Prevalence of Potential Virulence Genes in Klebsiella spp. Isolated from Cows with Clinical Mastitis on Large Chinese Dairy Farms.

Klebsiella spp. is a common cause of clinical mastitis (CM) in dairy cows. However, relatively less information is available about distribution of virulence factors of Klebsiella spp. isolated from cows with CM. Objectives of this study were, therefore, to determine the prevalence of hypermucoviscosity (HMV) phenotype, capsule serotypes, and potential virulence genes in Klebsiella spp. from cows in China with CM. A total of 241 Klebsiella spp. isolates were recovered from cows with CM on 123 dairy farms (each had >500 lactating cows) located in 13 provinces of China. Of the isolates, 124 (51%) and 117 (49%) were identified as Klebsiella pneumoniae and Klebsiella oxytoca, respectively. The prevalence of HMV was 16% for K. pneumoniae and 11% for K. oxytoca; entB (78%), fimH1 (55%), kfu (31%), and mrkD (24%) were the prevalent virulence genes among K. pneumoniae, whereas entB (50%), fimH1 (30%), and mrkD (22%) were prevalent in K. oxytoca. Prevalence of the lac gene was higher for K. pneumoniae (78%) than for K. oxytoca (13%), whereas the nif gene was more prevalent in K. oxytoca than in K. pneumoniae (12% and 1%, respectively). Fifty-six K. pneumoniae isolates were confirmed as K57, the most prevalent capsule serotype (45%). Twenty-one (18%), 20 (10%), and 9 (8%) of 117 K. oxytoca isolates were positive for K57, K5, and K54 serotypes, respectively. As the predominant serotype, K. pneumoniae K57 isolates had a higher prevalence of the HMV phenotype and fimH1 than non-K57 K. pneumoniae. In conclusion, virulence factors were commonly detected for both K. oxytoca and K. pneumoniae causing CM in Chinese dairy herds. HMV isolates were commonly identified, irrespective of species. In addition, as the predominant capsule in bovine K. pneumoniae, the K57 serotype may be better adapted to the udder environment; therefore, further studies targeting pathogenicity to mammary tissue should contribute new knowledge for vaccine development using this serotype.

Etiology of community-onset monomicrobial bacteremic pneumonia and its clinical presentation and outcome: Klebsiella and Pseudomonas matters.

To describe the difference of the clinical features, bacteremia severity, and outcome of patient with community-onset bacteremic pneumonia between Pseudomonas, Klebsiella, and other causative microorganisms, the total 278 adults with community-onset monomicrobial bacteremic pneumonia were studied in a retrospective cohort. Klebsiella (61 patients, 21.9%) and Pseudomonas (22, 7.9%) species was the leading and the fifth common pathogen, respectively. More patients having initial presentation with critical illness (a Pitt bacteremia score ≥ 4) and a fatal comorbidity (McCabe classification) as well as a higher short- (30-day) or long-term (90-day) mortality rate was evidenced in patients infected with Klebsiella or Pseudomonas species, compared to other causative microorganisms. Compared to patients in the Klebsiella group, more frequencies of recent chemotherapy and an initial presentation of febrile neutropenia, and less proportions of diabetes mellitus were disclosed among those in the Pseudomonas group. Of importance, a significantly differential survival curve between Klebsiella or Pseudomonas species and other species during 30-day or 90-day period after bacteremia onset but a similarity of Pseudomonas and Klebsiella species was evidenced, using the Cox-regression after adjusting the independent predictors of 30-day mortality. Conclusively, of pathogens causing community-onset bacteremic pneumonia, Klebsiella and Pseudomonas species should be recognized as the highly virulent pathogens and resulted in poor short- and long-term prognoses.

Modified Carba NP Test: Simple and rapid method to differentiate KPC- and MBL-producing Klebsiella species.

BACKGROUND: The aim of this study was to evaluate the modified Carba NP test to differentiate KPC (Klebsiella pneumoniae carbapenemase)- and MBL (metallo-ß-lactamase)-producing Klebsiella species. METHODS: A total of 508 non-duplicate clinical isolates of Klebsiella spp. were processed by modified Carba NP and combined disc tests which were further confirmed by conventional polymerase chain reaction (PCR), a gold standard method for statistical analysis. RESULTS: Modified Carba NP test demonstrated 91.7% sensitivity, 100% specificity, 100% positive predictive value (PPV) and 99.8% negative predictive value (NPV) for KPC and 96.7%, 100%, 100%, and 99.5% for MBL detection, respectively. CONCLUSION: The performance of modified Carba NP test was significantly better than combined disc test, fulfilling the requirement of simple and rapid test for clinical applications.

