yeasts. A retrospective study was conducted in a public hospital in Maceió-AL, by collecting data of all medical records with positive blood cultures. Out of the 2,107 blood cultures performed, 17% were positive with Staphylococcus coagulase negative (51.14%), followed by Staphylococcus aureus (11.21%) and Klebsiella pneumoniae (6.32%). Gram-positive bacteria predominated among positive blood cultures, highlighting the group of Staphylococcus coagulase-negative. While Gram-negative bacteria had a higher number of species among positive blood cultures. Resumo A cultura sanguínea de rotina é usada para a detecção de infecções na corrente sanguínea por bactérias aeróbias e anaeróbias e por leveduras patogênicas comuns. Estudo retrospectivo realizado em hospital público de Maceió-AL, por meio da coleta de dados de todos os prontuários com culturas sanguíneas positivas. Das 2.107 culturas sanguíneas realizadas, 17% foram positivas com Staphylococcus coagulase negativo (51,14%), seguido por Staphylococcus aureus (11,21%) e Klebsiella pneumoniae (6,32%). As bactérias Gram-positiva predominaram entre as culturas de sangue positivas, destacando-se o grupo das Staphylococcus coagulase-negativo. Enquanto as bactérias Gram-negativas apresentaram um número maior de espécies entre as culturas de sangue positivas.

This study compared the antibacterial activity of honey-garlic and honey-ginger mixtures against two clinically important bacteria frequently implicated in acute wound infections;Pseudomonas aeruginosaandKlebsiella pneumoniae. Individual extracts of honey, ginger, garlic and erythromycin antibiotics (positive control), were also tested. Concentrations of 100%, 75%, 50%, and 25% of the natural extracts and mixtures were prepared by the use of sterilized distilled water as the solvent. The antibacterial activity of each natural extract and the antibiotic was tested against the aforementioned bacterial species at different concentrations using the disc diffusion method. Further, MIC and MBC tests were conducted on each natural mixture using the broth dilution method and spread plate method, respectively. Our results showed garlic exhibited the highest antibacterial activity against both bacteria at 100% concentration, whereas honey and ginger showed the lowest antibacterial activity againstKlebsiella pneumoniaeandPseudomonas aeruginosa,respectively at 25% concentrations. Honey-garlic mixture was the most effective againstKlebsiella pneumoniae, whereas honey-ginger mixture was the most effective againstPseudomonas aeruginosa. The antibiotic was more effective than the natural mixtures againstPseudomonas aeruginosa, but not so effective againstKlebsiella pneumoniae. The MIC of both mixtures againstPseudomonas aeruginosaranged from 25%-50%, while it ranged from 6%-50% forKlebsiella pneumoniae. Honey-garlic was the only mixture againstKlebsiella pneumoniaethat exhibited bactericidal effects at 50% (MBC).&nbsp

Klebsiella pneumoniae is a major pathogen of bacterial liver abscess in Asia. Particularly, patients with community-acquired Klebsiella pneumoniae liver abscess (CA-KPLA) tend to have a higher risk of invasive infection and pulmonary is a common invasive infectious site, making it a global clinical crisis. Therefore, considerable attention should be focused on the early prediction and active treatment strategies of such patients.The clinical data of 127 CA-KPLA cases hospitalized from January 2017 to February 2022 were collected from a single center. Risk factors were analyzed by the use of univariable and multivariable analysis. Furthermore, independent risk factors of pulmonary affection were utilized to construct a predictive nomogram.The incidence of pulmonary affection in KPLA patients was 57.5% (73/127) and the majority manifested as nodular lesions with cavities and pleural effusion in chest CT images. Based on the predictive nomogram, the SOFA score (2) was defined as the most dominant independent risk factor for the occurrence of pulmonary affection, followed by the maximum diameter of liver abscess (3 cm), multiple liver abscesses, bacteremia, and badly-controlled diabetes sequentially. The validation of this nomogram also demonstrated good discriminative ability and satisfactory consistency. Finally, early drainage of liver abscess, initial combinational antibiotics, and early Carbapenem-including antibiotic usage were established as favorable factors for therapy in pulmonary affected CA-KPLA patients.This study provided an effective model for the early prediction of pulmonary affection in patients with CA-KPLA and some rational strategies for their early therapeutic remission.

Klebsiella pneumoniae has been identified as one of the important pathogens involved in the pathogenesis of urinary tract infections (UTIs) in humans. This study sought to determine the prevalence of K. pneumoniae and its ability to produce extended-spectrum-β-lactamases (ESBLs) in patients with UTIs. Besides, the predictive significance of interleukin (IL)-15 in UTIs caused by ESBLs-producing K. pneumoniae (K-ESBLs) was also assessed.: During October 2020 – January 2021, a cross-sectional and case-control study was performed on 587 patients with UTIs. Serum level of IL-15 was assessed using an enzyme-linked immunosorbent assay kit. The prevalence of K. pneumonia was 15.8%. It was also found that 68.8% of the K. pneumonia isolates were K-ESBLs (64patients). IL-15 levels were significantly elevated in serum of UTI patients with K-ESBLs compared to 24 control subjects (29.4 ± 9.2 vs. 22.1 ± 5.1; p-value

Primary lung abscess as a complication of necrotising community-acquired pneumonia due to multidrug-resistant (MDR)

Various disorders can cause acute onset ataxia including those that have toxic/metabolic, traumatic, neoplastic, vascular, demyelinating/dysmyelinating, infectious, postinfectious and genetic features. We present a case of postseptic acute ataxia. A 72-year-old woman was diagnosed with septic shock secondary to acute obstructive suppurative cholangitis. A blood sample for bacterial culture was positive for

The appearance of Klebsiella pneumoniae strains producing extended-spectrum β-lactamase (ESBL), and carbapenemase (KPC) has turned into a significant public health issue. ESBL- and KPC-producing K. pneumoniae’s ability to form biofilms is a significant concern as it can promote the spread of antibiotic resistance and prolong infections in healthcare facilities. A total of 45 K. pneumoniae strains were isolated from human infections. Antibiograms were performed for 17 antibiotics, ESBL production was tested by Etest ESBL PM/PML, a rapid test was used to detect KPC carbapenemases, and resistance genes were detected by PCR. Biofilm production was detected by the microtiter plate method. A total of 73% of multidrug resistance was found, with the highest resistance rates to ampicillin, trimethoprim–sulfamethoxazole, cefotaxime, amoxicillin-clavulanic acid, and aztreonam. Simultaneously, the most effective antibiotics were tetracycline and amikacin. blaCTX-M, blaTEM, blaSHV, aac(3)-II, aadA1, tetA, cmlA, catA, gyrA, gyrB, parC, sul1, sul2, sul3, blaKPC, blaOXA, and blaPER genes were detected. Biofilm production showed that 80% of K. pneumoniae strains were biofilm producers. Most ESBL- and KPC-producing isolates were weak biofilm producers (40.0% and 60.0%, respectively). There was no correlation between the ability to form stronger biofilms and the presence of ESBL and KPC enzymes in K. pneumoniae isolates.

The objective of this study was to assess the in vitro activity of ceftazidime-avibactam (CAZ-AVI) and a panel of comparator agents against isolates of Enterobacter spp., Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa collected in 2018 and 2019 by different centres worldwide from patients with respiratory tract infections.Susceptibility and minimum inhibitory concentration (MIC) of all organisms were determined using broth microdilution methodology for CAZ-AVI, and a panel of comparator antimicrobial agents by a central reference laboratory according to Clinical and Laboratory Standards Institute guidelines and European Committee on Antimicrobial Susceptibility Testing guidelines.CAZ-AVI demonstrated potent antimicrobial activity against isolates of Enterobacter spp. (97.6% susceptibility, MICGram-negative respiratory isolates collected in 2018-2019 showed high susceptibility to CAZ-AVI; CAZ-AVI represents a potential treatment option against infection caused by these organisms.

