Dynamic cytokine profiles of bloodstream infection caused by Klebsiella pneumoniae in China
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SUBMITTER: Yu W
PROVIDER: S-EPMC11344948 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:ObjectivesThe aim of this study was to evaluate the characteristics of immunocyte associated with bloodstream infection (BSI) caused by Klebsiella pneumoniae (Kpn).MethodsPatients with BSI-Kpn were included from 2015 to 2022 in our hospital. Immunocyte subpopulations of enrolled BSI-Kpn patients were tested on the same day of blood culture using multicolor flow cytometry analysis. Antibiotic susceptibility test was determined by agar dilution or broth dilution method. All included isolates were subjected to whole genome sequencing and comparative genomics analysis. Clinical and genetic data were integrated to investigate the risk factors associated with clinical outcome.ResultsThere were 173 patients with non-duplicate BSI-Kpn, including 81 carbapenem-resistant Kpn (CRKP), 30 extended-spectrum β-lactamases producing Kpn (ESBL-Kpn), 62 none CRKP or ESBL-Kpn (S-Kpn). Among 68 ST11-CRKP isolates, ST11-O2v1:KL64 was the most common serotypes cluster (77.9%, 53/68), followed by ST11-OL101: KL47 (13.2%, 9/68). Compared with CSKP group, subpopulations of immunocyte in patients with CRKP were significantly lower (P < 0.01). In patients with ST11-O2v1:KL64 BSI-Kpn, the level of cytotoxic T lymphocytes (CD3 + CD8 +) is the highest, while the B lymphocytes (CD3-CD19 +) was the least. In addition, the level of immunocyte in patients with Kpn co-harbored clpV-ybtQ-qacE were lower than that in patients with Kpn harbored one of clpV, ybtQ or qacE and without these three genes. Furthermore, co-existence of clpV-ybtQ-qacE was independently associated with a higher risk for 30-day mortality.ConclusionsThe results demonstrate that patients with BSI-CRKP, especially for ST11-O2v1:KL64, exhibit lower leukomonocyte counts. In addition, BSI-Kpn co-harbored clpV-ybtQ-qacE is correlated to higher 30-day mortality.
| S-EPMC11191348 | biostudies-literature
Project description:We report the emergence of colistin resistance in Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae after 8 days of colistin-based therapy, resulting in relapse of bloodstream infection and death. Disruption of the mgrB gene by insertion of a mobile genetic element was found to be the mechanism, which was replicated in vitro after exposure to subinhibitory concentrations of colistin and meropenem.
| S-EPMC5913667 | biostudies-literature
Project description:We investigated the clinical features of bloodstream infections (BSIs) caused by Klebsiella pneumoniae harboring rmpA and molecular characteristics of the bacteria. We retrospectively investigated adult patients with K. pneumoniae BSI from January 2010 to March 2021 at Nagasaki University Hospital. A matched case-control study in a 1:3 ratio was conducted to clarify the clinical and bacterial characteristics of BSI caused by rmpA-positive K. pneumoniae compared with those caused by rmpA-negative isolates. Antimicrobial susceptibility testing and multilocus sequence typing (MLST) were performed for rmpA-positive isolates. The rmpA was detected in 36 (13.4%) of the 268 isolates. Of these 36 isolates, 31 (86.1%) harbored iucA and 35 (97.2%) each possessed peg-344 and iroB; capsular types were identified as K1 in 9 (25.0%) and K2 in 10 isolates (27.8%). Contrarily, of the 108 rmpA-negative isolates, which were matched for case-control studies, 5 isolates (4.6%) harbored iucA and 1 (0.9%) each possessed peg-344 and iroB; 2 (1.9%) and 3 isolates (2.8%) had K1 and K2 capsular types, respectively. Among the rmpA-positive isolates, ST23/K1 (eight isolates) was the most frequent, followed by ST412/non-K1/K2 (seven isolates), ST86/K2 (five isolates), and ST268/non-K1/K2 (four isolates). In a multivariate analysis using clinical factors, liver abscess positively correlated with rmpA-positive isolates, whereas biliary tract infection and use of anticancer drugs negatively correlated with rmpA-positive isolates in patients with K. pneumoniae BSI. Considering the correlation between rmpA-positive isolates and clinical features, rmpA can be used as a marker for understanding the pathophysiology of K. pneumoniae BSI.
