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In this study, we selected bacteremic Klebsiella pneumoniae isolates from the Taiwan Surveillance of Antimicrobial Resistance program. A total of 521 isolates were collected over a period of 2 decades, including 121 from 1998, 197 from 2008, and 203 from 2018. Seroepidemiology showed that the top five capsular polysaccharide types were serotypes K1, K2, K20, K54, and K62, constituting 48.5% of the total isolates, and the respective ratios at each time point have remained similar over the past 2 decades. The antibacterial susceptibility tests showed that K1, K2, K20, and K54 were susceptible to most antibiotics, while K62 was relatively resistant compared to other typeable and nontypeable strains. In addition, six virulence-associated genes, clbA , entB , iroN , rmpA , iutA , and iucA , were predominant in K1 and K2 isolates of K. pneumoniae. In conclusion, serotypes K1, K2, K20, K54, and K62 of K. pneumoniae are the most prevalent serotypes and carry more virulence determinants in bacteremia patients, which may indicate their invasiveness. If further serotype-specific vaccine development is performed, these five serotypes should be included. Since the antibiotic susceptibility profiles were stable over a long duration, empirical treatment may be predicted according to serotype if rapid diagnosis from direct clinical specimens is available, such as PCR or antigen serotyping for serotype K1 and K2. IMPORTANCE This is the first nationwide study to examine the seroepidemiology of Klebsiella pneumoniae using blood culture isolates collected over a period of 20 years. The study found that the prevalence of serotypes remained consistent over the 20-year period, with high-prevalence serotypes associated with invasive types. Nontypeable isolates had fewer virulence determinants than other serotypes. With the exception of serotype K62, the other high-prevalence serotypes were highly susceptible to antibiotics. If rapid diagnosis using direct clinical specimens, such as PCR or antigen serotyping, is available, empirical treatment can be predicted based on serotype, particularly for K1 and K2. The results of this seroepidemiology study could also help the development of future capsule polysaccharide vaccines., Competing Interests: The authors declare no conflict of interest.

Purpose: Hypermucoviscous strains of Klebsiella pneumoniae (KP) are associated with invasive liver abscess syndrome. However, little is known about the characteristics of this phenotype in non-hepatobiliary infections. In this study, we investigated the clinical characteristics of patients with hypermucoviscous Kp (hmvKp) bacteremia from non-hepatobiliary tract infection., Methods: This retrospective cohort study was implemented at Samsung Changwon Hospital. From March 2018 to December 2019, adult patients (≥ 18 years) with KP bacteremia of the extra-hepatobiliary system were enrolled. Hypermucoviscosity was defined by the string test. Clinical characteristics and 30-day all-cause mortality between patients with hmvKp and non-hmvKp bacteremia were compared., Results: Among 179 cases of non-hepatobiliary KP bacteremia, 67 (37.4%) and 112 (62.6%) isolates were classified as hmvKp and non-hmvKp, respectively. In the hmvKp group, metastatic infection (9.0 vs. 1.8%, P = 0.054) and purulent or necrotizing infection (31.3 vs. 9.8%, P < 0.001) were more frequently observed. Additionally, non-hmvKp had more frequent resistance to cefotaxime (11.9 vs. 38.4%, P < 0.001). Thirty-day all-cause mortality was similar in the hmvKp (41.8%) and non-hmvKp (39.3%) groups (P = 0.643). In multivariable analysis, septic shock (adjusted hazard ratio [aHR] = 3.05, 95% confidence interval [CI]: 1.22-7.63) and Pitt bacteremia score (aHR = 1.23 per 1 point, 95% CI 1.14-1.33) were associated with increased mortality in patients with Kp bacteremia, while urinary-tract infection (aHR = 0.38, 95% CI 0.18-0.76) was associated with decreased mortality., Conclusion: hmvKp was associated with less frequent drug resistance and metastatic-purulent presentation in non-hepatobiliary infection like in hepatobiliary infection. However, hmvKp was not associated with clinical outcomes., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Studies comparing adult community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) and community-onset healthcare-associated MRSA (COHCA MRSA bacteremia have not been available. From 1 January 2010 through 30 October 2010, a prospective observational program was conducted among all patients aged >16 years with positive Staphylococcus aureus blood cultures within 48 h after their arrival at the emergency department of our hospital. Clinical course of infection and infection foci of bacteremia were evaluated. Resistance to oxacillin was confirmed with the presence of mecA gene examined by polymerase chain reaction. Presence of TSST-1, PVL gene, SCCmec elements (I-V), mecA gene, and multilocus sequence typing were identified through methods described elsewhere. Univariate and multivariate analysis revealed that chronic renal failure was significantly more common in COHCA-MRSA than in CA-MRSA. In addition, APACHE III score was significantly higher in COHCA-MRSA than in CA-MRSA. Both the 7-day and 30-day mortality rates in COHCA-MRSA, 14.6% (7/48) and 29.2% (14/48), respectively, were higher than those in CA-MRSA without a significant difference. SCCmec II was more common in COHCA-MRSA, but SCCmecVT was more common in CA-MRSA. The majority of MRSA isolates belonged to ST59, ST239, and ST5. ST59 was significantly more common in CA-MRSA, while ST239 was nearly equally common in both CA-MRSA and COHCA-MRSA. SCCmec III and II isolates were the first and second most resistant to the antibiotics commonly used for S. aureus, whereas SCCmecVT isolates were the most susceptible to these antibiotics. We conclude that, although both CA-MRSA and COHCA-MRSA bacteremia had community onset, these 2 MRSA infections were different in underlying diseases, risk of mortality, SCCmec types, sequence types, and antimicrobial susceptibility. It is more appropriate to understand the MRSA pathogen and clinical features based on etiology and ST types than based on the location of disease onset. CA-MRSA and HCA-MRSA should be differentiated also based on etiology and ST types, in addition to location of acquisition., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Hetero-resistant vancomycin intermediate Staphylococcus aureus (hVISA) emerges worldwide in recent decade. The purpose of this study was to investigate the glycopeptide usage trend, the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) with reduced vancomycin susceptibility, the susceptible rates to newer antimicrobials, molecular epidemiology, clinical characteristics, as well as patient outcome among S. aureus bacteremia cases in a Taiwanese medical center., Methods: From March to December 2009, among 118 S. aureus blood isolates in a Taiwanese medical center, 62 MRSA isolates were screened for hVISA by Etest macromethod and further confirmed with modified population analysis profiling method. Molecular typing of hVISA isolates was performed., Results: Five (4.2%) isolates were hVISA. Compared with non-hVISA MRSA, hVISA isolates had higher resistant rates to ciprofloxacin, gentamicin, trimethoprim/sulfamethoxazole, and tetracycline. Among the MRSA infected, patients infected with hVISA had a higher in-hospital mortality rate than non-hVISA group (60% vs. 17.5%, p = 0.025). All hVISA isolates were nosocomial and had different pulsed field gel electrophoresis pulsotype. Four hVISA isolates carried type III staphylococcal cassette chromosome mec (SCCmec) and the remaining isolate carried SCCmec type II. Three of the 5 hVISA isolates belonged to sequence type 239, which is the most common type in Taiwan. Glycopeptide usage increased in the study hospital; however, these hVISA-infected patients did not receive glycopeptide treatment in the recent 6 months., Conclusion: Our results suggested hVISA might have disseminated in the hospital before we observed this highest hVISA rate in Taiwan and increasing glycopeptide usage might serve as selection pressure. Measures to prevent the transmission of MRSA with reduced vancomycin susceptibility and to treat such infection were urgently needed., (Copyright © 2012. Published by Elsevier B.V.)

Objectives: Higher vancomycin MIC values (≥1.5 mg/L via Etest) may be associated with vancomycin treatment failure among patients with serious methicillin-resistant Staphylococcus aureus (MRSA) infections. As there were limited similar data for teicoplanin, this retrospective cohort study intended to determine the predictive value of teicoplanin MICs for treatment failure among patients with MRSA bacteraemia., Patients and Methods: All patients with at least one blood culture positive for MRSA admitted to the hospital between January 2010 and January 2011 were reviewed. Patients with an age ≥18 years and receipt of teicoplanin therapy throughout the course or receipt of <72 h of vancomycin therapy and then teicoplanin for >3 days were enrolled. Teicoplanin Etest(®) MICs and treatment outcomes for MRSA bacteraemia were reviewed to identify the breakpoint of teicoplanin MICs influencing treatment outcomes., Results: Of the 101 patients enrolled, 56 had a lower teicoplanin MIC (≤1.5 mg/L) for MRSA and 45 had a higher MIC (>1.5 mg/L) for MRSA. A lower teicoplanin MIC was associated with a favourable outcome [37 (66.1%) versus 13 (28.9%); P<0.001] and a lower rate of bloodstream infection-related mortality [15 (26.8%) versus 22 (48.9%); P=0.022]. Patients with chronic obstructive pulmonary disease, bacteraemic pneumonia or higher Pittsburgh bacteraemia score had an unfavourable outcome (P=0.028, 0.022 and <0.001, respectively). Multivariate analysis showed that teicoplanin MIC >1.5 mg/L, higher Pittsburgh bacteraemia score and bacteraemic pneumonia were independent risk factors for unfavourable outcome., Conclusions: A higher teicoplanin MIC value (>1.5 mg/L) may predict an unfavourable outcome and higher mortality rate among teicoplanin-treated MRSA bacteraemic patients.

Background and Purpose: Acinetobacter baumannii isolates containing class 1 integrons belong to different clones, but only a few strains are successful at causing infection. This study was conducted to compare the characteristics among these clones with different epidemicity., Methods: Eighty eight bacteremic isolates of A. baumannii were collected in a medical center in Taiwan during a 3-year period. The gene cassettes and antibiotic susceptibilities of the bacterial isolates were delineated and the patients' characteristics were compared., Results: Class 1 integrons were detected in 75 isolates (85.2%). Most of the isolates belonged to 2 major clones, but only 1 of the 2 clones caused outbreaks in several hospitals in Taiwan. Restriction analyses of variable regions of the integron revealed identical gene cassettes among isolates within the same clone. The cassette arrays of the 3 clones were aacA4, catB8, aadA1 (clone I, epidemic clone); dhfr XII, unknown open reading frame (orfF), aadA2 (clone II, endemic clone); and aacC1, 2 unknown open reading frames (orfX, orfX'), aadA1a (clone III). The epidemic and endemic strains were multidrug resistant, but the former presented a higher resistance rate to ampicillin-sulbactam. Infections with epidemic strains were significantly associated with prior use of cephalosporins, but didn't contribute to a higher mortality rate., Conclusions: Judicious use of cephalosporins and rapid identification using the integron typing method might be helpful for the prevention of further spread of strains with epidemic potential.