The pathomechanisms underlying the frequently observed fatal outcome of Klebsiella pneumoniae pneumonia in elderly patients are understudied. In this study, we examined the early antibacterial immune response in young mice (age 2–3 mo) as compared with old mice (age 18–19 mo) postinfection with K. pneumoniae. Old mice exhibited significantly higher bacterial loads in lungs and bacteremia as early as 24 h postinfection compared with young mice, with neutrophilic pleuritis nearly exclusively developing in old but not young mice. Moreover, we observed heavily increased cytokine responses in lungs and pleural spaces along with increased mortality in old mice. Mechanistically, Nlrp3 inflammasome activation and caspase-1–dependent IL-1β secretion contributed to the observed hyperinflammation, which decreased upon caspase-1 inhibitor treatment of K. pneumoniae–infected old mice. Irradiated old mice transplanted with the bone marrow of young mice did not show hyperinflammation or early bacteremia in response to K. pneumoniae. Collectively, the accentuated lung pathology observed in K. pneumoniae–infected old mice appears to be due to regulatory defects of the bone marrow but not the lung, while involving dysregulated activation of the Nlrp3/caspase-1/IL-1β axis.

Background Klebsiella pneumoniae is a gram-negative opportunistic pathogen that causes diseases mostly in immunocompromised individuals. Recently, hypervirulent K. pneumoniae strains also cause severe disease in healthy individuals. Capsular polysaccharide (CPS) is the major virulence determinant in hypervirulent K. pneumoniae and protects the cell against the bactericidal activity of the immune system. Gallic acid (GA), a natural phenolic compound, is known to exhibit wide spectrum antibacterial activity; however, its effect on hypervirulent K. pneumoniae remains largely unresolved. We aimed to identify the effects of GA on CPS biosynthesis in hypervirulent K. pneumoniae. Methods Antibacterial activity of GA was evaluated by counting colonies. CPS amount was determined by glucuronic acid content. The transcriptions of cps gene cluster were measured by quantitative real time PCR (qRT-PCR) and the β-galactosidase activity. The effect of GA on the resistance of K. pneumoniae to streptonigrin (SNG), an iron-activated antibiotic, was evaluated. The effect of GA on the resistance of K. pneumoniae to serum killing and phagocytosis by macrophages was observed. Results GA inhibited the growth and CPS biosynthesis in K. pneumoniae. GA may affect the iron availability in K. pneumoniae, thus possibly repressing the cps transcription. In addition, GA reduced the resistance of K. pneumoniae to serum killing and enhanced its susceptibility to phagocytosis. Conclusion GA possesses bactericidal activity and inhibits the CPS biosynthesis in hypervirulent K. pneumoniae, thereby facilitating pathogen clearance by the host immune system. Therefore, GA may represent a promising strategy for the prevention or treatment of patients with hypervirulent K. pneumoniae infections.

Introduction: The broth microdilution (BMD) method recommended for the detection of colistin resistance is labor-intensive, time-consuming, and difficult to apply in routine laboratories. Thus, various methods, such as disk elution, commercial microdilution, and rapid polymyxin-NP tests have been developed for the detection of colistin resistance. In this study, a total of 102 multi-resistant Gram-negative bacteria isolated from blood cultures were evaluated by four different methods for the detection of colistin resistance, and compared with the reference method. Methodology: For the detection of the compatibility of these methods with the reference method, categorical and essential agreements, very major, major, and minor error rates were determined. Colistin-tigecycline and colistin-meropenem combinations were investigated in colistin-resistant isolates. Results: Of the isolates, 15 (15%) [K. pneumoniae (n = 12), A. baumannii (n = 2), E. coli (n = 1)] were resistant to colistin with reference BMD method. MIC50 and MIC90 values of all isolates were ≤ 0.25 μg/mL and 16 μg/mL, respectively. The categorical agreement rates were 100% for commercial microdilution, disk elution, and RPNP test. The essential agreement rates of commercial microdilution, disk elution, and broth macrodilution were 78.4%, 86.3%, and 100%, respectively. Although there were no major errors in these methods, the macrodilution (12%) and commercial microdilution (20.6%) methods showed the most minor errors. Colistin-meropenem combination showed a 100% synergistic effect, but the colistin-tigecycline combination showed an 80% synergistic effect and 20% indifference effect. Conclusions: Disk elution and RPNP tests are suitable for routine use because they are the most efficient, easiest, low-cost, and good performance tests in detecting colistin resistance.

Surveillance of carbapenem-resistant Enterobacterales (CRE) carriers is the first measure of hospital infection control. Screening of CRE carriage can be assessed through culture and molecular techniques, each with specific properties of turnaround-times, sensitivity and specificity.This was a prospective study in a 1200-bed university hospital in Genoa, Italy, where CRE screening is performed analysing cultures from rectal swabs. Our 18-months intervention was to extend the incubation time of the corresponding plates from 48 to 288 h, after reporting negative tests, to evaluate the possible impact on the cultures.A total of 362 patients giving 19,278 swabs and corresponding plates were included. After baseline incubation, plate positivity was 3%, while after the overall lengthened times it was 3.7%. Extended incubation was associated with change in the relative frequency of the most represented species. In particular, we observed reduced presence of total and resistant Klebsiella pneumoniae strains (P0.001) and increased presence of Enterobacter cloacae complex, total and sensitive (P0.001). By extending incubation time, a reduced frequency of overall Enterobacterales strains with high resistance to ertapenem (MIC ≥4 mg/L) was also found (P=0.005), particularly that of K. pneumoniae (P0.001), while the presence of E. cloacae complex increased among organisms with low resistance levels to ertapenem (P0.001).Extending the incubation time of the cultures increased the number of CREs grown, and expanded the bacterial scenario of rectal colonization through the recovery of poorly resistant strains and otherwise undetected species.

Antibiotic resistance has become one of the largest pitfalls of modern medicine, and this has fueled the search for a safe and effective alternative. Of these alternatives, bacteriophage (phage) therapy has emerged as a potential option since it is capable of destroying pathogenic bacteria, without disrupting commensal bacterial populations. Although numerous studies have shown its efficacy in various conditions such as dysentery, sepsis, and meningitis, very little research has focused on its prospective usage to treat dermatological conditions. This review discusses the emerging phage therapy studies surrounding infections caused by Cutibacterium acnes (C. acnes), Staphylococcus aureus (S. aureus), Pseudomonas aeruginosa (P. aeruginosa), and Klebsiella pneumoniae (K. pneumoniae). Phage therapy shows major potential for future usage in the field of dermatology, yet further research must be performed to assure safety and efficacy in humans. J Drugs Dermatol. 2022;21(12):1311-1315. doi:10.36849/JDD.6638.

BACKGROUND: Viet Nam has high rates of antimicrobial resistance (AMR) but little capacity for genomic surveillance. This study used whole genome sequencing to examine the prevalence and transmission of three key AMR pathogens in two intensive care units (ICUs) in Hanoi, Viet Nam. METHODS: A prospective surveillance study of all adults admitted to ICUs at the National Hospital for Tropical Diseases and Bach Mai Hospital was done between June 19, 2017, and Jan 16, 2018. Clinical and environmental samples were cultured on selective media, characterised with MALDI TOF mass spectrometry, and sequenced with Illumina. Phylogenies based on the de-novo assemblies (SPAdes) were constructed with MAFFT (PARsnp), Gubbins, and RAxML. Resistance genes were detected with Abricate against the US National Center for Biotechnology Information database. FINDINGS: 3153 Escherichia coli, Klebsiella pneumoniae, and Acinetobacter baumannii isolates from 369 patients were analysed. Phylogenetic analysis revealed predominant lineages within A baumannii (global clone 2, sequence types ST2 and ST571) and K pneumoniae (ST15, ST16, ST656, ST11, and ST147) isolates. Isolation from stool was most common with E coli (87·0%) followed by K pneumoniae (62·5%). Of the E coli, 85·0% carried a blaCTX-M variant, while 81·8% of K pneumoniae isolates carried blaNDM (54·4%), or blaKPC (45·1%), or both. Transmission analysis with single nucleotide polymorphisms identified 167 clusters involving 251 (68%) of 369 patients, in some cases involving patients from both ICUs. There were no clear differences between the lineages or AMR genes recovered between the two ICUs. INTERPRETATION: This study represents the largest prospective surveillance study of key AMR pathogens in Vietnamese ICUs. Clusters of closely related isolates in patients across both ICUs suggests recent transmission before ICU admission in other health-care settings or in the community. FUNDING: UK Medical Research Council Newton Fund, Viet Nam Ministry of Science and Technology, Wellcome Trust, Academy of Medical Sciences, Health Foundation, and UK National Institute for Health and Care Research Cambridge Biomedical Research Centre.