Unique Bilaterally Symmetrical Multifocal Osteomyelitis Presentation in a Health-care Worker with Sickle Cell Disease Secondary to Klebsiella Infection - A Case Report.

Introduction: Osteomyelitis is one of the most common infectious complications in people with sickle cell disease (SCD). The most common infecting organisms in SCD are the Salmonella species and Staphylococcus aureus; Streptococcus pneumoniae and Bacteroides species have also been described, however, osteomyelitis attributable to infection with hypervirulent Klebsiella spp. is a rare entity. We describe our experience with a rare presentation of multifocal bilateral symmetrical ulna and fibula osteomyelitis in a patient with SCD due to Klebsiella bacteremia with 1-year follow-up. Case Report: A 25-year-old female known SCD since childhood who underwent treatment for dengue at our hospital had her blood cultures positive for Klebsiella, following which she was treated with appropriate antibiotics. Two weeks following the asymptomatic period patient presented with complaints of pain over the bilateral forearm and legs. The patient was evaluated for laboratory parameters and plain radiograph of the bilateral forearm and bilateral legs. The radiological features were suggestive of osteomyelitis, showing "Bilaterally symmetrical involvement." Laboratory parameters erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were found raised. The patient was planned for biopsy and debridement of the lesion from the right ulna. The culture from the biopsy showed growth of Klebsiella sp. and was sensitive to co-trimoxazole. The patient was started on co-trimoxazole for 6 weeks and had a significant clinical improvement in the form of subsidence of pain, normalization of the blood counts along with the acute phase reactants (ESR, CRP). Conclusion: Our case contributes to the growing awareness of the unusual manifestations of this serious disease and the rarity of bilateral symmetrical involvement. Our case highlights the importance of clinician awareness, manifestations, and management of Klebsiella sp. hypervirulent strains.

Management of Otitis externa with Ayurvedic formulation Gandhak Rasayana- A case report.

Otitis externa is an inflammatory and infectious disease that affects the external auditory canal. The term otorrhea refers to the outflow of discharge from the ear which is one of the main symptoms of otitis externa along with inflammation. External ear canal pathology or middle ear illness with tympanic membrane perforation is the etiological factor of otorrhea. Otorrhea is an indication of infection. Antimicrobial agents are the conventional treatment of various bacterial and fungal infections, but they have impediments such as resistance development, side effects, patient affordability, etc. The Gandhak Rasayana formulation mentioned in the Ayurvedic text can be a good option for the treatment of various infectious diseases. Karnasrava is a type of ear disease referred to as Vata predominant Tridoshaja disease and it is curable. The term Karnasrava signifies discharge from ear and is self-explanatory. Karnasrava consists of a wide spectrum of diseases and can have a near correlation with otitis externa as per signs and symptoms. Gandhak Rasayana exhibited significant antibacterial, antifungal and anti-inflammatory activity in otitis externa. Evaluating its antibacterial and antifungal activity can provide scientific evidence for the study through the present case report. A 31-year-old male patient registered in OPD at Sane Guruji Hospital, Hadapsar, Pune was clinically diagnosed as Karnasrava (Otitis externa) and pus culture positive for Klebsiella species. We started the treatment with Gandhak Rasayana-an Ayurvedic formulation of 250mg two tablets in the morning and evening with lukewarm water for 21 days. The outcome of the treatment was observed as a reduction in Karnashula (otalgia), Karnasrava (ear discharge), Karnakandu (itching), ear blockage and inflammatory changes. Post-treatment culture was negative for the organism. The improvement was noted in Brighton grading scale from grade III to grade I. Gandhak Rasayana showed significant antibacterial activity in the present case. Evaluating its antibacterial, antifungal and anti-inflammatory activity can provide scientific evidence for the study.

Antimicrobial resistance and prevalence of extended-spectrum beta-lactamase-producing Klebsiella species in East Tennessee dairy farms.