In this study, 283 multidrug-resistant Acinetobacter baumannii (MDR-AB) bloodstream isolates were collected between 1996 and 2004, from three teaching hospitals located in different regions of Taiwan. Susceptibility data showed that strains carrying class 1 integrons were significantly more resistant (p <0.01) to all tested antibiotics (except aztreonam and chloramphenicol) than strains lacking integrons, Seven types of gene cassette were identified among these strains, including two that have not been previously reported. The vast majority of the cassettes encoded aminoglycoside resistance genes, including aacA4, aacC1, aac(6')-II, aadA1, aadA2, aadA4 and aadDA1. Sixteen distinct ribotypes were identified in MDR-AB isolates carrying class 1 integrons. Only one strain was found to produce an extended-spectrum beta-lactamase, i.e. VEB-3. In the 18 imipenem-resistant strains, two carbapenenmase genes, bla(VIM-11) and bla(OXA-58), were found concomitantly in one isolate. An island-wide epidemic clone and an endemic clone from a hospital located in the northern region were identified by ribotyping. On the basis of the susceptibility data among the different ribogroups, the epidemic clone was associated more significantly with resistance to cefepime and ampicillin-sulbactam than was the endemic clone. In conclusion, the presence of class 1 integrons was significantly associated with resistance in MDR-AB, and the epidemic, class 1 integron-carrying MDR-AB clone was found to be widespread in Taiwan.

Background: Ertapenem is a once-a-day carbapenem and has excellent activity against many gram-positive and gram-negative aerobic, facultative, and anaerobic bacteria. The susceptibility of isolates of community-acquired bacteremia to ertapenem has not been reported yet. The present study assesses the in vitro activity of ertapenem against aerobic and facultative bacterial pathogens isolated from patients with community-acquired bacteremia by determining and comparing the MICs of cefepime, cefoxitin, ceftazidime, ceftriaxone, ertapenem, piperacillin, piperacillin-tazobactam, ciprofloxacin, amikacin and gentamicin. The prevalence of extended broad spectrum beta-lactamases (ESBL) producing strains of community-acquired bacteremia and their susceptibility to these antibiotics are investigated., Methods: Aerobic and facultative bacteria isolated from blood obtained from hospitalized patients with community-acquired bacteremia within 48 hours of admission between August 1, 2004 and September 30, 2004 in Chang Gung Memorial Hospital at Keelung, Taiwan, were identified using standard procedures. Antimicrobial susceptibility was evaluated by Etest according to the standard guidelines provided by the manufacturer and document M100-S16 Performance Standards of the Clinical Laboratory of Standard Institute. Antimicrobial agents including cefepime, cefoxitin, ceftazidime, ceftriaxone, ertapenem, piperacillin, piperacillin-tazobactam, ciprofloxacin, amikacin and gentamicin were used against the bacterial isolates to test their MICs as determined by Etest. For Staphylococcus aureus isolates, MICs of oxacillin were also tested by Etest to differentiate oxacillin-sensitive and oxacillin-resistant S. aureus., Results: Ertapenem was highly active in vitro against many aerobic and facultative bacterial pathogens commonly recovered from patients with community-acquired bacteremia (128/159, 80.5 %). Ertapenem had more potent activity than ceftriaxone, piperacillin-tazobactam, or ciprofloxacin against oxacillin-susceptible S. aureus (17/17, 100%)and was more active than any of these agents against enterobacteriaceae (82/82, 100%)., Conclusion: Based on the microbiology pattern of community-acquired bacteremia, initial empiric treatment that requires coverage of a broad spectrum of both gram-negative and gram-positive aerobic bacteria, such as ertapenem, may be justified in moderately severe cases of community-acquired bacteremia in non-immunocompromised hosts.

Twenty-seven isolates of vancomycin-resistant enterococci were obtained at monthly intervals from a bed-ridden man with hypoxic encephalopathy. During the 28-month period of the patient's hospitalization, 3 episodes of bacteremia and one episode of catheter-related infection caused by vancomycin-resistant enterococci occurred. Rectal swabs showed colonization of vancomycin-resistant enterococci for more than 2 years. Three months after termination of antimicrobial therapy, the rectal colonization for vancomycin-resistant enterococci was eradicated. Four species (Enterococcus faecium, Enterococcus gallinarum, Enterococcus faecalis, and Enterococcus casseliflavus) were identified among the 27 vancomycin-resistant enterococcus isolates. Three non-clonal related patterns were found among 17 strains of E. faecium by pulsed-field gel electrophoresis. All of the 3 E. faecalis isolates were of the VanB phenotype, but of the vanA genotype. Linezolid had the most potent in vitro activity against these vancomycin-resistant enterococcus isolates, with minimum inhibitory concentrations >2 microg/mL. Eighty-five percent of these vancomycin-resistant enterococcus isolates were susceptible to tetracycline and 66% were susceptible to quinupristin-dalfopristin. Although a high genetic correlation of E. faecium was identified in the patient with prolonged hospitalization, the isolation of 3 genetically unrelated colonized isolates suggested a lack of correlation between infection and colonization. Precautions against resistant organisms, adapted antibiotic policies, and elimination of patient carriage are useful for controlling the spread of vancomycin-resistant enterococci.

Background: Although several epidemiological surveys of Klebsiella clinical isolates have been performed, few studies have correlated the clinical isolate with disease., Objective: To compare the clinical and bacteriological characteristics of Klebsiella pneumoniae bacteremia acquired as community or nosocomial infections., Methods: We prospectively enrolled 158 consecutively hospitalized patients with K pneumoniae bacteremia. Clinical data were reviewed. Antimicrobial susceptibility testing and capsular serotyping were performed. We used the chi(2) test, the Fisher exact test, or the t test for statistic analysis., Results: Underlying diabetes mellitus was more common in community-acquired than in nosocomial infection (46/94 [49%] vs. 8/64 [12%]; P<.001). On the other hand, neoplastic disease (34/64 [53%] vs. 13/94 [14%]; P<.001) and antibiotic resistance (P<.01) were more frequent in patients with nosocomial compared with community-acquired infections. Klebsiella pneumoniae liver abscesses, which were all community acquired, accounted for the source of 22 (23%) of 94 community-acquired K pneumoniae infections. No attributable source of infection was found for 37 (58%) of the 64 nosocomial infections vs. 15 (16%) of the 94 community-acquired infections. Only 58 isolates (36.7%) could be serotyped; of these, capsular serotypes K1, K2, and K28 accounted for 37 (23.4%), 8 (5.1%), and 6 (3.8%), respectively, of all strains. However, typeable isolates were significantly more common among community-acquired than nosocomial isolates (42/94 [45%] vs. 16/64 [25%]; P =.01), especially for serotype K1 (28/94 [30%] vs. 9/64 [14%]; P =.02). Significant risk factors for mortality included nosocomial infection, lung infection, thrombocytopenia, leukopenia, ceftazidime resistance, inappropriate antimicrobial therapy, and septic shock., Conclusions: Significant differences were identified between community-acquired and nosocomial K pneumoniae bacteremia. Ceftazidime resistance in nosocomial K pneumoniae bacteremia carried a high risk for mortality, and serotype K1 in K pneumoniae was more prevalent in community-acquired infection, suggesting more virulence.

Thirteen patients who had 16 episodes of bacteremia were observed between 1993 and 1997 in a pediatric oncology ward with a high background isolation rate of cefotaxime- or aztreonam-resistant gram-negative bacteria. Four blood isolates were Escherichia coli and 12 were Klebsiella pneumoniae, and these isolates harbored extended-spectrum beta-lactamases (ESBLs). All episodes of bacteremia were nosocomial, all except one of the episodes occurred in neutropenic patients, and all patients were treated with piperacillin or ceftazidime with amikacin and cefazolin prior to the onset of bacteremia. Nine of 13 patients were receiving extended-spectrum beta-lactam treatment when the bacteremias caused by ESBL producers occurred. Molecular studies revealed that four K. pneumoniae SHV-2-producing isolates from 1994 were of the same clone. Other ESBL producers, including six that carried both TEM-1 and SHV-5, five that carried SHV-5, and one that carried SHV-2 alone, were unrelated. In conclusion, SHV-5 was present in 11 of the 16 isolates and coexisted with TEM-1 in 6 isolates. Acquisition of resistance genes probably occurred under antibiotic selection pressure. This study highlights the importance of routine checks for and detection of ESBL producers. Effective therapy against ESBL producers should be considered early for children who have malignancies and neutropenia and who are septic, despite treatment with a regimen that includes an extended-spectrum beta-lactam, in a clinical setting of an increased incidence of ESBL-producing bacteria.

Background: Klebsiella variicola and K. quasipneumoniae are new species distinguishable from K. pneumoniae but they are often misidentified as K. pneumoniae in clinical settings. Several reports have demonstrated the possibility that the virulence factors and clinical features differ among these three phylogroups. In this study, we aimed to clarify whether there were differences in clinical and bacterial features between the three phylogroups isolated from patients with bloodstream infections (BSIs) in Japan., Methods: Isolates from all patients with BSIs caused by K. pneumoniae admitted to two hospitals between 2014 and 2017 (n = 119) were included in the study. Bacterial species were identified via sequence analysis, and their virulence factors and serotypes were analyzed via multiplex PCR results. Clinical data were retrieved from medical records., Results: Of the 119 isolates, 21 (17.7%) were identified as K. variicola and 11 (9.2%) as K. quasipneumoniae; K1 serotype was found in 16 (13.4%), and K2 serotype in 13 (10.9%). Significant differences in the prevalence of rmpA, iutA, ybtS, entB and kfu (p < 0.001), and allS genes (p < 0.05) were found between the three phylogroups. However, there were no significant differences in clinical features, including the 30-day mortality rate, between the three organisms, although K. variicola was more frequently detected in patients over 80 years old compared with other Klebsiella species (p < 0.005), and K. quasipneumoniae more frequently occurred in patients with malignancy (p < 0.05)., Conclusions: Our findings demonstrated the differences in bacterial pathogenicity and clinical features among these three phylogroups. Further epidemiological studies into BSI caused by Klebsiella species are warranted.