Recent emergence of high-level tigecycline resistance is mediated by tet(X) genes in Gram-negative bacteria, which undoubtedly constitutes a serious threat for public health worldwide. This study aims to identify tigecycline non-susceptible isolates and detect the presence of genes that are responsible for tigecycline resistance among local isolates in Iraq for the first time.Thirteen clinical isolates of Klebsiella pneumonia, Acinetobacter baumannii and Pseudomonas aeruginosa tigecycline non-susceptible were investigated from blood, sputum and burns specimens. The susceptibility of different antibiotics was tested by the VITEK-2 system. To detect tigecycline resistance genes, PCR was employed.Strains studied in this work were extremely drug-resistant and they were resistant to most antibiotic classes that were studied. The plasmid-encoded tet(X), tet(X1), tet(X2), tet(X3), tet(X4), tet(X5), tet(M) and tet(O) genes were not detected in the 13 isolates. The results showed that there is a clear presence of tet(A) and tet(B) genes in tigecycline non-susceptible isolates. All 13 (100%) tigecycline non-susceptible K. pneumoniae, A. baumannii and P. aeruginosa isolates harbored the tet(B) gene. In contrast, 4 (30.77%) tigecycline non-susceptible P. aeruginosa isolates harbored the tet(A) gene and there was no tigecycline non-susceptible A. baumannii isolate harboring the tet(A) gene (0%), but one (7.69%) tigecycline non-susceptible K. pneumoniae isolate harbored the tet(A) gene. A phylogenetic tree, which is based on the nucleotide sequences of the tet(A) gene, showed that the sequence of the local isolate was 87% similar to the nucleotide sequences for all the isolates used for comparison from GenBank and the local isolate displayed genetic diversity.According to this study, tet(B) and tet(A) play an important role in the appearance of tigecycline non-susceptible Gram-negative isolates.

Amaç: Çoklu ilaç dirençli Gram negatif bakterilerin tedavisi küresel anlamda önemli bir halk sağlığı sorunudur. Karbapenemlere dirençli Klebsiella pneumoniae bu grupta yer alan en önemli patojenlerden biridir. Bu çalışmada karbapenemlere dirençli ve duyarlı K. pneumoniae izolatlarının çeşitli antibiyotiklere direnç durumlarının karşılaştırılması ve tedaviye yol gösterici olunması amaçlanmıştır.Yöntem: Çeşitli klinik örneklerden izole edilmiş 709 karbapenem dirençli, 3029 karbapenem duyarlı 3738 K. pneumoniae izolatının direnç oranları retrospektif olarak incelenmiş, çeşitli antibiyotiklere direnç durumları karşılaştırılmıştır. İzole edilen mikroorganizmaların tanımlanmaları ve antibiyotik duyarlılık testleri VITEK 2 (bioMérieux, Fransa) otomatize sistemi ile yapılmış, sonuçlar European Committee on Antimicrobial Susceptibility Testing (EUCAST) standartlarına göre yorumlanmıştır. Karbapenemlere dirençli izolatlarda seftazidim/ avibaktam duyarlılığı ayrıca disk difüzyon yöntemi ile çalışılmıştır. Kolistin duyarlılığının saptanmasında sıvı mikrodilüsyon yöntemi kullanılmıştır. Antibiyogram sonucu orta derecede duyarlı olanlar, duyarlı olarak kabul edilmiş ve her hastadan birer izolat çalışma kapsamına alınmıştır. Bulgular: Karbapenemlere dirençli K. pneumoniae izolatlarında amikasin, amoksisilin/ klavulanat, aztreonam, sefazolin, sefepim, sefiksim, sefoksitin, seftazidim, seftriakson, sefuroksim, siprofloksasin, kolistin, fosfomisin, gentamisin, levofloksasin, netilmisin, nitrofurantoin, piperasilin/ tazobaktam, trimethoprim/ sulfametaksazol direnç oranları sırası ile %53,12; %99,78; %98,33: %100; %98,26; %97,90; %98,68; %98,57; %98,35; %98,77; %94,63; %16,74; %41,36; %59,32; %92,53; %79,9; %67,02; %99,45; %72.23’ tür ve karbapenemlere duyarlı K. pneumoniae izolatlarına göre anlamlı derecede yüksek bulunmuştur (p, Objective: Treatment of multidrug-resistant Gram-negative bacteria is a global public health problem. Klebsiella pneumoniae resistant to carbapenems is one of the most important pathogens in this group. In this study, it was aimed to compare the resistance status of carbapenem-resistant and susceptible K. pneumoniae isolates to various antibiotics and to guide the treatment.Methods: The resistance rates of 709 carbapenem-resistant and 3029 carbapenem-susceptible 3738 K. pneumoniae isolates isolated from various clinical specimens were retrospectively analysed and their resistance to various antibiotics were compared. Identification of isolated microorganisms and antibiotic susceptibility tests were performed with the VITEK 2 (bioMérieux, France) automated system, and the results were interpreted according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) standards. Ceftazidime/ avibactam susceptibility was also studied by disc diffusion method in isolates resistant to carbapenems. Broth microdilution method was used to determine the sensitivity of colistin. Those who were moderately susceptible as a result of the antibiogram were accepted as susceptible and one isolate from each patient was included in the study.Results: In carbapenem-resistant K. pneumoniae isolates, amikacin, amoxicillin/ clavulanate, aztreonam, cefazolin, cefepime, cefixime, cefoxitin, ceftazidime, ceftriaxone, cefuroxime, ciprofloxacin, colistin, fosfomycin, gentamicin, levofloxacin, netilmicin, nitrofurantoin, piperacillin/ tazobactam, trimethoprim/ sulfamethoxazole resistance rates respectively; 53.12%, 99.78%, 98.33%, 100%, 98.26%, 97.90%, 98.68%, 98.57%, 98.35%, 98.77%, 94.63%, 16.74%, 41.36%, 59.32%, 92.53%, 79.9%, 67.02%, 99.45%, 72.23% and it was found to be significantly higher than K. pneumoniae isolates susceptible to carbapenems (p

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is one of the leading causes of healthcare-associated infections (HAIs) and is particularly pervasive in intensive care units (ICUs). This study takes ICU layout as the research object, and integrates clinical data and bacterial genome analysis to clarify the role of separate, small wards within the ICU in controlling the transmission of CRKP.This study prospectively observed the carriage and spread of CRKP from a long-term in-hospital patient (hereafter called the Patient) colonized with CRKP in the gut and located in a separate, small ward within the ICU. The study also retrospectively investigated CRKP-HAIs in the same ICU. The relationship and transmission between CRKP isolates from the Patient and HAI events in the ICU were explored with comparative genomics.In this study, 65 CRKP-HAI cases occurred during the investigation period. Seven CRKP-HAI outbreaks were also observed. A total of 95 nonrepetitive CRKP isolates were collected, including 32 strains from the Patient in the separate small ward. Phylogenetic analysis based on core genome single-nucleotide polymorphism (cgSNP) showed that there were five possible CRKP clonal transmission events and two clonal outbreaks (A1, A2) during the study. CRKP strains from the Patient did not cause CRKP between-patient transmission or outbreaks in the ICU during the 5-year study period.The presence of a long-term hospitalized patient carrying CRKP and positioned in a separate, small ward did not lead to CRKP transmission or infection outbreaks in the ICU. Combining a small-ward ICU layout with normative HAI control measures for multidrug-resistant pathogen infection was effective in reducing CRKP transmission.