Klebsiella species commonly reside in dairy cattle guts and are consistently exposed to beta-lactam antibiotics, including ceftiofur, which are frequently used on the U.S. dairy farms. This may impose selection pressure and result in the emergence of extended-spectrum beta-lactamase (ESBL)-producing strains. However, information on the status and antimicrobial resistance (AMR) profile of ESBL-Klebsiella spp. in the U.S. dairy farms is largely unknown. This study aimed to determine the prevalence and AMR profile of ESBL-Klebsiella spp. and the factors affecting their occurrence in dairy cattle farms. Rectal fecal samples (n = 508) and manure, feed, and water samples (n = 64) were collected from 14 dairy farms in Tennessee. Samples were directly plated on CHROMagar ESBL, and presumptive Klebsiella spp. were confirmed using matrix-assisted laser desorption/ionization-time of flight mass spectrometry. Antimicrobial susceptibility testing was performed on the isolates against panels of 14 antimicrobial agents from 10 classes using minimum inhibitory concentration. Of 572 samples, 57 (10%) were positive for ESBL-Klebsiella spp. The fecal prevalence of ESBL-Klebsiella spp. was 7.2% (95% CI: 6.5-8.0). The herd-level fecal prevalence of ESBL-Klebsiella spp. was 35.7% (95% CI: 12.7-64.8). The fecal prevalence of ESBL-Klebsiella spp. was significantly higher in calves than in cows and higher in cows with higher parity (≥3) as compared to cows with low parity (P < 0.001). Most (96.5%, n = 57) ESBL-Klebsiella spp. were resistant to ceftriaxone. The highest level of acquired co-resistance to ceftriaxone in ESBL-Klebsiella spp. was to sulfisoxazole (66.7%; 38/57). About 19% of ESBL-Klebsiella spp. were multidrug resistant. The presence of ESBL-producing Klebsiella spp. in dairy cattle, feed, and water obtained from troughs could play a crucial epidemiological role in maintaining and spreading the bacteria on farms and serving as a point source of transmission. IMPORTANCE: We collected 572 samples from dairy farms, including rectal feces, manure, feed, and water. We isolated and identified extended-spectrum beta-lactamase (ESBL)-Klebsiella spp. and conducted an antimicrobial susceptibility test and analyzed different variables that may be associated with ESBL-Klebsiella spp. in dairy farms. The results of our study shed light on how ESBL-Klebsiella spp. are maintained through fecal-oral routes in dairy farms and possibly exit from the farm into the environment. We determine the prevalence of ESBL-Klebsiella spp. and their antimicrobial susceptibility profiles, underscoring their potential as a vehicle for multiple resistance gene dissemination within dairy farm settings. We also collected data on variables affecting their occurrence and spread in dairy farms. These findings have significant implications in determining sources of community-acquired ESBL-Enterobacteriaceae infections and designing appropriate control measures to prevent their spread from food animal production systems to humans, animals, and environments.

Bacterial Diversity and Antibiotic Resistance Patterns of Community-Acquired Urinary Tract Infections in Mega Size Clinical Samples of Egyptian Patients: A Cross-Sectional Study.

BACKGROUND:  Community-acquired urinary tract infection (UTI) is one of the most common infectious diseases nowadays. Alarming increased levels of antimicrobial resistance are developing globally which limit treatment options and may lead to life-threatening problems. AIM: Our study aimed to collect surveillance data on non-hospitalized Egyptian UTI cases and to develop strategies against multidrug-resistant pathogens (MDR). According to our knowledge, this is the first study to screen this high number (15,252 urine samples) in a short period (three months), providing valuable data on resistance profiles in non-hospitalized Egyptian UTI patients. METHODS: A total of 15,252 urine samples were collected from different patients. Positive cultures were identified using a semi-quantitative method. Kirby-Bauer's disc diffusion method was used for antibiotic susceptibility testing, the double disc diffusion method was used for extended-spectrum beta-lactamases-producing strains, and the Chi-square test was used for statistical data processing. RESULTS: The results showed 61% positive cultures, females accounted for 67.5%. Infants and elderly patients showed the highest positive cultures (74.4% and 69.2%, respectively). Despite Escherichia coli being the most common uropathogen (47.19%), Klebsiella species(24.42%) were the most MDR and extended-spectrum ß-lactamase (ESBL)-producing organisms. E. coli and Klebsiella spp. displayed increased resistance to cephalosporins (75% and 81%, respectively). In contrast, both organisms displayed high sensitivity to carbapenems. Unlike Klebsiella spp., E. coli was highly sensitive (92%) to first-line treatment (nitrofurantoin) for UTI. Moreover, trimethoprim/sulfamethoxazole showed higher sensitivity rates compared to other nations. CONCLUSION:  Despite Escherichia coli being the most often identified bacteria in our isolates Klebsiella spp. displayed higher resistance to the majority of tested antibiotics. Fortunately, trimethoprim/sulfamethoxazole significantly increased sensitivity, especially against E. coli. However, both species showed high rates of cephalosporin resistance. Moreover, It is important to promote Egypt's national action plan for antimicrobial resistance in collaboration with the World Health Organization, especially in the community to minimize the chance of bacterial resistance in the Egyptian community.

Herd-level relationship between antimicrobial use and presence or absence of antimicrobial resistance in gram-negative bovine mastitis pathogens on Canadian dairy farms.