INTRODUCTION: Klebsiella pneumonia (K. pneumonia) bacteremia is one of the leading causes of hospital morbidity and mortality. Our study aimed to evaluate the clinical characteristics, risk factors and outcomes of K. pneumonia bacteremia in a Malaysian public hospital. MATERIALS AND METHODS: A retrospective cross-sectional study of adults with K. pneumonia bacteremia was conducted in a hospital in Johor, Malaysia. Demographics, medical comorbidities, source of infections and the mortality rate was reviewed and analyzed. RESULTS: A total of 185 cases of K. pneumonia bacteremia were included for analysis. The mean age for this study was 54.9 (SD 15.4), with 56.8% males and 46.5% in-hospital mortality. Extended-spectrum Beta Lactamase (ESBL) producing and Carbapenem-resistant K. pneumonia contributed to 37.3% and 1.1% of K. pneumonia bacteremia, respectively. Among those who contracted K. pneumonia bacteremia, three most frequent sources were primary bloodstream infections (n=75, 40.5%), pneumonia (n=44, 23.8%) and urinary tract infections (n=28, 15.1%) "or" the most frequent sources were primary bloodstream infections (n=75, 40.5%), pneumonia (n=44, 23.8%) and urinary tract infections (n=28, 15.1%). There was statistically significant associations found between diabetes mellitus (AOR 1.46, 95% CI 1.02-2.08), cancer (AOR 2.02, 95% CI 1.33-3.05) and alcohol use disorder (AOR 7.73,95% CI 1.38-43.21) with K. pneumonia bacteremia. In-hospital mortality was higher in older patients by 1.03 odds (p=0.003). CONCLUSION: Diabetes mellitus, cancer, and alcohol use disorder were independent risk factors associated with K. pneumonia bacteremia. Patients with advanced age had a higher mortality rate. [ABSTRACT FROM AUTHOR]

Background and objectives: Klebsiella pneumoniae (K. pneumoniae) is the second leading cause of community-acquired and hospital-acquired gram-negative bloodstream infection (BSI). This study aimed to assess the epidemiological and microbial-resistance characteristics and clinical factors associated with K. pneumoniae BSI in Saudi Arabia. Materials and Methods: Data of 152 K. pneumoniae isolates diagnosed between January 2019 and January 2020 at King Fahad Medical City, Riyadh, Saudi Arabia were evaluated retrospectively. Clinical records of the patients were collected and analysed statistically. Results: In total, 152 cases of K. pneumoniae BSI were identified. Adult patients (66.4%) were at a higher risk of developing the infection than paediatric patients (33.6%). The rate of infection was slightly higher in women than in men. Neurological disorders were the predominant underlying conditions for the acquisition of K. pneumoniae BSI, at all ages. Most of the deceased patients were adults with multi-organ dysfunction. Klebsiella pneumoniae showed disturbing resistance to amoxicillin-clavulanate and cefuroxime (72.4%), ceftazidime (67.8), cephalothin (76.3%), and to Carbapenems (36.1%). Conclusions: The impact of K. pneumoniae BSI was seen not only at the patient level, but also at the community level, and was related to multi-drug resistant infection. These findings provide a better understanding of microbial resistance and its association with patient clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: Klebsiella pneumoniae strains have been divided into two major categories: classical K. pneumoniae, which are frequently multidrug-resistant and cause hospital-acquired infections in patients with impaired defenses, and hypervirulent K. pneumoniae, which cause severe community-acquired and disseminated infections in normal hosts. Both types of infections may lead to bacteremia and are associated with significant morbidity and mortality. The relative burden of these two types of K. pneumoniae among bloodstream isolates within the United States is not well understood.Methods: We evaluated consecutive K. pneumoniae isolates cultured from the blood of hospitalized patients at Northwestern Memorial Hospital (NMH) in Chicago, Illinois between April 2015 and April 2017. Bloodstream isolates underwent whole genome sequencing, and sequence types (STs), capsule loci (KLs), virulence genes, and antimicrobial resistance genes were identified in the genomes using the bioinformatic tools Kleborate and Kaptive. Patient demographic, comorbidity, and infection information, as well as the phenotypic antimicrobial resistance of the isolates were extracted from the electronic health record. Candidate hypervirulent isolates were tested in a murine model of pneumonia, and their plasmids were characterized using long-read sequencing. We also extracted STs, KLs, and virulence and antimicrobial resistance genes from the genomes of bloodstream isolates submitted from 33 United States institutions between 2007 and 2021 to the National Center for Biotechnology Information (NCBI) database.Results: Consecutive K. pneumoniae bloodstream isolates (n = 104, one per patient) from NMH consisted of 75 distinct STs and 51 unique capsule loci. The majority of these isolates (n = 58, 55.8%) were susceptible to all tested antibiotics except ampicillin, but 17 (16.3%) were multidrug-resistant. A total of 32 (30.8%) of these isolates were STs of known high-risk clones, including ST258 and ST45. In particular, 18 (17.3%) were resistant to ceftriaxone (of which 17 harbored extended-spectrum beta-lactamase genes) and 9 (8.7%) were resistant to meropenem (all of which harbored a carbapenemase genes). Four (3.8%) of the 104 isolates were hypervirulent K. pneumoniae, as evidenced by hypermucoviscous phenotypes, high levels of virulence in a murine model of pneumonia, and the presence of large plasmids similar to characterized hypervirulence plasmids. These isolates were cultured from patients who had not recently traveled to Asia. Two of these hypervirulent isolates belonged to the well characterized ST23 lineage and one to the re-emerging ST66 lineage. Of particular concern, two of these isolates contained plasmids with tra conjugation loci suggesting the potential for transmission. We also analyzed 963 publicly available genomes of K. pneumoniae bloodstream isolates from locations within the United States. Of these, 465 (48.3%) and 760 (78.9%) contained extended-spectrum beta-lactamase genes or carbapenemase genes, respectively, suggesting a bias towards submission of antibiotic-resistant isolates. The known multidrug-resistant high-risk clones ST258 and ST307 were the predominant sequence types. A total of 32 (3.3%) of these isolates contained aerobactin biosynthesis genes and 26 (2.7%) contained at least two genetic features of hvKP strains, suggesting elevated levels of virulence. We identified 6 (0.6%) isolates that were STs associated with hvKP: ST23 (n = 4), ST380 (n = 1), and ST65 (n = 1).Conclusions: Examination of consecutive isolates from a single center demonstrated that multidrug-resistant high-risk clones are indeed common, but a small number of hypervirulent K. pneumoniae isolates were also observed in patients with no recent travel history to Asia, suggesting that these isolates are undergoing community spread in the United States. A larger collection of publicly available bloodstream isolate genomes also suggested that hypervirulent K. pneumoniae strains are present but rare in the USA; however, this collection appears to be heavily biased towards highly antibiotic-resistant isolates (and correspondingly away from hypervirulent isolates). [ABSTRACT FROM AUTHOR]

Background: Escherichia coli (E. coli) is a common human pathogen, responsible for a broad spectrum of infections. Sites of infection can vary, but the hepato-biliary system is of particular concern due to the infection-associated formation of gallstones and the spread of pathogens from the bile ducts into the bloodstream. Case presentation: The presented case is striking, as the detected isolate showed a positive string test. This hypermucoviscous phenotype is atypical for E. coli and a particular feature of hypervirulent Klebsiella pneumoniae (K. pneumoniae) variants. Objectives: To provide new insights into the genomic background of an E. coli strain with an unusual hypermucoviscous phenotype using hybrid short- and long-read sequencing approaches. Results: Complete hybrid assemblies of the E. coli genome and plasmids were done and used for genome based typing. Isolate 537–20 was assigned to the multilocus sequence type ST88 and serotype O8:H4. The strain showed a close relationship to avian pathogenic strains. Analysis of the chromosome and plasmids revealed the presence of several virulence factors, such as the Conserved Virulence Plasmidic (CVP) region on plasmid 537-20_1, including several iron acquisition genes (sitABCD, iroABCDEN, iucABCD, hbd) and the iutA gene encoding the receptor of the siderophore aerobactin. The hypermucoviscous phenotype could be caused by encapsulation of putative K. pneumoniae origin. Conclusions: Hybrid sequencing enabled detailed genomic characterization of the hypermucoviscous E. coli strain, revealing virulence factors that have their putative origin in K. pneumoniae. [ABSTRACT FROM AUTHOR]

Purpose: Clinical patterns of Klebsiella pneumoniae bacteraemia vary geographically. An invasive syndrome involving abscess formation has emerged in recent years. Putative virulence factors associated with this syndrome include colony hypermucoviscosity, and magA and rmpA genes. We studied epidemiologic and microbiologic characteristics of K. pneumoniae bacteraemia at two South Australian hospitals and identified cases of K. pneumoniae invasive syndrome. We determined the frequency of the hypermucoviscosity, magA and rmpA genes among bacteraemic and selected non-bacteraemic isolates. Methods: Thirty-one patients with K. pneumoniae bacteraemia treated between June 2010 and July 2011 were included. Existing records were examined for relevant clinical and microbiological data. Urinary and wound isolates were also examined. Hypermucoviscosity was identified by a positive string test, whilst polymerase chain reaction detected magA and rmpA positive isolates. Results: Of 31 blood culture isolates, 22 were associated with community-acquired infection. Biliary infection was the commonest source, occurring in ten patients. Three patients had K. pneumoniae invasive syndrome, all of Asian extraction ( p = 0.0044). Four blood isolates demonstrated one or more of hypermucoviscosity, magA or rmpA; three were from patients with liver abscesses. Liver abscess isolates were all K1 serotype and had similar PFGE profiles. Conclusions: This study augments understanding of local epidemiology and microbiology of K. pneumoniae bacteraemia. It confirms local emergence of K. pneumoniae invasive syndrome and implicates the role of magA and rmpA genes in its pathogenesis. [ABSTRACT FROM AUTHOR]