To create an antibiogram derived exclusively from our obstetric population and compare the clinical isolates and susceptibilities to our institutional antibiogram.Data collected by the University Hospital Clinical Microbiology Laboratory in SSC Soft from 01/01/2018 to 12/31/2018 was used to generate our institutional antibiogram. For comparison, we created an obstetric (OB) antibiogram using all clinical isolates collected during the same time interval from OB triage, labordelivery, antepartum and postpartum wards. The antibiotic susceptibilities of the OB clinical isolates were compared to the institutional clinical isolates.In total, we identified 929 clinical isolates from our OB population in 2018. Urine was the predominant source of clinical isolates (76.3%). The remaining sources included wound (10.1%), genital (9.0%), blood and other fluids (4.6%).Compared to our institutional antibiogram, gram-negative clinical isolates in our OB population exhibit less antibiotic resistance. Creation of an OB-specific antibiogram, which more accurately reflects antibiotic resistance patterns within our unique patient population, may promote appropriate antimicrobial use by assisting in more informed antibiotic selection and limit unnecessary use of broad-spectrum antibiotics.

Paenibacterin A1 (PA1) is a broad-spectrum, cationic cyclic lipodepsipeptide antibiotic isolated from

Aims Numerous pre-clinical and clinical studies have recently demonstrated the significant role of phage therapy in treating multidrug-resistant bacterial infections. However, only a few researchers have focused on monitoring the phage-mediated adverse reactions during phage therapy. The present study aimed to demonstrated the oral acute and sub-acute toxicity of bacteriophages (Klebsiella pneumoniae XDR strain) in Charles Foster rats with special reference to immunological response and adverse effects. Methods and Results Bacteriophages were orally administered in dosages of 1010 PFU/ml and a 1015 PFU/ml to Charles Foster rats as a single dose (in acute toxicity study) and daily dosage for 28 days (in sub-acute toxicity study). One millilitre suspension of bacteriophages was administered through the oral gavage feeding tube. No adverse effect was observed in any of the experimental as well as in the control animals. Furthermore, an insignificant change in food and water intake and body weight was observed throughout the study period compared with the control group rats. On the 28th day of phage administration, blood was collected to estimate haematological, biochemical and cytokines parameters. The data suggested no difference in the haematological, biochemical and cytokine profiles compared to the control group. No significant change in any of the treatment groups could be observed on the gross and histopathological examinations. The cytokines estimated, interleukin-1 beta (IL-1β), IL-4, IL-6 and IFN-gamma, were found within the normal range during the experiment. Conclusions The results concluded that no adverse effect, including the severe detrimental impact on oral administration of high (1010 PFU/ml) and very high dose (1015 PFU/ml) of the bacteriophages cocktail. Significance and Impact of Study The high and long-term oral administration of bacteriophages did not induce noticeable immunological response as well.

To effectively contain antimicrobial-resistant (AMR) infections, we must better understand the social determinates of health that contribute to transmission and spread of infections.We used clinical data from patients attending primary healthcare clinics across three jurisdictions of Australia (2007-2019). Escherichia coli (E. coli), Klebsiella pneumoniae (K. pneumoniae), Pseudomonas aeruginosa (P. aeruginosa) and Staphylococcus aureus (S. aureus) isolates and their corresponding antibiotic susceptibilities were included. Using multivariable logistic regression analysis, we assessed associations between AMR prevalence and indices of social disadvantage as reported by the Australian Bureau of Statistics (i.e., remoteness, socio-economic disadvantage and average person per household).This study reports 12 years of longitudinal data from 43 448 isolates from a high-burden low-resource setting in Australia. Access to health and social services (as measured by remoteness index) was a risk factor for increased prevalence of third-generation cephalosporin-resistant (3GC) E. coli (odds ratio 5.05; 95% confidence interval 3.19, 8.04) and methicillin-resistant S. aureus (MRSA) (odds ratio 5.72; 95% confidence interval 5.02, 6.54). We did not find a positive correlation of AMR and socio-economic disadvantage or average person per household indices.Remoteness is a risk factor for increased prevalence of 3GC-resistant E. coli and MRSA. We demonstrate that traditional disease surveillance systems can be repurposed to capture the broader social drivers of AMR. Access to pathogen-specific and social data early and within the local regional context will fill a significant gap in disease prevention and the global spread of AMR.

The emergence and spread of Carbapenem-Resistant Enterobacterales (CRE) has become a growing concern for health services, internationally, nationally, and regionally. In Morocco, the situation is more worrisome as studies on CRE are scarce and/or scattered and/or outdated. As a result, we carried out the present study to determine and update CRE prevalence at Mohammed VI University Hospital of Marrakech, Morocco.A cross-sectional prospective study was carried out from March 2018 to March 2020 on 41161 clinical specimens of 23,469 patients suspected of bacterial infections. Enterobacterales strains were isolated following standard bacteriological procedures. Bacterial strains were identified using BD-Phoenix and MALDI-TOF-MS. Antibiotic susceptibility was determined for 14 antibiotics. Carbapenemase production and phenotypic detection were characterized using modified carbapenem inactivation phenotypic and immunochromatographic methods.All in all, 484 Enterobaterales resistant to at least one carbapenem were recovered. The majority was isolated from the neonatal unit (14%), followed by the urology-nephrology (11%), and plastic surgery departments (10%). K. pneumoniae (n=232) was the most isolated, followed by E. cloacae (n=148), E. coli (n=56), and S. marcescens (n=17). Antibiotic susceptibility profile showed high rates of resistance to ciprofloxacin (75.21%), gentamicin (84.50%), and cotrimoxazole (88.42%). Out of 484 CRE positive cultures, 388 (80.16%) were Carbapenemase-positive. Out of the latter, 170 were metallo-beta-lactamase producers (NDM), 162 OXA-48-like, and 56 both.These findings emphasize the urgent need for control precautions and strict measures to contain and mitigate this issue.

Although Sri Lanka belongs to a region with a high prevalence of extended-spectrum β-lactamase (ESBL), AmpC β-lactamase and carbapenemase-producing Enterobacteriaceae, data regarding antimicrobial resistance (AMR) is limited. We studied the prevalence and diversity of β-lactamases produced by Enterobacteriaceae urinary pathogens from two hospitals in the Western Province of Sri Lanka.ESBL, AmpC β-lactamase and carbapenemase production was detected by phenotypic testing followed by genotyping.The species responsible for urinary tract infections (UTI) were Escherichia coli (69%), Klebsiella pneumoniae (16%) and Enterobacter sp (6%). The prevalence of ESBL (50%), AmpC β-lactamase (19%) and carbapenemase (11%) phenotypes was high, and greater in hospital-acquired (HA-UTI) (75%) than in community-acquired UTI (CA-UTI) (42%). Identification of CA-UTI caused by carbapenemase-producing Enterobacteriaceae (5%) is alarming. Only one ESBL gene, blaThis study adds to the currently scarce data on AMR in Sri Lanka.

Infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) pose a huge health challenge worldwide. The aim of this study was to evaluate the incidence of polymyxin resistance in clinical CRKP isolates in China and to characterize the molecular mechanisms underlying these polymyxin-resistant CRKP (PR-CRKP) isolates.A total of 493 CRKP clinical isolates from patients were collected from six tertiary-care hospitals in China during 2017-2018. Minimum inhibitory concentrations of polymyxin B and colistin were determined using the broth microdilution method. PR-CRKP isolates were identified and subjected to whole-genome sequencing. Quantitative real-time PCR and structural modelling analysis were also performed.We observed a 2.2% (11/493) polymyxin resistance rate in this multicentre cohort. Polymyxin B MICs ranged from 4 to 64 μg/mL and colistin MICs ranged from 8 to 128 μg/mL in 11 PR-CRKP isolates. Key genetic variations identified in PR-CRKP isolates involved eight disruptions (seven insertional inactivation by an insertion sequence [IS] element, one frameshift deletion) in mgrB, and three missense mutations in pmrA, pmrB, and phoP. ISKpn26 was the predominant IS (4/7), and three of these occurred in nucleotide position 74 in the mgrB gene. In addition, we reported a novel mutation S62R in pmrB that may confer polymyxin resistance in K. pneumoniae.Our findings highlight the multifaceted molecular mechanisms of polymyxin resistance in CRKP.