Concurrent data on antimicrobial use (AMU) and resistance are needed to contain antimicrobial resistance (AMR) in bacteria. The present study examined a herd-level association between AMU and AMR in Escherichia coli (n=394) and Klebsiella species (n=139) isolated from bovine intramammary infections and mastitis cases on 89 dairy farms in 4 regions of Canada [Alberta, Ontario, Québec, and Maritime Provinces (Prince Edward Island, Nova Scotia, and New Brunswick)]. Antimicrobial use data were collected using inventory of empty antimicrobial containers and antimicrobial drug use rate was calculated to quantify herd-level AMU. Minimum inhibitory concentrations (MIC) were determined using Sensititre National Antimicrobial Resistance Monitoring System (NARMS) gram-negative MIC plate (Trek Diagnostic Systems Inc., Cleveland, OH). Isolates were classified as susceptible, intermediate, or resistant. Intermediate and resistant category isolates were combined to form an AMR category, and multivariable logistic regression models were built to determine herd-level odds of AMR to tetracycline, ampicillin, cefoxitin, chloramphenicol, trimethoprim-sulfamethoxazole combination, sulfisoxazole, streptomycin and kanamycin in E. coli isolates. In the case of Klebsiella species isolates, logistic regression models were built for tetracycline and sulfisoxazole; however, no associations between AMU and AMR in Klebsiella species were observed. Ampicillin-intermediate or -resistant E. coli isolates were associated with herds that used intramammarily administered cloxacillin, penicillin-novobiocin combination, and cephapirin used for dry cow therapy [odds ratios (OR)=26, 32, and 189, respectively], and intramammary ceftiofur administered for lactating cow therapy and systemically administered penicillin (OR=162 and 2.7, respectively). Use of systemically administered penicillin on a dairy farm was associated with tetracycline and streptomycin-intermediate or -resistant E. coli isolates (OR=5.6 and 2.8, respectively). Use of cephapirin and cloxacillin administered intramammarily for dry cow therapy was associated with increasing odds of having at least 1 kanamycin-intermediate or -resistant E. coli isolate at a farm (OR=8.7 and 9.3, respectively). Use of systemically administered tetracycline and ceftiofur was associated with cefoxitin-intermediate or -resistant E. coli (OR=0.13 and 0.16, respectively); however, the odds of a dairy herd having at least 1 cefoxitin-intermediate or -resistant E. coli isolate due to systemically administered ceftiofur increased with increasing average herd parity (OR=3.1). Association between herd-level AMU and AMR in bovine mastitis coliforms was observed for certain antimicrobials. Differences in AMR between different barn types and geographical regions were not observed.

Optimization of Empirical Antimicrobial Therapy in Enterobacterales Bloodstream Infection Using the Extended-Spectrum Beta-Lactamase Prediction Score.

Clinical tools for the prediction of antimicrobial resistance have been derived and validated without examination of their implementation in clinical practice. This study examined the impact of utilization of the extended-spectrum beta-lactamase (ESBL) prediction score on the time to initiation of appropriate antimicrobial therapy for bloodstream infection (BSI). The quasi-experimental cohort study included hospitalized adults with BSI due to ceftriaxone-resistant (CRO-R) Enterobacterales at three community hospitals in Columbia, South Carolina, USA before (January 2010 to December 2013) and after (January 2014 to December 2019) implementation of an antimicrobial stewardship intervention. In total, 45 and 101 patients with BSI due to CRO-R Enterobacterales were included before and after the intervention, respectively. Overall, the median age was 66 years, 85 (58%) were men, and 86 (59%) had a urinary source of infection. The mean time to appropriate antimicrobial therapy was 78 h before and 46 h after implementation of the antimicrobial stewardship intervention (p = 0.04). Application of the ESBL prediction score as part of an antimicrobial stewardship intervention was associated with a significant reduction in time to appropriate antimicrobial therapy in patients with BSI due to CRO-R Enterobacterales. Utilization of advanced rapid diagnostics may be necessary for a further reduction in time to appropriate antimicrobial therapy in this population.

Class 1 integrons and multiple mobile genetic elements in clinical isolates of the Klebsiella pneumoniae complex from a tertiary hospital in eastern China.