Background: Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacterales bacteremia is associated with significant mortality; however, no optimal antibiotic strategy is available. We aimed to evaluate the clinical outcomes according to the antibiotic regimens and identify risk factors for mortality in patients with KPC-producing K. pneumoniae and Escherichia coli bacteremia. Materials and Methods: This retrospective cohort study included all adult patients with monomicrobial bacteremia (KPC-producing K. pneumoniae or E. coli) between January 2011 and March 2021 at a 2,700-bed tertiary center. Results: Ninety-two patients were identified; 7 with E. coli bacteremia, and 85 with K. pneumoniae bacteremia. Thirty-day mortality was 38.0% (35/92). Non-survivors were more likely to have had nosocomial infection (88.6% vs. 63.2%, P = 0.01), high APACHE II scores (mean [interquartile range], 22.0 [14.0 - 28.0] vs. 14.0 [11.0 - 20.5], P <0.001), and septic shock (51.4% vs. 26.3%, P <0.001) and less likely to have been admitted to the surgical ward (5.7% vs. 22.8%, P = 0.04), undergone removal of eradicable foci (61.5% vs. 90.6%, P = 0.03), and received appropriate combination treatment (57.1% vs. 78.9%, P = 0.03) than survivors. No significant difference in mortality was observed according to combination regimens including colistin, aminoglycoside, and tigecycline. In multivariable analysis, high APACHE II scores (adjusted odds ratio [aOR], 1.14; 95% confidence interval [CI], 1.06 - 1.23, P <0.001), and appropriate definitive treatment (aOR, 0.25; CI, 0.08 - 0.74, P = 0.01) were independent risk factors for mortality. Conclusion: High APACHE II scores and not receiving appropriate definitive treatment were associated with 30-day mortality. Mortality did not significantly differ according to combination regimens with conventional drugs such as aminoglycoside and colistin. [ABSTRACT FROM AUTHOR]

Background: Bloodstream infection is a life-threatening clinical condition posing significant morbidities and mortalities. An "Emergency Critical Care Management Program" has been implemented in the Emergency Medicine Ward at North Lantau Hospital as a pilot critical care service model in the local emergency medicine wards. Patients with blood stream infection are recruited in the program and managed under pre-defined guideline. Objectives: We report our experience in managing patients with blood stream infection in the Emergency Medicine Ward and analyzed their clinical outcomes. Methods: This was a retrospective cohort study including a total of 64 patients with blood stream infection admitted to the Emergency Medicine Ward from 1 March 2015 and 31 March 2018. Patients' characteristics, microbiology, and risk factors associated with adverse outcomes including in-hospital mortality were analyzed. Results: The most common organism isolated from blood cultures was Escherichia coli (56%). Eight patients were transferred to the tertiary hospital. The overall in-hospital mortality was 7.8% (5/64). From the univariate analysis, advanced age (p < 0.001), higher Sequential Organ Failure Assessment score and quick Sequential Organ Failure Assessment score (p < 0.001), higher Charlson Comorbidity Index (p = 0.003), more organ dysfunction (p < 0.001), pre-existing medical history of chronic liver disease (p = 0.001), dysfunction in respiratory system (p = 0.032), cardiovascular system (p = 0.044) and the central nervous system (p < 0.001), presence of septic shock (p = 0.004), and need for higher level of organ support from the use of inotropes (p < 0.001) and mechanical ventilation (p = 0.024) were associated with in-hospital mortality. In the subgroup analysis, the in-hospital mortality rate for the patients with Sequential Organ Failure Assessment score less than 6 was 1.56% (1/64). Among the five in-hospital mortality cases, four of them were managed in the Emergency Medicine Ward under the End-of-Life Care Program. Decision for withholding and withdrawing life-sustaining therapy was made with the patients' families. Conclusion: This preliminary report demonstrated that with careful patient selection, adoption of guidelines, and availability of expertise, critical care service can be safely implemented in the emergency medicine ward. [ABSTRACT FROM AUTHOR]

Background: Klebsiella spp. are important pathogens associated with bacteremia among admitted children and is among the leading cause of death in children < 5 years in postmortem studies, supporting a larger role than previously considered in childhood mortality. Herein, we compared the antimicrobial susceptibility, mechanisms of resistance, and the virulence profile of Klebsiella spp. from admitted and postmortem children.Methods: Antimicrobial susceptibility and virulence factors of Klebsiella spp. recovered from blood samples collected upon admission to the hospital (n = 88) and postmortem blood (n = 23) from children < 5 years were assessed by disk diffusion and multiplex PCR.Results: Klebsiella isolates from postmortem blood were likely to be ceftriaxone resistant (69.6%, 16/23 vs. 48.9%, 43/88, p = 0.045) or extended-spectrum β-lactamase (ESBL) producers (60.9%, 14/23 vs. 25%, 22/88, p = 0.001) compared to those from admitted children. blaCTX-M-15 was the most frequent ESBL gene: 65.3%, 9/14 in postmortem isolates and 22.7% (5/22) from admitted children. We found higher frequency of genes associated with hypermucoviscosity phenotype and invasin in postmortem isolates than those from admitted children: rmpA (30.4%; 7/23 vs. 9.1%, 8/88, p = 0.011), wzi-K1 (34.7%; 8/23 vs. 8%; 7/88, p = 0.002) and traT (60.8%; 14/23 vs. 10.2%; 9/88, p < 0.0001), respectively. Additionally, serine protease auto-transporters of Enterobacteriaceae were detected from 1.8% (pic) to 12.6% (pet) among all isolates. Klebsiella case fatality rate was 30.7% (23/75).Conclusion: Multidrug resistant Klebsiella spp. harboring genes associated with hypermucoviscosity phenotype has emerged in Mozambique causing invasive fatal disease in children; highlighting the urgent need for prompt diagnosis, appropriate treatment and effective preventive measures for infection control. [ABSTRACT FROM AUTHOR]

Background: Many studies have shown that vancomycin is inferior to β-lactam antibiotics in terms of effectiveness in the treatment of methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. However, limited data are available regarding the comparison of clinical outcomes between patients receiving initial teicoplanin and those receiving β-lactam antibiotics for MSSA bacteremia.Methods: Eighty-four adults with MSSA bacteremia were included: initial teicoplanin treatment group (n = 28) and β-lactam treatment group (n = 56). The two groups were further stratified based on propensity score matching according to the outcome analysis using a logistic regression model. We investigated the clinical outcomes between the groups before and after propensity score matching after treatment completion.Results: Pittsburgh bacteremia score ≥ 4 (odds ratio, 60.6; 95%CI, 7.4-496.8) was an independent risk factor for unfavorable outcome. After propensity score matching, the initial teicoplanin treatment group and the β-lactam treatment group consisted of 28 patients each. No statistically significant differences were observed in the proportions of patients with favorable outcomes and 30-day overall mortality rates between the groups before and after propensity score matching after the completion of teicoplanin or β-lactam treatment. The Kaplan-Meier 30-day survival curve also showed no significant difference between the patients receiving initial teicoplanin treatment and those receiving β-lactam treatment before and after matching (hazard ratio, 1.84, 95%CI, 0.60-5.64; and 3.12, 95%CI, 0.98-9.99, respectively).Conclusions: There were no significant difference in clinical outcomes between initial teicoplanin treatment and β-lactam treatment among patients with MSSA bacteremia. Pittsburgh bacteremia score ≥ 4 was a significant risk factor for mortality. [ABSTRACT FROM AUTHOR]

Adequate empirical antimicrobial coverage is instrumental in clinical management of community-onset Enterobacteriaceae bacteraemia in areas with high ESBL prevalence, while balancing the risk of carbapenem overuse and emergence of carbapenem-resistant organisms. It is unknown whether machine learning offers additional advantages to conventional statistical methods in prediction of ESBL production. To develop a validated model to predict ESBL production in Enterobacteriaceae causing community-onset bacteraemia. 5625 patients with community-onset bacteraemia caused by Escherichia coli, Klebsiella species and Proteus mirabilis during 1 January 2015–31 December 2019 from three regional hospitals in Hong Kong were included in the analysis, after exclusion of blood cultures obtained beyond 48 h of admission. The prevalence of ESBL-producing Enterobacteriaceae was 23.7% (1335/5625). Deep neural network and other machine learning algorithms were compared against conventional statistical model via multivariable logistic regression. Primary outcomes compared consisted of predictive model area under curve of receiver-operator characteristic curve (AUC), and macro-averaged F1 score. Secondary outcomes included sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Deep neural network yielded an AUC of 0.761 (95% CI 0.725–0.797) and F1 score of 0.661 (95% CI 0.633–0.689), which was superior to logistic regression (AUC 0.667 (95% CI 0.627–0.707), F1 score 0.596 (95% CI 0.567–0.625)). Deep neural network had a specificity of 91.5%, sensitivity of 37.5%, NPV of 82.5%, and PPV of 57.9%. Deep neural network is superior to logistic regression in predicting ESBL production in Enterobacteriaceae causing community-onset bacteraemia in high-ESBL prevalence area. Machine learning offers clinical utility in guiding judicious empirical antibiotics use. [ABSTRACT FROM AUTHOR]