Introduction: We aimed to clarify the genetic background and molecular epidemiology of extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae (K. pneumoniae) at three geographically separated university hospitals in Japan. Methods: From January 2014 to December 2016, 118 ESBL-producing K. pneumoniae (EPKP) strains that were detected and stored at three university hospitals were collected. Molecular epidemiological analysis was performed using enterobacterial repetitive intergenic consensus (ERIC)-polymerase chain reaction (PCR) and multi-locus sequence typing (MLST). The ESBL type was determined using the PCR-sequence method. The presence of plasmid-mediated fluoroquinolone resistance (PMQR) genes was analyzed by PCR. We compared the relationships between PMQR gene possession/quinolone resistance-determining region (QRDR) mutation and levofloxacin (LVFX)/ciprofloxacin (CPFX) susceptibility. Results: The detection rate of EPKP was 4.8% (144/2987 patients). MLST analysis revealed 62 distinct sequence types (STs). The distribution of STs was diverse, and only some EPKP strains had the same STs. ERIC-PCR showed discriminatory power similar to that of MLST. The major ESBL genotypes were CTX-M-15-, CTX-M-14-, and SHV-types, which were detected in 47, 30, and 27 strains, respectively. Ninety-one out of 118 strains had PMQR genes and 14 out of 65 strains which were not susceptible to CPFX had QRDR mutations, and the accumulation of PMQR genes and QRDR mutations tended to lead to higher minimum inhibitory concentrations (MICs) of LVFX. Conclusions: At three geographically separated university hospitals in Japan, the epidemiology of EPKP was quite diverse, and no epidemic strains were found, whereas CTX-M-14 and CTX-M-15 were predominant.

Introduction: We sought to evaluate secondary infections (SIs) in patients admitted to the intensive care unit (ICU) for COVID-19 with respect to incidence, causative pathogens, and clinical outcomes. Methodology: In this two-centre retrospective study, we analysed 146 patients (96 males, 50 females; median age, 64 years) admitted to the ICU with COVID-19 between March 26 and December 31, 2020. Inclusion criteria were an ICU admission for at least 48 hours and age beyond 18 years. Patients with and without SIs were compared and the impacts of SIs and carbapenem resistance on mortality were analysed. Results: During ICU admission, 84 episodes of SIs developed in 58 patients (39.7%). A total of 104 isolates were recovered, with Gram-negative bacteria most frequent accounting for 74%. At least one carbapenem-resistant pathogen (n = 61) was recovered in 41 patients (70.1%). In multivariate analysis, the use of ECMO and an elevated procalcitonin level were significantly associated with the development of SIs. The mortality rate and the incidence of carbapenem resistance did not differ significantly in COVID-19 patients with and without SIs (p = 0.059 and p = 0.083, respectively). Conclusions: The incidences of SIs and carbapenem resistance among COVID-19 patients were alarming, emphasizing stricter infection control measures in the ICU setting. © 2022 Journal of Infection in Developing Countries. All rights reserved.

Objectives Infections due to carbapenem-resistant Enterobacterales are considered urgent public health threats and often treated with a β-lactam/β-lactamase inhibitor combination. However, clinical treatment failure and resistance emergence have been attributed to inadequate dosing. We used a novel framework to provide insights of optimal dosing exposure of ceftazidime/avibactam. Methods Seven clinical isolates of Klebsiella pneumoniae producing different KPC variants were examined. Ceftazidime susceptibility (MIC) was determined by broth dilution using escalating concentrations of avibactam. The observed MICs were characterized as response to avibactam concentrations using an inhibitory sigmoid Emax model. Using the best-fit parameter values, %fT>MICi was estimated for various dosing regimens of ceftazidime/avibactam. A hollow-fibre infection model (HFIM) was subsequently used to ascertain the effectiveness of selected regimens over 120 h. The drug exposure threshold associated with bacterial suppression was identified by recursive partitioning. Results In all scenarios, ceftazidime MIC reductions were well characterized with increasing avibactam concentrations. In HFIM, bacterial regrowth over time correlated with emergence of resistance. Overall, suppression of bacterial regrowth was associated with %fT>MICi ≥ 76.1% (100% versus 18.2%; P Conclusions An optimal drug exposure to suppress KPC-producing bacteria was identified. The novel framework is informative and may be used to guide optimal dosing of other β-lactam/β-lactamase inhibitor combinations. Further in vivo investigations are warranted.

Objectives: Nosocomial pneumonia is a common complication in critically ill patients. The goal of this study was to examine the efficacy of the Toll-like receptor 4 agonist 3-deacyl phosphorylated hexacyl disaccharide (3D PHAD), in a clinically relevant murine model of pneumonia, and assess the cellular mechanisms that mediate the protective response. Design: Mice received intrapulmonary 3D PHAD (20 μg) or vehicle for 2 consecutive days before challenge with intrapulmonary Klebsiella pneumoniae (2.3 × 10 3 colony-forming units). Mice were followed for 14-day survival, pulmonary K. pneumoniae burden, lung leukocyte profile, leukocyte phagocytic capacity, and cytokine production. Pneumonia severity and leukocyte recruitment were further assessed by histological evaluation. Setting: Research laboratory. Subjects: Wild-type, male C57BL/6 J mice. Interventions: Intrapulmonary treatment with 20 μg 3D PHAD for 2 consecutive days. Measurements and main results: Intrapulmonary treatment with 3D PHAD decreased lung K. pneumoniae colony-forming units and pneumonia severity with an associated improvement in survival compared with mice treated with vehicle. The numbers of neutrophils, monocytes, and macrophages in the lungs of 3D PHAD-treated mice were higher than those in vehicle-treated mice before infection but were not significantly different from vehicle-treated mice at 48 h after K. pneumoniae challenge. Lung innate leukocytes from 3D PHAD-treated mice had increased phagocytic capacity. Treatment with 3D PHAD alone increased cytokines in the lungs but decreased cytokines in plasma during K. pneumoniae pneumonia as compared with control. Conclusions: Intrapulmonary treatment with 3D PHAD augments innate immunity in the lung and facilitates resistance to K. pneumoniae pneumonia.

The role of Klebsiella pneumoniae (KP) in lower respiratory tract infection (LRTI) is not well studied. We longitudinally investigated KP colonization and its association with LRTI in a South African birth cohort.We conducted a case-control study of infants who developed LRTI and age-matched controls, followed twice weekly through infancy. Nasopharyngeal swabs taken fortnightly and at LRTI for 33-multipex Quantitative multiplex real-time polymerase chain reaction were tested at LRTI and twice weekly from 90 days preceding LRTI. Controls were tested over the equivalent period. Multivariate models investigated the factors associated with LRTI or with KP-associated LRTI (KP-LRTI).Among 885 infants, there were 439 LRTI episodes, of which 68 (15.5%) were KP-LRTI (OR 1.93; 95% CI 1.25-3.03). Infants with KP-LRTI were younger than those without KP-LRTI (median [IQR] 3.7 [2.1-5.9] vs 4.7 [2.8-7.9] months, P-value=0.009). Clinical features of KP and non-KP-LRTI were similar with 114 (26%) infants hospitalized. Prematurity (adjusted odds ratio [aOR] 11.86; 95% CI 5.22-26.93), HIV exposure (aOR 3.32; 95% CI 1.69-6.53), lower birthweight (aOR 0.68; 95% CI 0.51-0.91), and shorter breastfeeding time (aOR 0.79; 95% CI 0.65-0.96) were associated with KP-LRTI versus non-LRTI. These factors and younger age were associated with KP-LRTI versus non-KP-LRTI.KP was associated with a substantial proportion of LRTI, particularly in premature or HIV-exposed infants in whom strategies for treatment and prevention should be strengthened.