Background: The emergence of highly drug-resistant K. pneumoniae, has become a major public health challenge. In this work, we aim to investigate the diversity of species and sequence types (STs) of clinical Klebsiella isolates and to characterize the prevalence and structure of class 1 integrons. Methods: Based on the whole genome sequencing, species identification was performed by 16S rRNA gene homology and average nucleotide identity (ANI) analysis. STs were determined in accordance with the international MLST schemes for K. pneumoniae and K. variicola. Integron characterization and comparative genomic analysis were performed using various bioinformatic tools. Results: Species identification showed that the 167 isolates belonged to four species: K. pneumoniae, K. variicola subsp. variicola, K. quasipneumoniae and K. aerogenes. Thirty-six known and 5 novel STs were identified in K. pneumoniae, and 10 novel STs were identified in K. variicola subsp. variicola. Class 1 integrons were found in 57.49% (96/167) of the isolates, and a total of 169 resistance gene cassettes encoding 19 types of resistance genes, including carbapenem resistance gene (bla IPM-4) and class D ß-lactamases gene (bla OXA-1 and bla OXA-10), were identified. Among the 17 complete genomes, 29 class 1 integrons from 12 groups were found, only 1 group was encoded on chromosomes. Interestingly, one plasmid (pKP167-261) carrying two copies of approximately 19-kb IS26-Int1 complex resistance region that contains an integron and a multidrug resistance gene fragment. Conclusion: The results of this work demonstrated that the species and STs of the clinical Klebsiella isolates were more complex by the whole genome sequence analysis than by the traditional laboratory methods. Finding of the new structure of MGEs related to the resistance genes indicates the great importance of deeply exploring the molecular mechanisms of bacterial multidrug resistance.

Urinary Tract Infections and Associated Factors among Patients with Indwelling Urinary Catheters Attending Bugando Medical Centre a Tertiary Hospital in Northwestern Tanzania.

Complications of indwelling urinary catheterization (IUC) are associated with significant morbidity and mortality, thus affecting patient's well-being. Understanding the magnitude and factors associated with complications is crucial in designing appropriate preventive strategies. A cross-sectional study was conducted at Bugando Medical Centre, involving patients with long-term and short-term IUC from December 2016 to September 2017. The data were analyzed by STATA 13.0. Catheter-associated urinary tract infection (CA-UTI) was the leading (56.8%; 250/440) complication among patients with IUC. Gram-negative bacteria were predominantly isolated (98.1%, 252/257), whereas E. coli (30.7%, 79/257) and Klebsiella spp. (29.6%, 76/257) were the leading pathogens. CA-UTI was significantly higher among out-patients than in-patients (82.2% v 35.3%, p < 0.001). Older age (OR: 1.3, (95%CI: 1.1-1.5), p < 0.001), level of education (OR: 1.8, (95%CI: 1.1-3.1), p = 0.029) and catheter duration of ≥6 weeks (OR: 2.43, (95%CI: 1.1-5.5), p = 0.031) independently predicted CA-UTI among outpatients, while female gender (OR: 2.1, (95%CI: 1.2-3.7), p = 0.014), catheter bags not freely hanging (OR: 0.4, (95%CI: 0.2-0.7), p = 0.002) and residing outside Mwanza region (OR: 0.4, (95%CI: 0.2-0.6), p < 0.001) predicted CA-UTI among in-patients. CA-UTI is the common complication among patients with IUC, significantly higher in out-patients than in-patients. We recommend involving patients and carers in infection prevention and control measures in out-patients living with IUC.

Toxic Megacolon Burdened with COVID-19 Coinfection-Worsening of an Unfavorable Diagnosis: A Single-Center Retrospective Study.

INTRODUCTION: This study primarily sought to evaluate the risk factors for toxic megacolon development and treatment outcomes in Clostridium difficile-positive COVID-19 patients, secondarily to determining predictors of survival. METHODS: During the second COVID-19 wave (May 2020 to May 2021), we identified 645 patients with confirmed COVID-19 infection, including 160 patients with a severe course in the intensive care unit. We selected patients with Clostridium difficile infection (CDI) (31 patients) and patients with toxic megacolon (9 patients) and analyzed possible risk factors. RESULTS: Patients who developed toxic megacolon had a higher incidence (without statistical significance, due to small sample size) of cancer and chronic obstructive pulmonary disease, a higher proportion of them required antibiotic treatment using cephalosporins or penicillins, and there was a higher rate of extracorporeal circulation usage. C-reactive protein (CRP) and interleukin-6 values showed significant differences between the groups (CRP [median 126 mg/L in the non-toxic megacolon cohort and 237 mg/L in the toxic megacolon cohort; p = 0.037] and interleukin-6 [median 252 ng/L in the group without toxic megacolon and 1127 ng/L in those with toxic megacolon; p = 0.016]). As possible predictors of survival, age, presence of chronic venous insufficiency, cardiac disease, mechanical ventilation, and infection with Candida species were significant for increasing the risk of death, while corticosteroid and cephalosporin treatment and current Klebsiella infection decreased this risk. CONCLUSIONS: More than ever, the COVID-19 pandemic required strong up-to-date treatment recommendations to decrease the rate of serious in-hospital complications. Further studies are required to evaluate the interplay between COVID-19 and CDI/toxic megacolon.