Background: Ceftriaxone is the preferred treatment for bacteraemia caused by non-MDR (antibiotic-susceptible) Klebsiella pneumoniae. Excessive and widespread ceftriaxone use creates selection pressure for ESBLs. Cefazolin is an alternative, although there are theoretical concerns that SHV-1 β-lactamase in K. pneumoniae may inactivate cefazolin in an inoculum-dependent manner.Objectives: In this retrospective study, we investigated the outcomes in K. pneumoniae bacteraemia patients treated with IV cefazolin versus IV ceftriaxone as definitive therapy.Methods: A total of 917 patients infected with K. pneumoniae from 1 January to 31 December 2016 in three public acute care hospitals in Singapore were screened for study eligibility. Consecutive unique episodes of monomicrobial bacteraemia caused by cefazolin- and/or ceftriaxone-susceptible K. pneumoniae were analysed (n = 284).Results: There were 143 patients (50.4%) in the cefazolin group and 141 patients (49.6%) in the ceftriaxone group. Demographics, baseline illness severity and risk factors for healthcare-associated bacteraemia were comparable in the two treatment groups. The primary outcome of 28 day all-cause mortality was not significantly different between the cefazolin and ceftriaxone groups (10.5% versus 7.1%, P = 0.403). Both in the crude analysis and using a multivariable logistic regression model with inverse probability weighting based on propensity score, cefazolin treatment was not associated with increased risk of 28 day mortality (OR 1.51 with ceftriaxone as the reference group, 95% CI 0.67-3.53; adjusted OR 1.55, 95% CI 0.33-7.40).Conclusions: Cefazolin may be a ceftriaxone-sparing alternative treatment for antibiotic-susceptible K. pneumoniae bacteraemia. This observation may provide sufficient clinical equipoise for a randomized controlled trial. [ABSTRACT FROM AUTHOR]

Purpose: Klebsiella pneumoniae-induced liver abscess and baiacterem is a serious infectious disease with high mortality. Secondary bile acids (SBAs) are produced by intestinal flora through the metabolism of primary bile acids and play a role in promoting or inhibiting inflammation in some diseases. However, the immunomodulatory role of SBAs in bacterial infections of the liver remains unclear. This study aimed to investigate the anti-inflammatory and liver-protective effects of SBAs in K. pneumoniae-infected mice. Methods: The absolute concentrations of deoxycholic acid (DCA) and lithocholic acid (LCA) in feces and serum were analyzed, and intestinal flora alterations between K. pneumoniae-infected and healthy control mice were examined. The effect of SBAs was investigated by analyzing the survival, tissue bacterial load, histopathology, and inflammatory factor levels in SBA-treated mice. The expression of crucial proteins implicated in the NF-κB pathway, as well as the G-protein-coupled bile acid receptor TGR5, was detected. Results: The content of SBAs in feces and serum of the K. pneumoniae-infected group was significantly reduced, and significant changes in the composition of the intestinal flora were detected. The intestinal flora are directly related to the synthesis of SBAs. Ruminococcaceae levels in K. pneumoniae-infected mice were significantly lower than in healthy control mice. Oral administration of SBAs improved the survival and liver pathology of K. pneumoniae-infected mice, and reduced the bacterial load and the level of inflammatory factors. SBAs down-regulated the expression of key proteins in the NF-κB inflammatory signaling pathway, including the phosphorylation of IκBα and NF-κB p50 and the nuclear translocation of NF-κB p65. The protective effect of SBAs may be dependent on high TGR5 expression. Conclusion: SBAs downregulate the NF-κB inflammatory signaling pathway through TGR5, protecting the liver and inhibiting inflammation in K. pneumoniae-induced liver abscess and bacteremia. [ABSTRACT FROM AUTHOR]

Background: Approximately half of clinical carbapenem-resistant Enterobacterales (CRE) isolates lack carbapenem-hydrolysing enzymes and develop carbapenem resistance through alternative mechanisms.Objectives: To elucidate development of carbapenem resistance mechanisms from clonal, recurrent ESBL-positive Enterobacterales (ESBL-E) bacteraemia isolates in a vulnerable patient population.Methods: This study investigated a cohort of ESBL-E bacteraemia cases in Houston, TX, USA. Oxford Nanopore Technologies long-read and Illumina short-read sequencing data were used for comparative genomic analysis. Serial passaging experiments were performed on a set of clinical ST131 Escherichia coli isolates to recapitulate in vivo observations. Quantitative PCR (qPCR) and qRT-PCR were used to determine copy number and transcript levels of β-lactamase genes, respectively.Results: Non-carbapenemase-producing CRE (non-CP-CRE) clinical isolates emerged from an ESBL-E background through a concurrence of primarily IS26-mediated amplifications of blaOXA-1 and blaCTX-M-1 group genes coupled with porin inactivation. The discrete, modular translocatable units (TUs) that carried and amplified β-lactamase genes mobilized intracellularly from a chromosomal, IS26-bound transposon and inserted within porin genes, thereby increasing β-lactamase gene copy number and inactivating porins concurrently. The carbapenem resistance phenotype and TU-mediated β-lactamase gene amplification were recapitulated by passaging a clinical ESBL-E isolate in the presence of ertapenem. Clinical non-CP-CRE isolates had stable carbapenem resistance phenotypes in the absence of ertapenem exposure.Conclusions: These data demonstrate IS26-mediated mechanisms underlying β-lactamase gene amplification with concurrent outer membrane porin disruption driving emergence of clinical non-CP-CRE. Furthermore, these amplifications were stable in the absence of antimicrobial pressure. Long-read sequencing can be utilized to identify unique mobile genetic element mechanisms that drive antimicrobial resistance. [ABSTRACT FROM AUTHOR]

Introduction: Infections caused by Extensively Drug-resistant Pseudomonas aeruginosa (XDR-PA) is a medical problem worldwide. In Thailand, the incidence of XDR-PA bacteremia remains and is continuously increasing. Aim: To investigate an association between antimicrobial agent administration and the treatment of XDR-PA infection among patients admitted in Intensive Care Unit (ICU). Materials and Methods: A hospital-based analytic crosssectional study was performed from January 2014 to December 2015. Of these, 47 cases diagnosed with XDR-PA bacteremia infection and 94 controls without XDR-PA infection were enrolled. Data were retrieved and retrospectively reviewed from medical records of the patients hospitalised in the ICU at Roi-Et Hospital, Thailand. Multiple logistic regressions were used and perform to investigate an association between antimicrobial agent administrations for treatment of XDR-PA infection. Results: Third generation Cephalosporin (OR=1.99; 95%CI: 1.22 to 4.13), Ciprofloxacin (OR=3.40; 95%CI: 1.24 to 9.49) and Carbapenem (OR=4.66; 95%CI: 2.04 to 10.64) were more likely to be administrated for treatment of XDR-PA infection among patients. Conclusion: Antimicrobial agents associated with the treatment of XDR-PA bacteremia infection among patients were third generation Cephalosporin, Ciprofloxacin and Carbapenem. [ABSTRACT FROM AUTHOR]

Introduction: Klebsiella pneumoniae is a pathogen commonly found in community-onset bacteremia. It causes an invasive syndrome that is frequently presented by metastatic infections and abscesses elsewhere and that is necessary for surgical or drainage intervention. To achieve a scoring algorithm to identify patients with community-onset K. pneumoniae bacteremia (CoKPB) who are at risk for abscess occurrences, a retrospective cohort study consisting of adults with CoKPB was conducted. Methods: A 6-year cohort study consisting of adults having community-onset monomicrobial K. pneumoniae bacteremia was conducted. In addition to clinical variables collected from medical records, the hypermucoviscosity (HMV)-related gene (rmpA and magA) and an HMV phenotype were integrated into the proposed scoring algorithm. Results: Of the 258 eligible adults, only 79 (30.6%) had abscesses related to bacteremia. Besides the presence of magA (ie, capsular serotype K1) and the HMV-phenotype, five clinical predictors were significantly associated with abscesses in a multivariate analysis: male gender, comorbidities with diabetes mellitus or neurological disorders, recent chemotherapy, and high c-reactive protein levels. Together, these predictors were used to calculate the CoKPB abscess score. Based on the scoring algorithm, a cut-off value of +2 yielded the high sensitivity (93.7%) and the acceptable specificity (50.8%); the area under the ROC curve was 0.83. Conclusion: A simple scoring algorithm that has substantial sensitivity and satisfactory specificity was proposed and the importance of the HMV phenotype or capsular K1 serotype was emphasized. The proposed predictive model needs external validation, but this scoring algorithm might be convenient and useful for clinicians. [ABSTRACT FROM AUTHOR]

Background: Klebsiella species are among the most common causes of bloodstream infection (BSI). However, few studies have evaluated their epidemiology in non-selected populations. The objective was to define the incidence of, risk factors for, and outcomes from Klebsiella species BSI among residents of the western interior of British Columbia, Canada.Methods: Population-based surveillance was conducted between April 1, 2010 and March 31, 2017.Results: 151 episodes were identified for an incidence of 12.1 per 100,000 population per year; the incidences of K. pneumoniae and K. oxytoca were 9.1 and 2.9 per 100,000 per year, respectively. Overall 24 (16%) were hospital-onset, 90 (60%) were healthcare-associated, and 37 (25%) were community-associated. The median patient age was 71.4 (interquartile range, 58.8-80.9) years and 88 (58%) cases were males. Episodes were uncommon among patients aged < 40 years old and no cases were observed among those aged < 10 years. A number of co-morbid medical illnesses were identified as significant risks and included (incidence rate ratio; 95% confidence interval) cerebrovascular accident (5.9; 3.3-9.9), renal disease 4.3; 2.5-7.0), cancer (3.8; 2.6-5.5), congestive heart failure (3.5; 1.6-6.6), dementia (2.9; 1.5-5.2), diabetes mellitus (2.6; 1.7-3.9), and chronic obstructive pulmonary disease (2.3; 1.5-3.5). Of the 141 (93%) patients admitted to hospital, the median hospital length stay was 8 days (interquartile range, 4-17). The in-hospital and 30-day all cause case-fatality rates were 24/141 (17%) and 27/151 (18%), respectively.Conclusions: Klebsiella species BSI is associated with a significant burden of illness particularly among those with chronic co-morbid illnesses. [ABSTRACT FROM AUTHOR]