Klebsiella pneumoniae is one of the major pathogens causing global multidrug-resistant infections. Therefore, strategies for preventing and controlling the infections are urgently needed. Phage depolymerase, often found in the tail fiber protein or the tail spike protein, is reported to have antibiofilm activity. In this study, phage P560 isolated from sewage showed specific for capsule locus type KL47 K. pneumoniae, and the enlarged haloes around plaques indicated that P560 encoded a depolymerase. The capsule depolymerase, ORF43, named P560dep, derived from phage P560 was expressed, purified, characterized and evaluated for enzymatic activity as well as specificity. We reported that the capsule depolymerase P560dep, can digest the capsule polysaccharides on the surface of KL47 type K. pneumoniae, and the depolymerization spectrum of P560dep matched to the host range of phage P560, KL47 K. pneumoniae. Crystal violet staining assay showed that P560dep was able to significantly inhibit biofilm formation. Further, a single dose (50 μg/mouse) of depolymerase intraperitoneal injection protected 90%-100% of mice from lethal challenge before or after infection by KL47 carbapenem-resistant K. pneumoniae. And pathological changes were alleviated in lung and liver of mice infected by KL47 type K. pneumoniae. It is demonstrated that depolymerase P560dep as an attractive antivirulence agent represents a promising tool for antimicrobial therapy.

Antimicrobial resistance (AMR) is a global threat that requires serious attention, particularly when it is developed against colistin, which is considered one of the 'last-resort' antibiotics for curing an infection. This study aimed to investigate the AMR profile of the Klebsiella (K.) pneumoniae clinical isolates and to obtain the comprehensive characteristics of the carbapenemases among the carbapenem-resistant K. pneumoniae (CR-KP) when isolated. In addition, to detect the colistin resistance and investigate the MCR genes in the clinical K. pneumoniae isolates for the first time in Jordan.A total of 179 K. pneumoniae isolates were cultured and they were confirmed using the VITEK 2 system and PCR. The antibiotic susceptibilities, extended-spectrum beta-lactamase (ESβL), multidrug-resistant (MDR), and CR-KP were determined by using the VITEK 2 system, disc diffusion, and the minimum inhibitory concentration (MIC) test. PCR was performed to detect the MCR and carbapenemase genes.The rates of ESβL, MDR, and CR-KP were 48 %, 62 %, and 12.8 %, respectively. High colistin resistance of 49.7 % (89/179) was found. Only one MCR-1 (1.1 %) out of the 89 colistin resistance isolates was detected. Many of the isolates harbored the ESβL genes. In particular, the carbapenem genes were detected in 26 isolates, with 46 % KPC enzyme genes (12/26), 23 % IMP genes (6/26), 19 % OXA-48 genes (5/26), 11.5 % NDM-1 genes (3/26) but no VIM gene was found. The statistical analyses revealed a significant association between colistin resistance and MDR (P ≤ 0.05, Chi-square test). An association between colistin resistance and the Piperacillin, Ceftazidime, Cefpodoxime, Imipenem, Aztreonam, and Tobramycin resistance was noted.The study's findings demonstrated the presence of the MCR-1 gene in the K. pneumoniae clinical isolates for the first time in Jordan and indicated that the KPC and IMP encoded carbapenemases were the most prevalent K. pneumoniae carbapenemases in Jordan patients.

Few population-level estimates of invasive neonatal infections have been reported from sub-Saharan Africa. We estimated the national incidence risk, aetiology, and pathogen antimicrobial susceptibility for culture-confirmed neonatal bloodstream infections and meningitis in South Africa.We conducted a cross-sectional study of neonates (28 days of life) admitted to neonatal or paediatric wards of 256 public sector health facilities in South Africa during 2014-19. Diagnostic pathology records from Jan 1, 2014, to Dec 31, 2019, were extracted from a national pathology data warehouse. A case was defined as a neonate with at least one positive blood or cerebrospinal fluid culture during a 14-day period. Incidence risk was calculated using annual numbers of registered livebirths. Among the causative pathogens identified, we calculated the proportion of cases attributed to each of them, as well as the rates of antibiotic susceptibility of Gram-positive and Gram-negative bacteria.Among 43 438 records of positive cultures, there were 37 631 incident cases of neonatal infection with at least one pathogen isolated. The overall incidence risk of culture-confirmed infections was 6·0 per 1000 livebirths (95% CI 6·0-6·1). The incidence risk of late-onset sepsis (days 3-27 of life) was 4·9 per 1000 livebirths (4·9-5·0) and that of early-onset sepsis (days 0-2 of life) was 1·1 per 1000 livebirths (1·1-1·1); risk ratio 4·4 (95% CI 4·3-4·5). The cause of infection differed by syndrome, timing of infection onset, facility, and province, although Klebsiella pneumoniae (26%), Acinetobacter baumannii (13%), and Staphylococcus aureus (12%) were the dominant pathogens overall. Gram-negative bacteria had declining susceptibility to most antibiotics over the study period.We found a high incidence risk of late-onset sepsis with provincial variations, predominance of K pneumoniae, and declining antibiotic susceptibility among Gram-negative bacteria. This national surveillance in an upper-middle-income country provides a baseline burden of neonatal infections against which the impact of future clinical and public health interventions can be measured.BillMelinda Gates Foundation.

Patients with acute uncomplicated pyelonephritis often show impaired immune function that aggravates infectious diseases. Some of the therapeutic recommendations for UTIs have been revised recently, partly because of the emergence of antibiotic resistant bacteria such as quinolone-resistant Escherichia coli and Extended spectrum beta-lactamase (ESBL) producing bacteria, mainly E. coli and Klebsiella pneumoniae, which vary from country to country or between regions in frequency of emergence and spread. An era of antimicrobial resistance (AMR) has arrived, where the use of antibiotics should be reconsidered. Several newly established antimicrobial agents are commercially available for the treatment of resistant bacteria, such as penicillins or cephalosporins with beta-lactamase inhibitors. This new edition of Asian Association of UTISTI (AAUS) guideline for acute uncomplicated pyelonephritis includes new recommendations for antibiotic use based on changing trends in antibiotic resistance.

Two urease operons were identified in Klebsiella pneumoniae CG43, ure-1 and ure-2. This study investigates whether a differential regulation of the expression of ure-1 and ure-2 exists and how urease activity influences the acid stress response and expression of type 1 and type 3 fimbriae.The ureA1 and ureA2 gene specific deletion mutants were constructed. Promoter activity was assessed using a LacZ reporter system. The sensitivity to acid stress was determined by assessing the survival after pH 2.5 treatment. The influence on type 1 and type 3 fimbriae expression was assessed using western blotting and mannose-sensitive yeast agglutination and biofilm formation assay, respectively.Bacterial growth analysis in mM9-U or modified Stuart broth revealed that ure-1 was the principal urease system, and ure-2 had a negative effect on ure-1 activity. Deletion of the fur or nac gene had no apparent effect on the activity of Pure-1 is the primary expression system in K. pneumoniae CG43, while ure-2 is active in the absence of hns. Impairment of urease activity increases the sensitivity to acid stress, and the accumulation of urea induces the expression of type 1 fimbriae but represses type 3 fimbriae expression.

Meningitis due to resistant microorganisms after neurosurgical intervention progresses with significant morbidity and mortality. Treatment is difficult as the antibiotics available for this purpose as well as their transition to the cerebrospinal fluid are limited. Due to the inability of the intravenously administered colistin to cross the blood–brain barrier sufficiently, intraventricular colistin application is recommended in the treatment of meningitis. Herein we report successful treatment with intraventricular colistin of an infant with ventriculoperitoneal shunt-related meningitis due to extended spectrum β-lactamase-producing Klebsiella pneumoniae. The infant lacked clinical response despite effective intravenous antibiotic therapy. Intrathecal/intraventricular colistin can be an effective alternative in the treatment of resistant Gram-negative bacilli meningitis.