Prevalence and antimicrobial resistance of Klebsiella species isolated from clinically ill companion animals.

BACKGROUND: Klebsiella spp. is an important conditional pathogen in humans and animals. However, due to the indiscriminate use of antibiotics, the incidence of antimicrobial resistance has increased. OBJECTIVES: The purpose of this study was to investigate antimicrobial resistance in strains of Klebsiella strains and the phylogenetic relatedness of extended-spectrum cephalosporin (ESC)-resistance among Klebsiella strains isolated from clinically ill companion animals. METHODS: A total of 336 clinical specimens were collected from animal hospitals. Identification of Klebsiella species, determination of minimum inhibitory concentrations, detection of ESC resistance genes, polymerase chain reaction-based replicon typing of plasmids by conjugation, and multilocus sequence typing were performed. RESULTS: Forty-three Klebsiella strains were isolated and, subsequently, 28 were identified as K. pneumoniae, 11 as K. oxytoca, and 4 as K. aerogenes. Eleven strains were isolated from feces, followed by 10 from ear, 7 from the nasal cavity, 6 from urine, 5 from genitals, and 4 from skin. Klebsiella isolates showed more than 40% resistance to penicillin, cephalosporin, fluoroquinolone, and aminoglycoside. ESCresistance genes, CTX-M groups (CTX-M-3, CTX-M-15, and CTX-M-65), and AmpC (CMY-2 and DHA-1) were most common in the K. pneumoniae strains. Some K. pneumoniae carrying CTX-M or AmpC were transferred via IncFII plasmids. Two sequence types, ST709 and ST307, from K. pneumoniae were most common. CONCLUSIONS: In conclusion, this is the first report on the prevalence, ESCresistance genotypes, and sequence types of Klebsiella strains isolated from clinically ill companion animals. The combination of infectious diseases and antimicrobial resistance by Klebsiella in companion animals suggest that, in clinical veterinary, antibiotic selection should be made carefully and in conjunction with the disease diagnosis.

Pattern of colistin resistance in Klebsiella isolates in an Intensive Care Unit of a tertiary care hospital in India.

BACKGROUND: Carbapenem resistance among multidrug resistant organism is a growing global concern with high rates being reported from South Asia and Mediterranean countries. It is associated not only with high morbidity and mortality, but also pose a grave health hazard. Among various studies, it has been found that among the gram-negative bacteria Klebsiella species is found to have a high resistance. The aim of the study was to evaluate the prevalence and pattern of colistin resistance in Klebsiella species (spp.) in a tertiary care hospital in India. METHODS: An audit of microbiological data of all Klebsiella spp. isolates from blood, urine, sputum and pus was collected from patients admitted to intensive care unit (ICUs) between 1st January 2015 to 31st December 2017 and the prevalence of Colistin resistance in Klebsiella spp. was calculated. RESULTS: Over a period of thirty six months, 2499 isolates were identified from culture positive specimen of blood, urine, sputum, broncho-alveolar lavage (BAL) fluid and pus from patients admitted to ICU. Among the total isolates 21.32% (n=533) of Klebsiella spp. were isolated and 1.28% (n=30) of isolates were colistin resistant. In patients admitted to ICU, colistin resistant Klebsiella spp. was identified in 8.75% (n=14) of the total blood samples, 4.26% (n=7) in urine samples and 4.4% (n=8) in sputum and BAL samples. CONCLUSION: The prevalence of Colistin resistant Klebsiella spp. was estimated to be 5.6% in our ICU. Colistin resistant Klebsiella is becoming an emerging threat in ICU settings limiting further treatment options. Stringent surveillance and robust antibiotic stewardship program to tide over this crisis is need of the hour.

Targeting the Sugary Armor of Klebsiella Species.

The emergence of multidrug-resistant strains of Gram-negative Klebsiella species is an urgent global threat. The World Health Organization has listed Klebsiella pneumoniae as one of the global priority pathogens in critical need of next-generation antibiotics. Compared to other Gram-negative pathogens, K. pneumoniae accumulates a greater diversity of antimicrobial-resistant genes at a higher frequency. The evolution of a hypervirulent phenotype of K. pneumoniae is yet another concern. It has a broad ecological distribution affecting humans, agricultural animals, plants, and aquatic animals. Extracellular polysaccharides of Klebsiella, such as lipopolysaccharides, capsular polysaccharides, and exopolysaccharides, play crucial roles in conferring resistance against the host immune response, as well as in colonization, surface adhesion, and for protection against antibiotics and bacteriophages. These extracellular polysaccharides are major virulent determinants and are highly divergent with respect to their antigenic properties. Wzx/Wzy-, ABC-, and synthase-dependent proteinaceous nano-machineries are involved in the biosynthesis, transport, and cell surface expression of these sugar molecules. Although the proteins involved in the biosynthesis and surface expression of these sugar molecules represent potential drug targets, variation in the amino acid sequences of some of these proteins, in combination with diversity in their sugar composition, poses a major challenge to the design of a universal drug for Klebsiella infections. This review discusses the challenges in universal Klebsiella vaccine and drug development from the perspective of antigen sugar compositions and the proteins involved in extracellular antigen transport.