Adjustment for confounding is important in observational methicillin-resistant Staphylococcus aureus bacteremia (MRSAB) studies due to the wide spectrum of disease severity and baseline health status that patients present with. The objectives of this study were to develop a simplified MRSAB-specific scoring model to estimate the risk of 30-day all-cause mortality and to compare its performance to the APACHE II and Pitt Bacteremia scores. Retrospective, singe-center, cohort study in adults with MRSAB 2008 to 2018. Independent predictors of mortality were identified through multivariable logistic regression. A scoring model was derived using a regression coefficient-based scoring method. Discriminatory ability was assessed using the c statistic. A total of 455 patients were included. Thirty-day mortality was 16.3%. The MRSAB score consisted of six variables: age, respiratory rate, Glasgow Coma scale, renal failure, hospital-acquired MRSAB, and infective endocarditis or lower respiratory tract infection source. The score demonstrated very good discrimination (c statistic 0.8662, 95% CI 0.824–0.909) and was superior to the APACHE II (P = 0.043) and the Pitt bacteremia (P < 0.001) scores. A weighted combination of six independent variables routinely measured in patients with MRSAB can be used to predict, with high discrimination, 30-day all-cause mortality. External validation is required before widespread use. [ABSTRACT FROM AUTHOR]

Background Klebsiella pneumoniae carbapenemase (KPC)–producing K. pneumoniae (KPC-Kp) has emerged globally over the last decade as a major nosocomial pathogen that threatens patient care. These highly resistant bacteria are mostly associated with a single Kp clonal group, CG258, but the reasons for its host and hospital adaptation remain largely unknown. Methods We analyzed the in vivo evolution of a colistin-resistant KPC-Kp CG258 strain that contaminated a patient following an endoscopy and was responsible for a fatal bacteremia 4.5 years later. Whole-genome sequencing was performed on 17 KPC-Kp isolates from this patient; single-nucleotide polymorphisms were analyzed and their implication in antimicrobial resistance and bacterial host adaptation investigated. Results The patient KPC-Kp strain diversified over 4.5 years at a rate of 7.5 substitutions per genome per year, resulting in broad phenotypic modifications. After 2 years of carriage, all isolates restored susceptibility to colistin. Higher expression of the fimbriae conferred the ability to produce more biofilm, and the isolate responsible for a bacteremia grew in human serum. The convergent mutations occurring in specific pathways, such as the respiratory chain and the cell envelope, revealed a complex long-term adaptation of KPC-Kp. Conclusions Broad genomic and phenotypic diversification and the parallel selection of pathoadaptive mutations might contribute to long-term carriage and virulence of KPC-Kp CG258 strains and to the dissemination of this clone. [ABSTRACT FROM AUTHOR]

Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) infections in the hemodialysis (HD) population are epidemiologically classified as healthcare-associated infections. The data about the clinical impact and bacterial characteristics of hospital-onset (HO)- and community-onset (CO)-MRSA in HD patients are scarce. The current study analyzed the difference in the clinical and molecular characteristics of HO-MRSA and CO-MRSA. Methods: We performed a retrospective review and molecular analysis of clinical isolates from 106 HD patients with MRSA bacteremia from 2009 to 2014. CA genotypes were defined as isolates carrying the SCCmec type IV or V, and HA genotypes were defined as isolates harboring SCCmec type I, II, or III. Results: CO-MRSA infections occurred in 76 patients, and 30 patients had HO-MRSA infections. There was no significant difference in the treatment failure rates between patients with CO-MRSA infections and those with HO-MRSA infections. CA genotypes were associated with less treatment failure (odds ratio [OR]: 0.18; 95% confidence interval [95% CI], 0.07–0.49; p = 0.001). For isolates with a vancomycin minimum inhibitory concentration (MIC) < 1.5 mg/L, the multivariate analysis revealed that HA genotypes and cuffed tunneled catheter use were associated with treatment failure. For isolates with a vancomycin MIC ≥1.5 mg/L, the only risk factor for treatment failure was a higher Pitt score (OR: 1.76; 95% CI, 1.02–3.05; p = 0.043). Conclusion: CA genotypes, but not the epidemiological classification of CO-MRSA, impacted the clinical outcome of MRSA bacteremia in the HD population. [ABSTRACT FROM AUTHOR]

Purpose: Bloodstream infections (BSIs) caused by Acinetobacter species have been extensively reported, however, which majorly focused on respiratory tract infections. The risk of mortality and the effect of early catheter removal on survival in catheter-related BSIs (CRBSIs) caused by Acinetobacter spp. remain unclear. This study aims to investigate that. Methods: This is a retrospective multicentric study conducted in Taiwan from 2012 to 2014. Patients with at least 1 positive blood culture and catheter culture for the same Acinetobacter spp., showing symptoms and signs of CRBSIs, were included (n = 119). Risk factors for 30-day mortality were analyzed using a logistic regression model. The characteristics of patients with early catheter removal (within 48 hours after CRBSIs) were compared to those without removal matching for age, sex, and disease severity. Results: There were no differences in 30-day mortality with regard to causative Acinetobacter spp., catheter type, site, and appropriateness of antimicrobial therapy. Patients with higher Acute Physiologic and Chronic Health Evaluation (APACHE) II scores (odds ratio [OR]: 1.12; 95% confidence interval [CI]: 1.02-1.23; P = .014), shock (OR: 6.43; 95% CI: 1.28-32.33; P = .024), and longer hospitalization before CRBSIs (OR: 1.04; 95% CI: 1.00-1.08; P = .027) had a significantly higher 30-day mortality rate. Early removal of catheters after CRBSIs was not associated with better survival benefits. Conclusion: Higher disease severity (APACHE II score), shock, and longer hospitalization before bacteremia were independently associated with a higher 30-day mortality in CRBSIs caused by Acinetobacter spp. In previous published guidelines, infected catheters were suggested to be removed in CRBSIs caused by gram-negative bacilli. Even though early removal of catheters did not associate with a better survival outcome in current results, it should be judiciously evaluated according to the clinical conditions and risks individually. For better elucidation of these issues, further well-controlled prospective study may be warranted. [ABSTRACT FROM AUTHOR]

Hypervirulent K. pneumoniae variants (hvKP) have been increasingly reported worldwide, causing metastasis of severe infections such as liver abscesses and bacteremia. The capsular serotype K2 hvKP strains show diverse multi-locus sequence types (MLSTs), but with limited genetics and virulence information. In this study, we report a hypermucoviscous K. pneumoniae strain, RJF293, isolated from a human bloodstream sample in a Chinese hospital. It caused a metastatic infection and fatal septic shock in a critical patient. The microbiological features and genetic background were investigated with multiple approaches. The Strain RJF293 was determined to be multilocis sequence type (ST) 374 and serotype K2, displayed a median lethal dose (LD50) of 1.5 × 102 CFU in BALB/c mice and was as virulent as the ST23 K1 serotype hvKP strain NTUH-K2044 in a mouse lethality assay. Whole genome sequencing revealed that the RJF293 genome codes for 32 putative virulence factors and exhibits a unique presence/absence pattern in comparison to the other 105 completely sequenced K. pneumoniae genomes. Whole genome SNP-based phylogenetic analysis revealed that strain RJF293 formed a single clade, distant from those containing either ST66 or ST86 hvKP. Compared to the other sequenced hvKP chromosomes, RJF293 contains several strain-variable regions, including one prophage, one ICEKp1 family integrative and conjugative element and six large genomic islands. The sequencing of the first complete genome of an ST374 K2 hvKP clinical strain should reinforce our understanding of the epidemiology and virulence mechanisms of this bloodstream infection-causing hvKP with clinical significance. [ABSTRACT FROM AUTHOR]

Background: Gram-negative bacilli are a cause of serious infections in the pediatric population. Carbapenem are the treatment of choice for infections caused by multidrug-resistant Gram-negative bacilli, but the emergence of carbapenem resistance has substantially reduced access to effective antimicrobial regimens. Children are a population vulnerable to bacterial infections and the emergence of resistance can worsen prognosis. The aim of this study is to describe the clinical and molecular characteristics of infections caused by carbapenem-resistant Gram-negative bacilli in pediatric patients from five tertiary-care hospitals in Medellín, Colombia.Methods: A cross-sectional study was conducted in five tertiary-care hospitals from June 2012 to June 2014. All pediatric patients infected by carbapenem-resistant Gram-negative bacilli were included. Clinical information for each patient was obtained from medical records. Molecular analyses included PCR for detection of bla VIM, bla IMP bla NDM, bla OXA-48 and bla KPC genes and PFGE and MLST for molecular typing.Results: A total of 59 patients were enrolled, most of them less than 1 year old (40.7 % n = 24), with a previous history of antibiotic use (94.9 %; n = 56) and healthcare-associated infections - predominately urinary tract infections (31.0 %; n = 18). Klebsiella pneumoniae was the most frequent bacteria (47.4 %), followed by Enterobacter cloacae (40.7 %) and Pseudomonas aeruginosa (11.9 %). For K. pneumoniae, KPC was the predominant resistance mechanism (85.7 %; n = 24) and ST14 was the most common clone (39.3 % n = 11), which included strains closely related by PFGE. In contrast, E. cloacae and P. aeruginosa were prevailing non-carbapenemase-producing isolates (only KPC and VIM were detected in 1 and 3 isolates, respectively) and high genetic diversity according to PFGE and MLST was found in the majority of the cases.Conclusions: In recent years, increasing carbapenem-resistant bacilli in children has become in a matter of great concern. It is important to conduct systemic surveillance and take measures to prevent dissemination of multidrug-resistant bacteria. [ABSTRACT FROM AUTHOR]