Introduction: Secondary Bacterial Infections (SBIs) of the respiratory system are one of the biggest medical concerns in patients undergoing hospitalization with a diagnosis of COVID-19. This study aims to provide relevant data for the initiation of appropriate empirical treatment after examining the etiology and antimicrobial resistance of SBIs in COVID-19 patients under care in the Intensive Care Units (ICUs) in the largest pandemic hospital of our country. Methodology: Between March 16, 2020 and December 31, 2021, 56,993 COVID patients were hospitalized, of which 7684 were admitted to ICUs. A total of 1513 patients diagnosed with SBIs have been included in this study. During the course of the study, demographic data, clinical course, etiology and antimicrobial resistance data of all patients were collected. Results: The most common causative agents of SBIs were inferred as Acinetobacter baumanii (35.1%), Staphylococcus aureus (15.2%), Klebsiella pneumoniae (12.3%) and Pseudomonas aeruginosa (10.4%). The isolation rates of carbapenem-resistant and colistin-resistant A. baumannii, K. pneumoniae and P. aeruginosa were 83.7%; 42.7%, 79.2%, and 5.6%, 42.7%, 1.7%, respectively. Acinetobacter pittii clustering was seen in one of the ICUs in the hospital. Multidrug resistant 92 (5.4%) Corynebacterium striatum isolates were also found as a causative agent with increasing frequency during the study period. Conclusions: SBI of the respiratory system is one of the major complications in patients hospitalized with COVID-19. The antimicrobial resistance rates of the isolated bacteria are generally high, which indicates that more accurate use of antibacterial agents is necessary for SBIs in patients hospitalized with COVID-19 diagnosis.

Carbapenem-resistant Enterobacterales (CRE) infection is highly endemic in China; Klebsiella pneumoniae carbapenemase (KPC) 2-producing CRE is the most common, whereas KPC-3-producing CRE is rare. We report an outbreak of KPC-3-producing Enterobacterales infection in China. During August 2020-June 2021, 25 bla

To assess the current prevalence, distribution, and main clonal types of carbapenem-resistant Enterobacterales (CRE) in the United Arab Emirates.A total of 504 CRE collected over a 9-month period in 15 hospitals were studied. Antibiotic susceptibility and the presence of common carbapenemase, 16S methylase, and mobile colistin resistance genes were assessed. Selected strains forming larger clusters by pulsed field gel electrophoresis were subjected to whole genome sequencing to identify their sequence types and core genome MLST.Strains expressing OXA and NDM type carbapenemases and 16S methylases were present in all major hospitals. Considerable interhospital differences were noticed, suggesting the role of specific clones. A total of three major Klebsiella pneumoniae clones (CC14, ST231, and CC147) were identified, accounting for 48.6% of all CRE. All clones were significantly more resistant than sporadic isolates. CC14 strains exhibited a significant association with Emirati patients.Nearly half of CRE infections in the country are due to a limited number of clones. The data indicate the possibility of interhospital transmission, combined in some hospitals with inadequate stewardship practices. The study also revealed an association of the largest, most resistant clone (CC14) with Emirati patients. The specific reasons for it should be clarified by further investigations.

Aims: This study was aimed to identify compounds with significant inhibitory potential against multidrug-resistant (MDR), multidrug-sensitive and clinical isolates of Klebsiella pneumoniae. Materials & methods: Antibacterial activity of the nitroquinoline derivatives was assessed by micro-plate Alamar Blue assay. Results: Nitroquinoline derivatives 9, 11 and 14 showed inhibitory activity against MDR K. pneumoniae. Docking studies of these compounds with topoisomerase IV of K. pneumonia indicated the interactions of these compounds at the active site residues of enzyme near to cofactor (Mg+2). Furthermore, compound 11 was identified as a reactive oxygen species (ROS) inducer. None of the compounds showed hemolytic effect. Conclusion: This study was designed to identify compounds active against MDR K. pneumoniae which causes infections, such as pneumonia and urinary tract infections.

Bolničke infekcije predstavljaju jedan od važnijih izazova u medicini u 21. stoljeću, a multirezistentni mikroorganizmi se ističu kao njihovi glavni uzročnici. Među njima je Klebsiella pneumoniae, emergentna patogena bakterija koja u formi biofilma može kontaminirati bolničko okruženje čija je eradikacija sa standardnim dezinficijensima vrlo teška. Stoga se posljednjih godina razvijaju nove moderne tehnologije suzbijanja biofilmova s ciljem postizanja asepse u bolničkom okruženju. Kao jedna od učinkovitih metoda pokazala se primjena plinovitog ozona budući da ozon posjeduje jaka antimikrobna svojstva i visoki oksidacijski potencijal. Cilj ovog rada bio je utvrditi učinkovitost plinovitog ozona na redukciju broja bakterija u biofilmu pet kliničkih i jednog standardnog soja K. pneumoniae tijekom 60-minutne izloženosti ozonu te kvantificirati količinu biofilma prije i nakon tretmana koristeći različite metode detekcije. Biofilmovi svih ispitivanih sojeva stvoreni su na keramičkim pločicama dimenzija 2,5 cm x 2,5 cm tijekom 24h koji su zatim izloženi djelovanju ozona kroz 1h. Nakon ispiranja, određen je ukupan broj kultivabilnih bakterija, izmjerena je biološka aktivnost te ukupna biomasa nakon bojenja kristal-violetom. Analizom pretražnim elektronskim mikroskopom vizualizirana je destrukcija biofilma. Plinoviti ozon pokazao se vrlo učinkovitim te statistički značajnim u uništavanju stvorenih bakterijskih biofilmova na keramičkim pločicama. Tretman ozonom je uzrokovao smanjenje ukupnog broja kultivabilnih bakterija do 2,63log10CFU/cm2 te smanjio količinu ukupne biomase do 67,17%. Postotci inhibicije varirali su od 36,61% do 99,76%, ovisno o korištenoj metodi kvantifikacije. Sve metode korištene u ovom istraživanju učinkovite su u određivanju inhibicije stvaranja biofilma plinovitog ozona, no potrebna su dodatna istraživanja kako bi se ispitao združeni učinak s drugim metodama dezinfekcije., Hospital-acquired infections represent one of the most important challenges in medicine in the 21st century, and multi-resistant microorganisms stand out as their main causative agents. Among them is Klebsiella pneumoniae, an emerging and pathogenic bacterium that can contaminate the hospital environment in the form of a biofilm, whose eradication with standard disinfectants is very difficult. Therefore, in recent years, new modern biofilm suppression technologies have been developed with the aim of greater microbiological purity. One of the most effective methods is the application of gaseous ozone since ozone has strong antimicrobial properties and a high oxidation potential. The aim of this work was to determine the effectiveness of gaseous ozone in reducing the number of bacteria in the biofilm of five clinical and one standard strain of K. pneumoniae during a 60-minute exposure to ozone and to quantify the amount of biofilm before and after treatment using different methods. Biofilms of all tested strains were created on ceramic plates measuring 2.5 cm x 2.5 cm for 24 hours, which were then exposed to ozone for 1 hour. After washing, the total number of cultivable bacteria was determined, biological activity and total biomass were measured after staining with crystal violet. Analysis with a scanning electron microscope visualized the destruction of the biofilm. Gaseous ozone proved to be very effective and statistically significant in destroying the created bacterial biofilms on ceramic tiles. Ozone treatment caused a decrease in the total number of cultivable bacteria to 2.63log10CFU/cm2, followed by a decrease in total biomass to 67.17%. The inhibition percentages varied from 36.61% to 99.76%, depending on the quantification method used. All methods used in this research are effective in determining the ability of gaseous ozone against biofilms, but additional research is required.