Utility of Combination Antimicrobial Therapy in Adults with Bloodstream Infections due to Enterobacteriaceae and Non-Fermenting Gram-Negative Bacilli Based on In Vitro Analysis at Two Community Hospitals.

This study examined the utility of combination therapy for bloodstream isolates of Enterobacteriaceae and non-fermenting Gram-negative bacilli (NFGN) from adults at two community hospitals from January 2010 through to June 2015. Changes to in vitro antimicrobial susceptibilities by adding ciprofloxacin or gentamicin to third-generation cephalosporins (3GC) were examined overall and in patients with risk factors for 3GC resistance. Overall ceftriaxone susceptibility among Enterobacteriaceae was 996/1063 (94%) and 247/295 (84%) in patients with 3GC resistance risk factors. Susceptibilities increased marginally by adding ciprofloxacin or gentamicin (mean difference 2.4% (95% CI 1.5, 3.4) and 3.0% (95% CI 2.0, 4.0), respectively, overall and 5.4% (95% CI 2.8, 8.0) and 7.1% (95% CI 4.2, 10.1), respectively, in patients with risk factors). Eighty-three of 105 (79%) NFGN were susceptible to ceftazidime overall and 20/29 (69%) in patients with prior beta-lactam use. Overall mean increase in susceptibilities was 15.2% (95% CI: 8.3, 22.2) and 17.1% (95% CI: 9.8, 24.5) for ciprofloxacin and gentamicin combinations, respectively; and 27.6% (95% CI: 10.3, 44.9) for either one with recent beta-lactam use. In this setting, empirical combination therapy had limited utility for Enterobacteriaceae bloodstream isolates but provided significant additional antimicrobial coverage to ceftazidime for NFGN, particularly in patients with prior beta-lactam use.

Investigation of risk factors for community-acquired urinary tract infections caused by extended-spectrum beta-lactamase Escherichia coli and Klebsiella species.

PURPOSE: The aim of this study was to determine the prevalence and risk factors for community-acquired urinary tract infections (CA-UTIs) caused by extended-spectrum ß-lactamase (ESBL) producing Escherichia coli and Klebsiella species. MATERIALS AND METHODS: The patients diagnosed with CA-UTIs caused by E. coli or Klebsiella spp. were included in the study. All of the patients were compared to demographic characteristics, underlying diseases, urinary tract pathology, history of hospitalization, use of antibiotics according to ESBL positivity. RESULTS: A total of 322 urine isolates were studied. Sixty-six patients (37.1%) of a total of 178 patients were ESBL positive E. coli and Klebsiella spp. Being over the age of sixty (odds ratio [OR], 1.90; p=0.03), history of renal stone (OR, 3.00; p=0.03), urinary tract anatomical of physiological disorder (OR, 2.17; p=0.01), urologic intervention (OR, 3.43; p<0.001), history of urinary tract surgery (OR, 3.10; p=0.01), history of urinary catheterization (OR, 3.43; p<0.001), and hospitalization for last 1 year (OR, 3.70; p=0.01) and antibiotic usage in the last 3 months (OR, 1.90; p=0.04) were found as significant risk factors for the producing of ESBL. However, gender and underlying disease were not related for ESBL production. CONCLUSIONS: In present study, high rate of ESBL positivity was detected in CA-UTIs. The increasing of infections caused by ESBL positive E. coli and Klebsiella spp. are bringing together a lot of the problem, such as antibiotic resistance and reducing treatment options for outpatients. Identification of underlying risk factors would be important for the development of preventive strategies.

Propensity-matched analysis of the impact of extended-spectrum ß-lactamase production on adults with community-onset Escherichia coli, Klebsiella species, and Proteus mirabilis bacteremia.