Objectives: Carbapenem-resistant Gram-negative bacteria (CRGNB) pose a clinical challenge. We attempted to estimate the mortality burden of CRGNB among haematological cancer patients.Methods: This was a retrospective cohort study. We included adult patients hospitalized in the haemato-oncological/bone marrow transplantation departments for chemotherapy, between 2008 and 2014, with Gram-negative aerobic bacteraemia. We compared patients with CRGNB and carbapenem-susceptible Gram-negative bacteraemia (CSGNB). The primary outcome was 14 day all-cause mortality. In addition, we assessed 1 year survival. Multivariable logistics regression analysis and adjusted Cox regression analysis were conducted. Analyses were adjusted to the propensity for CRGNB bacteraemia.Results: The cohort included mostly young patients (mean age 50.1 years) with acute leukaemia (264/423, 62.4%) and the median absolute neutrophil count at bacteraemia onset was 0 × 10(9)/L. The unadjusted 14 day mortality rate was higher for patients with CRGNB compared with CSGNB [45.6% (47/103) versus 15% (48/320), respectively (P < 0.001)]. Adjusting to baseline prognostic factors, infection characteristics and the propensity score retained a significant association between CRGNB and 14 day mortality (OR 5.14, 95% CI 2.32-11.38). Including only the first bacteraemic episode per patient, 1 year mortality was 74.7% (68/91) for patients with CRGNB versus 49.8% (119/239) for patients with CSGNB (P < 0.001). Adjusting for risk factors associated with 1 year mortality, the HR for mortality with CRGNB was 1.48 (95% CI 1-2.2). CRGNB bacteraemia was associated with several risk factors for mortality, including inappropriate empirical antibiotic treatment and less effective definitive antibiotics.Conclusions: This study demonstrated a significant adjusted association between CRGNB and mortality up to 1 year among haemato-oncological patients receiving chemotherapy. [ABSTRACT FROM AUTHOR]

Background: Acinetobacter ursingii bacteremia is rarely reported. We investigated the incidence and clinical features of A. ursingii bacteremia, performance of the identification system, and antimicrobial susceptibility of the isolates. Acinetobacter ursingii bacteremia patients were compared with A. baumannii bacteremia patients.Methods: In this 9-year retrospective study, A. ursingii was identified using 16S rRNA and 16S-23S rRNA internal transcribed spacer sequence analysis. The performances of the Vitek 2, Phoenix, and matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometer systems for identifying isolates were tested. Pulsed-field gel electrophoresis (PFGE) was used to determine the clonality of the isolates. The minimal inhibitory concentrations of the antimicrobials were determined using the Vitek 2 system.Results: Nineteen patients were identified. Acinetobacter ursingii was noted in 1.5-5.2 % of all Acinetobacter bacteremia cases. For the PFGE analysis, two isolates had smeared DNA, two had 93 % similarity, and 15 had similarity <80 %. Among 16 patients with complete medical records, 10 (62.5 %) had no identifiable source of A. ursingii bacteremia. Most patients (n = 12) had underlying malignant disease. Patients with A. ursingii bacteremia had lower Acute Physiology and Chronic Health Evaluation II scores than those with A. baumannii bacteremia (median [interquartile range], 17.1 [10.0-24.7] vs. 24.9 [14.6-35.1]). Patients with A. ursingii bacteremia were also less likely admitted to the intensive care unit than patients with A. baumannii bacteremia (18.8 % vs 63.5 %, p value < 0.01). About half of the patients with A. ursingii (50.8 %) and A. baumannii bacteremia (62.5 %) had received inappropriate antimicrobial therapy within 48 h after bacteremia onset. However, patients with A. ursingii bacteremia had significantly lower 14-day (6.25 % vs 29.8 %, p value = 0.04) and 28-day mortality rates (6.25 % vs 37.3 %, p value = 0.02) than patients with A. baumannii bacteremia. Nine isolates (47.4 %) were correctly identified as A. ursingii and the other 10 isolates (52.6 %) were incorrectly identified as A. lwoffii by the Vitek 2 system. The Phoenix system incorrectly identified all 19 isolates. The MALDI-TOF mass spectrometer system correctly identified all 19 isolates. All the A. ursingii isolates were resistant or showed intermediate susceptibility to ceftriaxone and ceftazidime, but were susceptible to levofloxacin and imipenem.Conclusions: Acinetobacter ursingii is a rare pathogen that mostly caused primary bacteremia in patients with malignancies. Patients with A. ursingii bacteremia had significantly lower disease severity and mortality rates than patients with A. baumannii bacteremia. [ABSTRACT FROM AUTHOR]

Background: Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia was associated with high mortality, but the risk factors associated with mortality remain controversial. Methods: A retrospective cohort study was designed. All patients with MRSA bacteremia admitted were screened and collected for their clinical presentations and laboratory characteristics. Minimum inhibitory concentration (MIC) and staphylococcal cassette chromosome mec (SCCmec) type of bacterial isolates were determined. Risk factors for mortality were analyzed. Results: Most MRSA isolates from the 189 enrolled patients showed reduced susceptibility to antibiotics, including MIC of vancomycin ≥ 1.5 mg/L (79.9%), teicoplanin ≥ 2 mg/L (86.2%), daptomycin ≥ 0.38 mg/L (73.0%) and linezolid ≥ 1.5 mg/L (64.0%). MRSA with vancomycin MIC ≥ 1.5 mg/L and inappropriate initial therapy were the two most important risk factors for mortality (both P < 0.05; odds ratio = 7.88 and 6.78). Hospital-associated MRSA (HA-MRSA), carrying SCCmec type I, II, or III, was associated with reduced susceptibility to vancomycin, teicoplanin or daptomycin and also with higher attributable mortality (all P < 0.05). Creeping vancomycin MIC was linked to higher MIC of teicoplanin and daptomycin (both P < 0.001), but not linezolid (P = 0.759). Conclusions: Giving empirical broad-spectrum antibiotics for at least 5 days to treat catheter-related infections, pneumonia, soft tissue infection and other infections was the most important risk factor for acquiring subsequent HA-MRSA infection. Choice of effective anti-MRSA agents for treating MRSA bacteremia should be based on MIC of vancomycin, teicoplanin and daptomycin. Initiation of an effective anti-MRSA agent without elevated MIC in 2 days is crucial for reducing mortality. [ABSTRACT FROM AUTHOR]

Background: We compared clinical outcomes between patients with healthcare-associated and community-acquired Klebsiella pneumoniae bacteraemia and identified predictors associated with mortality and high treatment cost in Hong Kong. Methods: This was a retrospective cohort study of patients with K. pneumoniae bacteraemia in a teaching hospital. Adult patients with K. pneumoniae in blood cultures were included. Demographics and clinical data were retrieved from medical records. Results: The analysis included 208 patients. The mean age was 68.6 ± 16.8 years. The Pitt bacteraemia score was 2.2 ± 2.8. In all, 54.8% cases were healthcare-associated infections. The 30-day mortality rate was 32.7%. The mortality rate of patients with healthcare-associated bacteraemia was significantly higher than for community-acquired cases (p < 0.001). Extended-spectrum β -lactamase (ESBL)-producing K. pneumoniae accounted for 15.4% of cases. Intraabdominal infection was the most common infection (32.7%). Prior use of immunosuppressive agents and antimicrobial therapy were two major predisposing factors for infection. The treatment cost was USD12 282 ± 11 751 and the length of hospitalization was 9.0 ± 6.7 days. Multivariate analysis showed that liver disease (odds ratio (OR) = 3.06; 95% confidence interval (CI) = 1.38 - 6.78), malignancy (OR = 6.86; 95% CI = 3.25 - 14.48), pneumonia (OR = 5.25; 95% CI = 2.05 - 13.41) and Pitt score - 1 (OR = 2.50; 95% CI = 1.25 - 5.00) were associated with mortality. Malignancy (OR = 2.94; 95% CI = 1.33 -6.49), Pitt score > 1 (OR = 4.15; 95% CI = 1.87 - 9.24) and age < 72 years (OR = 2.86; 95% CI = 1.35 - 5.88) were associated with high treatment cost. Conclusions: The 30-day mortality and treatment cost of patients with K. pneumoniae bacteraemia were high in Hong Kong. Based upon the risk factors identified, infection control and treatment algorithms for K. pneumoniae bacteraemia in patients with malignancy or liver disease are highly warranted. [ABSTRACT FROM AUTHOR]

Treatment of neonatal sepsis has become a challenge with the emergence of carbapenemase-producing bacteria. This study documents the trend of carbapenem susceptibility in Enterobacteriaceae that caused septicaemia in neonates over a five year period (2007–2011) and the molecular characterisation of Enterobacteriaceae resistant to carbapenems and cephalosporins. Hundred and five Enterobacteriaceae including Escherichia coli (n = 27), Klebsiella pneumoniae (n = 68) and Enterobacter spp. (n = 10) were isolated from blood of septicaemic neonates followed by antibiotic susceptibility tests, determination of MIC values, phenotypic and genotypic detection of β-lactamases. Carbapenem was the most active antimicrobial tested after tigecycline. CTX-M type was the most prevalent ESBL throughout the period (82%). New Delhi Metallo-β-lactamase-1 (NDM-1), which is a recent addition to the carbapenemase list, was the only carbapenemase identified in our setting. Fourteen percent of the isolates possessed blaNDM-1. Carbapenem non-susceptibility was first observed in 2007 and it was due to loss of Omp F/Ompk36 in combination with the presence of ESBLs/AmpCs. NDM-1 first emerged in E. coli during 2008; later in 2010, the resistance was detected in K. pneumoniae and E. cloacae isolates. NDM-1-producing isolates were resistant to other broad-spectrum antibiotics and possessed ESBLs, AmpCs, 16S-rRNA methylases, AAC(6′)-Ib-cr, bleomycin resistant gene and class 1 integron. Pulsed field gel electrophoresis of the NDM-1-producing isolates indicated that the isolates were clonally diverse. The study also showed that there was a significantly higher incidence of sepsis caused by NDM-1-harbouring isolates in the male sex, in neonates with low birth weight and neonates born at an extramural centre. However, sepsis with NDM-1-harbouring isolates did not result in a higher mortality rate. The study is the first to review the carbapenem resistance patterns in neonatal sepsis over an extended period of time. The study highlights the persistence of ESBLs (CTX-Ms) and the emergence of NDM-1 in Enterobacteriaceae in the unit. [ABSTRACT FROM AUTHOR]