Introduction: Klebsiella pneumoniae is a major pathogen implicated in healthcare-associated infections. Extended-spectrum β-lactamase (ESBL) and carbapenemase-producing K. pneumoniae isolates are a public health concern. This study investigated the existence of some ESBL and carbapenemase genes among clinical isolates of K. pneumoniae in Southwest Nigeria and additionally determined their circulating clones. Materials and Methods: Various clinical samples from 420 patients from seven tertiary hospitals within Southwestern Nigeria were processed between February 2018 and July 2019. These samples were cultured on blood agar and MacConkey agar, and the isolated bacteria were identified by Microbact GNB 12E. All K. pneumoniae were confirmed by polymerase chain reaction (PCR) using the 16s rRNA gene. Antibiotic susceptibility testing (AST) was done on these isolates, and the PCR was used to evaluate the common ESBL-encoding genes and carbapenem resistance genes. Genotyping was performed using multi-locus sequencing typing (MLST). Results: The overall prevalence of K. pneumoniae in Southwestern Nigeria was 30.5%. The AST revealed high resistance rates to tetracyclines (67.2%), oxacillin (61.7%), ampicillin (60.2%), ciprofloxacin (58.6%), chloramphenicol (56.3%), and lowest resistance to meropenem (43.0%). All isolates were susceptible to polymyxin B. The most prevalent ESBL gene was the TEM gene (47.7%), followed by CTX-M (43.8%), SHV (39.8%), OXA (27.3%), CTX-M-15 (19.5%), CTX-M-2 (11.1%), and CTX-M-9 (10.9%). Among the carbapenemase genes studied, the VIM gene (43.0%) was most detected, followed by OXA-48 (28.9%), IMP (22.7%), NDM (17.2%), KPC (13.3%), CMY (11.7%), and FOX (9.4%). GIM and SPM genes were not detected. MLST identified six different sequence types (STs) in this study. The most dominant ST was ST307 (50%, 5/10), while ST258, ST11, ST147, ST15, and ST321 had (10%, 1/10) each. Conclusion: High antimicrobial resistance in K. pneumoniae is a clear and present danger for managing infections in Nigeria. Additionally, the dominance of a successful international ST307 clone highlights the importance of ensuring that genomic surveillance remains a priority in the hospital environment in Nigeria.

International audience; Klebsiella pneumoniae (Kp), a human gut colonizer and opportunistic pathogen, is a major contributor to the global burden of antimicrobial resistance. Virulent bacteriophages represent promising agents for decolonization and therapy. However, the majority of anti-Kp phages that have been isolated thus far are highly specific to unique capsular types (anti-K phages), which is a major limitation to phage therapy prospects due to the highly polymorphic capsule of Kp. Here, we report on an original anti-Kp phage isolation strategy, using capsule-deficient Kp mutants as hosts (anti-Kd phages). We show that anti-Kd phages have a broad host range, as the majority are able to infect noncapsulated mutants of multiple genetic sublineages and O-types. Additionally, anti-Kd phages induce a lower rate of resistance emergence in vitro and provide increased killing efficiency when in combination with anti-K phages. In vivo, anti-Kd phages are able to replicate in mouse guts colonized with a capsulated Kp strain, suggesting the presence of noncapsulated Kp subpopulations. The original strategy proposed here represents a promising avenue that circumvents the Kp capsule host restriction barrier, offering promise for therapeutic development.IMPORTANCE Klebsiella pneumoniae (Kp) is an ecologically generalist bacterium as well as an opportunistic pathogen that is responsible for hospital-acquired infections and a major contributor to the global burden of antimicrobial resistance. In the last decades, limited advances have been made in the use of virulent phages as alternatives or complements to antibiotics that are used to treat Kp infections. This work demonstrates the potential value of an anti-Klebsiella phage isolation strategy that addresses the issue of the narrow host range of anti-K phages. Anti-Kd phages may be active in infection sites in which capsule expression is intermittent or repressed or in combination with anti-K phages, which often induce the loss of capsule in escape mutants.

In this study, we determined the presence of virulence factors in nonoutbreak, high-risk clones and other isolates belonging to less common sequence types associated with the spread of OXA-48-producing Klebsiella pneumoniae clinical isolates from The Netherlands (n = 61) and Spain (n = 53). Most isolates shared a chromosomally encoded core of virulence factors, including the enterobactin gene cluster, fimbrial fim and mrk gene clusters, and urea metabolism genes (ureAD). We observed a high diversity of K-Locus and K/O loci combinations, KL17 and KL24 (both 16%), and the O1/O2v1 locus (51%) being the most prevalent in our study. The most prevalent accessory virulence factor was the yersiniabactin gene cluster (66.7%). We found seven yersiniabactin lineages-ybt 9, ybt 10, ybt 13, ybt 14, ybt 16, ybt 17, and ybt 27-which were chromosomally embedded in seven integrative conjugative elements (ICEKp): ICEKp3, ICEKp4, ICEKp2, ICEKp5, ICEKp12, ICEKp10, and ICEKp22, respectively. Multidrug-resistant lineages-ST11, ST101, and ST405-were associated with ybt 10/ICEKp4, ybt 9/ICEKp3, and ybt 27/ICEKp22, respectively. The fimbrial adhesin kpi operon (kpiABCDEFG) was predominant among ST14, ST15, and ST405 isolates, as well as the ferric uptake system kfuABC, which was also predominant among ST101 isolates. No convergence of hypervirulence and resistance was observed in this collection of OXA-48-producing K. pneumoniae clinical isolates. Nevertheless, two isolates, ST133 and ST792, were positive for the genotoxin colibactin gene cluster (ICEKp10). In this study, the integrative conjugative element, ICEKp, was the major vehicle for yersiniabactin and colibactin gene clusters spreading. IMPORTANCE Convergence of multidrug resistance and hypervirulence in Klebsiella pneumoniae isolates has been reported mostly related to sporadic cases or small outbreaks. Nevertheless, little is known about the real prevalence of carbapenem-resistant hypervirulent K. pneumoniae since these two phenomena are often separately studied. In this study, we gathered information on the virulent content of nonoutbreak, high-risk clones (i.e., ST11, ST15, and ST405) and other less common STs associated with the spread of OXA-48-producing K. pneumoniae clinical isolates. The study of virulence content in nonoutbreak isolates can help us to expand information on the genomic landscape of virulence factors in K. pneumoniae population by identifying virulence markers and their mechanisms of spread. Surveillance should focus not only on antimicrobial resistance but also on virulence characteristics to avoid the spread of multidrug and (hyper)virulent K. pneumoniae that may cause untreatable and more severe infections.

In this study, we determined the presence of virulence factors in nonoutbreak, high-risk clones and other isolates belonging to less common sequence types associated with the spread of OXA-48-producing Klebsiella pneumoniae clinical isolates from The Netherlands (n = 61) and Spain (n = 53). Most isolates shared a chromosomally encoded core of virulence factors, including the enterobactin gene cluster, fimbrial fim and mrk gene clusters, and urea metabolism genes (ureAD). We observed a high diversity of K-Locus and K/O loci combinations, KL17 and KL24 (both 16%), and the O1/O2v1 locus (51%) being the most prevalent in our study. The most prevalent accessory virulence factor was the yersiniabactin gene cluster (66.7%). We found seven yersiniabactin lineages-ybt 9, ybt 10, ybt 13, ybt 14, ybt 16, ybt 17, and ybt 27-which were chromosomally embedded in seven integrative conjugative elements (ICEKp): ICEKp3, ICEKp4, ICEKp2, ICEKp5, ICEKp12, ICEKp10, and ICEKp22, respectively. Multidrug-resistant lineages-ST11, ST101, and ST405-were associated with ybt 10/ICEKp4, ybt 9/ICEKp3, and ybt 27/ICEKp22, respectively. The fimbrial adhesin kpi operon (kpiABCDEFG) was predominant among ST14, ST15, and ST405 isolates, as well as the ferric uptake system kfuABC, which was also predominant among ST101 isolates. No convergence of hypervirulence and resistance was observed in this collection of OXA-48-producing K. pneumoniae clinical isolates. Nevertheless, two isolates, ST133 and ST792, were positive for the genotoxin colibactin gene cluster (ICEKp10). In this study, the integrative conjugative element, ICEKp, was the major vehicle for yersiniabactin and colibactin gene clusters spreading. IMPORTANCE Convergence of multidrug resistance and hypervirulence in Klebsiella pneumoniae isolates has been reported mostly related to sporadic cases or small outbreaks. Nevertheless, little is known about the real prevalence of carbapenem-resistant hypervirulent K. pneumoniae since these two phenomena are often separately studied. In this study, we gathered information on the virulent content of nonoutbreak, high-risk clones (i.e., ST11, ST15, and ST405) and other less common STs associated with the spread of OXA-48-producing K. pneumoniae clinical isolates. The study of virulence content in nonoutbreak isolates can help us to expand information on the genomic landscape of virulence factors in K. pneumoniae population by identifying virulence markers and their mechanisms of spread. Surveillance should focus not only on antimicrobial resistance but also on virulence characteristics to avoid the spread of multidrug and (hyper)virulent K. pneumoniae that may cause untreatable and more severe infections.