BACKGROUND: The presence of extended-spectrum ß-lactamase (ESBL) in Escherichia coli, Klebsiella species, and Proteus mirabilis (EKP) is of great microbiological and clinical importance. The study dealing with the direct impact of ESBL producers on the outcome of patients with community-onset bacteremia is lacking. METHODS: Adults with community-onset EKP bacteremia were recruited retrospectively during a 6-year period. ESBL producers were determined according to ESBL phenotype. ESBL patients were compared on a 1:2 basis with non-ESBL patients by using propensity-score matching (PSM) calculated based on independent predictors of 28-day mortality. RESULTS: Of the 1141 eligible adult patients, 65 (5.7%) caused by ESBL producers. Significant differences between the two groups were discovered in the proportions of patients with critical illness (a Pitt bacteremia score ≥ 4) at bacteremia onset, inappropriate empirical antibiotic therapy, bacteremia because of urosepsis and pneumonia, and several comorbidities. In a PSM analysis after controlling for six independent predictors-critical illness at bacteremia onset, underlying fatal comorbidities (McCabe classification), inappropriate empirical antibiotic therapy, comorbidities with liver cirrhosis, bacteremia because of urosepsis and pneumonia-a appropriate matching between two groups (ESBL group, 60 patients; non-ESBL group, 120) were observed in age, causative microorganism, bacteremia severity, major comorbidities, comorbidity severity, and major bacteremia source. Consequently, a strong relationship between ESBL producers and poor prognosis was highlighted. CONCLUSIONS: The adverse influence of ESBL producers on clinical outcomes was presented with respect to adults with community-onset EKP bacteremia. Establishing a predictive scoring algorithm for identifying patients at risk of ESBL-producer infections is crucial.

Clinical benefits of antimicrobial de-escalation in adults with community-onset monomicrobial Escherichia coli, Klebsiella species and Proteus mirabilis bacteremia.

The clinical benefits of an antimicrobial de-escalation strategy were compared with those of a no-switch strategy in bacteremic patients. Adults with community-onset monomicrobial Escherichia coli, Klebsiella species and Proteus mirabilis bacteremia treated empirically using broad-spectrum beta-lactams, including third-generation cephalosporins (GCs), fourth-GC or carbapenems, were treated definitively with first- or second-GCs (de-escalation group), the same regimens as empirical antibiotics (no-switch group), or antibiotics with a broader-spectrum than empirical antibiotics (escalation group). The eligible 454 adults were categorized as the de-escalation (231 patients, 50.9%), no-switch (177, 39.0%), and escalation (46, 10.1%) groups. Patients with de-escalation therapy were more often female, had less critical illness and fatal comorbidity, and had a higher survival rate than patients in the other two groups. After propensity score matching in the de-escalation and no-switch groups, critical illness at onset (Pitt bacteremia score ≥ 4; 16.5% vs. 12.7%; P = 0.34) or day 3 (2.5% vs. 2.5%; P = 1.00), fatal comorbidity (16.5% vs. 21.5%; P = 0.25), time to defervescence (4.6 vs. 4.7 days; P = 0.89), hospital stays (11.5 vs. 10.3 days; P = 0.13) and 4-week crude mortality rate (4.4% vs. 4.4%; P = 1.00) were similar. However, lower antibiotic cost (mean: 212.1 vs. 395.6 US$, P <0.001) and fewer complications of bloodstream infections due to resistant pathogens (0% vs. 5.1%, P = 0.004) were observed in the de-escalation group. De-escalation to narrower-spectrum cephalosporins is safe and cost-effective for adults with community-onset EKP bacteremia stabilized by empirical broad-spectrum beta-lactams.

Epidemiologic trend of adult bacterial meningitis in southern Taiwan (2006-2015).

The purpose of this study is to analyze recent epidemiologic trend of adult bacterial meningitis (ABM) in Taiwan. The clinical features, laboratory data and therapeutic outcomes of 157 patients with ABM from 2006-2015 were analyzed. The results were compared with those of our previous two epidemiologic studies of ABM (1st study: 202 cases, January 1986-June 1999; 2nd study: 181 cases, July 1999-December 2005). Of the 157 patients with ABM, 96 were men and 61 women, and 68.2% (107/157) of them had a postneurosurgical state as the underlying condition. Monomicrobial infections and mixed infections were found in 92.4% (145/157) and 7.6% (12/145) of the cases, respectively. Of the implicated pathogens of monomicrobial infections, staphylococcal species were the most common, accounting for 27.6% (40/145) of them and Klebsiella species were the second common accounting for 13.8% (20/145) of them. The other common Gram-negative pathogens were Pseudomonas species and Acinetobacter species, accounting for 10.3% (15/145) and 7.6% (11/145), respectively. The overall mortality rate was 25.5% (40/157), and septic shock and liver cirrhosis were significant prognostic factors. This study revealed a change in the epidemiologic trend of ABM and the study results may offer important information for clinicians managing patients with ABM.