Background Vancomycin is the standard first-line treatment for methicillin-resistant Staphylococcus aureus bacteremia. However, recent consensus guidelines recommend that clinicians consider using alternative agents such as daptomycin when the vancomycin minimum inhibitory concentration is greater than 1 ug/ml. To date however, there have been no head-to-head randomized trials comparing the safety and efficacy of daptomycin and vancomycin in the treatment of such infections. The primary aim of our study is to compare the efficacy of daptomycin versus vancomycin in the treatment of bloodstream infections due to methicillinresistant Staphylococcus aureus isolates with high vancomycin minimum inhibitory concentrations (greater than or equal to 1.5 ug/ml) in terms of reducing all-cause 60-day mortality. Methods/Design The study is designed as a multicenter prospective open label phase IIB pilot randomized controlled trial. Eligible participants will be inpatients over 21-years-old with a positive blood culture for methicillin-resistant Staphylococcus aureus with vancomycin minimum inhibitory concentration of greater than or equal to 1.5ug/ml. Randomization into intervention or active control arms will be performed with a 1:1 allocation ratio. We aim to recruit 50 participants over a period of two years. Participants randomized to the active control arm will receive vancomycin dose-while those randomized to the intervention arm will receive daptomycin. Participants will receive a minimum of 14 days study treatment. The primary analysis will be conducted on the intention-to-treat principle. The Fisher's exact test will be used to compare the 60-day mortality rate from index blood cultures (primary endpoint) between the two treatment arms, and the exact two-sided 95% confidence interval will be calculated using the Clopper and Pearson method. Primary analysis will be conducted using a two sided alpha of 0.05. Discussion If results from this pilot study suggest that daptomycin shows significant efficacy in the treatment of bloodstream infections due to methicillin-resistant Staphylococcus aureus isolates with high vancomycin minimum inhibitory concentrations, we aim to proceed with a larger scale confirmatory study. This would help guide clinicians and inform practice guidelines on the optimal treatment for such infections. [ABSTRACT FROM AUTHOR]

Background Klebsiella pneumoniae (KP) expressing hypermucoviscosity phenotype (HV-KP) has abundant capsular polysaccharide (CPS) and is capable of causing invasive syndrome. Sodium salicylate (SAL) reduces the production of CPS. The study was aimed to investigate the relationship between aspirin usage and KP-mediated invasive syndrome and the effect of SAL on HV-KP. Methods Patients with community-acquired KP bacteraemia were prospectively enrolled. KP-M1, a serotype-K1 HV-KP clinical isolate, was used in the following experiments: CPS production, HV-KP phenotype, and the effect of SAL on neutrophils phagocytosis. The effect of oral aspirin intake on the leukocyte bactericidal activity was evaluated. Results Patients infected by HV-KP and diabetic patients with poor glycemic control were at an increased risk for invasive syndrome (p < 0.01); those who had recent use of aspirin (p = 0.02) were at a lower risk. CPS production was significantly reduced in the presence of SAL. The HV-KP phenotype and resistance to neutrophil phagocytosis were both significantly reduced in the KP-M1 after incubation with SAL (p < 0.01). Aspirin treatment significantly enhanced the killing of KP-M1 by leukocytes (p < 0.01). Conclusion Treatment with SAL significantly reduces CPS production in HV-KP, thereby contributing to leukocyte phagocytosis and bactericidal activity against this pathogen. [ABSTRACT FROM AUTHOR]

Background Resistance among Klebsiella pneumoniae to most antibiotics is on the rise. Tigecycline has been considered as one of the few therapeutic options available to treat multidrug-resistant bacteria. We investigated the clinical and microbiological characteristics of tigecycline nonsusceptible K. pneumoniae bacteremia. Methods Adult patients with tigecycline non-susceptible K. pneumoniae bacteremia at a medical center in Taiwan over a 3-year period were enrolled. K. pneumoniae isolates were identified by the E-test using criteria set by the US Food and Drug Administration (FDA). Data on the clinical features of patients were collected from medical records. Genes for β-lactamases, antimicrobial susceptibilities and pulsed-field gel electrophoresis (PFGE) results were determined for all isolates. Results Of 36 patients, 27 had nosocomial bacteremia. Overall 28-day mortality was 38.9%. The MIC50 and MIC90 of tigecycline were 6 and 8 mg/L, respectively. No carbapenemase was detected among the 36 isolates. Twenty isolates carried extended spectrum β-lactamases and/or DHA-1 genes. No major cluster of isolates was found among the 36 isolates by PFGE. Intensive care unit onset of tigecycline non-susceptible Klebsiella pneumoniae bacteremia was the only independent risk factor for 28-day mortality. Conclusions The high mortality of patients with tigecycline non-susceptible K. pneumoniae bacteremia may suggest a critical problem. Further study to identify the possible risk factors for its development and further investigation of this type of bacteremia is necessary. [ABSTRACT FROM AUTHOR]

Capsule is an important virulence factor in bacteria. A total of 78 capsular types have been identified in Klebsiella pneumoniae. However, there are limitations in current typing methods. We report here the development of a new genotyping method based on amplification of the variable regions of the wzc gene. Fragments corresponding to the variable region of wzc were amplified and sequenced from 76 documented capsular types of reference or clinical strains. The remaining two capsular types (reference strains K15 and K50) lacked amplifiable wzc genes and were proven to be acapsular. Strains with the same capsular type exhibited ≧94% DNA sequence identity across the variable region (CD1-VR2-CD2) of wzc. Strains with distinct K types exhibited <80% DNA sequence identity across this region, with the exception of three pairs of strains: K22/K37, K9/K45, and K52/K79. Strains K22 and K37 shared identical capsular polysaccharide synthesis (cps) genes except for one gene with a difference at a single base which resulted in frameshift mutation. The wzc sequences of K9 and K45 exhibited high DNA sequence similarity but possessed different genes in their cps clusters. K52 and K79 exhibited 89% wzc DNA sequence identity but were readily distinguished from each other at the DNA level; in contrast, strains with the same capsular type as K52 exhibited 100% wzc sequence identity. A total of 29 strains from patients with bacteremia were typed by the wzc system. wzc DNA sequences confirmed the documented capsular type for twenty-eight of these clinical isolates; the remaining strain likely represents a new capsular type. Thus, the wzc genotyping system is a simple and useful method for capsular typing of K. pneumoniae. [ABSTRACT FROM AUTHOR]

Background Evidence for the impact of inappropriate antimicrobial therapy on bacteremia is mainly from studies in medical centers. We investigated the impact of inappropriate antimicrobial therapy on bacteremia in a community hospital. In particular, patients from the hospital's affiliated nursing home were sent to the hospital with adequate referral information. Methods We performed a retrospective study to collect data of patients with bacteremia in a community hospital in Taiwan from 2005 to 2007. Results A total of 222 patients with blood stream infection were diagnosed, of whom 104 patients (46.8%) died. The rate of initial inappropriate antibiotic prescriptions was high (59%). Multivariate analysis revealed that patients with initial inappropriate antibiotics, patients with ventilator support and patients requiring ICU care were the independent predictors for inhospital mortality. Patients referred from the hospital-affiliated nursing home and patients with normal WBC counts had better survival outcome. More than 80% cases infected with methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus faecalis received initial inappropriate antimicrobial therapy. With the longer delay to administer appropriate antibiotic, a trend of higher mortality rates was observed. Conclusions Bacteremia patients from a hospital-affiliated nursing home had a better prognosis, which may have been due to the adequate referral information. Clinicians should be aware of the commonly ignored drug resistant pathogens, and efforts should be made to avoid delaying the administration of appropriate antibiotic therapy. [ABSTRACT FROM AUTHOR]

Background: The need for mandatory confirmation of negative conversion in Klebsiella pneumoniae bacteremia (KpB) has not been adequately addressed. We conducted a retrospective case-control study of adult patients with KpB over a 5-year period in two tertiary-care hospitals to determine the risk factors for persistent bacteremia and to reevaluate the necessity of follow-up blood culture in KpB. Methods: Persistent KpB is defined as the finding of K. pneumoniae in more than two separate blood-culture samples for longer than a two-day period in a single episode. The case- and control-groups were patients with persistent and non-persistent KpB, respectively, and they were matched 1-to-3 according to age and gender. Results: Among 1068 KpB episodes analyzed after excluding polymicrobial infection and repeated KpB, follow-up blood cultures were performed in 862 cases (80.7%), 62 of which (7.2%) were persistent. Independent risk factors for persistence were intra-abdominal infection, higher Charlson's comorbidity weighted index score, prior solid organ transplantation, and unfavorable treatment response, which was defined as positivity for at least two parameters among fever, leukocytosis, and no decrease of C-reactive protein on the second day after initial culture. A proposed scoring system using four variables, namely, intra-abdominal infection, nosocomial KpB, fever and lack of C-reactive protein decrease, the last two being assessed on the second day after the initial blood culture, showed that only 4.9% of the patients with no risk factors or with only intra-abdominal infection had persistent KpB. Conclusions: Though persistent KpB is uncommon, follow-up blood culture was performed in as many as 80% of the cases in this study. A more careful clinical assessment is warranted to reduce the cost and patient inconvenience involved in follow-up blood culture. [ABSTRACT FROM AUTHOR]

Background: It is unknown whether there are differences between bacteremia caused by carbapenem resistant Acinetobacter baumannii (CRAB) and carbapenem resistant Acinetobacter nosocomialis (CRAN). This study aims to investigate the differences, especially in clinical outcomes, between patients with bacteremia caused by CRAB or CRAN. Methods: This is a 9-year retrospective study comparing the clinical manifestations, antimicrobial susceptibilities, and clinical outcomes of 71 patients with CRAB bacteremia and 64 patients with CRAN bacteremia. Results: Patients with CRAB were more likely to have hematologic malignancies and presented with more shock episodes than those with CRAN. CRAB isolates were more resistant to various classes of antimicrobials except colistin, and therefore the patients with CRAB bacteremia were more likely to receive inappropriate antimicrobial therapies. The 14-day mortality was significantly higher in patients with CRAB (40.8% vs. 14.1%; p = 0.001), and in this study, acquisition of CRAB was identified as an independent risk factor for mortality (odds ratio = 4.003; 95% confidence interval = 1.566-10.231; p = 0.004). Conclusions: CRAB and CRAN bacteremia are different in clinical characteristics, antimicrobial susceptibilities, and mortality rates. Genomic species identification should be performed in the study of carbapenem resistant Acinetobacters to better delineate the role of different species. [ABSTRACT FROM AUTHOR]