| S-EPMC10121676 | biostudies-literature
Project description:Bloodstream infection (BSI), caused by Klebsiella pneumoniae, is associated with high morbidity and mortality, where the pks gene cluster plays a major role in their occurrence and prevalence. Information on the prevalence and characteristics of this gene cluster in K. pneumoniae is currently limited in mainland China. We therefore undertook a multicentre longitudinal study which revealed the prevalence, overall, community-onset and hospital-acquired BSI to be 20.5%, 28.3% and 13.0%, respectively. Compared to pks-negative, pks-positive isolates were significantly more susceptible to antimicrobial agents with a low incidence (5.1%) of multidrug-resistance and with infrequent extended-spectrum beta-lactamase (ESBL) production. Among pks-positive isolates, ST23 (78/117) and ST65 (20/117) were the dominant sequence types, and the majority harboured virulence genes. Community-onset BSI patients infected with pks-positive isolates had a higher proportion of liver abscesses and a lower proportion of biliary obstructions (P < 0.05). The pks-positive isolates were mostly sporadic in the phylogenetic tree, with a 65.8 and 47.0 average allele difference between Clade 1 and Clade 2, respectively. We concluded that although pks-positive K. pneumoniae were generally susceptible to antimicrobials, the high prevalence of such isolates in community cases and the genotoxicity, merits further investigation.
| S-EPMC7118716 | biostudies-literature
Project description:Aztreonam/avibactam (AZA), as one of the novel β-lactamases and β-lactamase inhibitor combinations, is considered to be a promising option for bloodstream infection (BSI) of carbapenem-resistant Klebsiella pneumoniae (CR-Kp). However, decreased susceptibility of AZA activity in Enterobacterales has been reported. The aim of this study was to identify the mechanisms of BSI CR-Kp with decreased susceptibility of AZA (minimal inhibitory concentration above 16/4 mg/L) (AZAH-Kp). Nine BSI AZAH-Kp isolates were screened from 317 CR-Kp isolates in Blood Bacterial Resistant Investigation Collaborative System (BRICS) program. Whole genome sequencing, bioinformatics analysis, and the relative expression of blaKPC , ompK35, and ompK37 were explored for CR-Kp with decreased susceptibility to AZA. The results revealed that elevated inhibitory concentration of AZA has emerged in CR-Kp before previous clinical exposure. In addition, decreased AZA susceptibility was associated with higher KPC expression and changes in OmpK35-37.
| S-EPMC9257070 | biostudies-literature
Project description:Introduction: Polymyxin B is a last-line therapy for carbapenem-resistant microorganisms. However, a lack of clinical pharmacokinetic/pharmacodynamic (PK/PD) data has substantially hindered dose optimization and breakpoint setting. Methods: A prospective, multi-center clinical trial was undertaken with polymyxin B [2.5 mg/kg loading dose (3-h infusion), 1.25 mg/kg/12 h maintenance dose (2-h infusion)] for treatment of carbapenem-resistant K. pneumoniae (CRKP) bloodstream infections (BSI). Safety, clinical and microbiological efficacy were evaluated. A validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was applied to determine the concentrations of polymyxin B in blood samples. Population pharmacokinetic (PK) modeling and Monte Carlo simulations were conducted to examine the susceptibility breakpoint for polymyxin B against BSI caused by CRKP. Results: Nine patients were enrolled and evaluated for safety. Neurotoxicity (5/9), nephrotoxicity (5/9), and hyperpigmentation (1/9) were recorded. Blood cultures were negative within 3 days of commencing therapy in all 8 patients evaluated for microbiological efficacy, and clinical cure or improvement occurred in 6 of 8 patients. Cmax and Cmin following the loading dose were 5.53 ± 1.80 and 1.62 ± 0.41 mg/L, respectively. With maintenance dosing, AUCss,24 h was 79.6 ± 25.0 mg h/L and Css,avg 3.35 ± 1.06 mg/L. Monte Carlo simulations indicated that a 1 mg/kg/12-hourly maintenance dose could achieve >90% probability of target attainment (PTA) for isolates with minimum inhibitory concentration (MIC) ≤1 mg/L. PTA dropped substantially for MICs ≥2 mg/L, even with a maximally recommended daily dose of 1.5 mg/kg/12-hourly. Conclusion: This is the first clinical PK/PD study evaluating polymyxin B for BSI. These results will assist to optimize polymyxin B therapy and establish its breakpoints for CRKP BSI.
| S-EPMC9800617 | biostudies-literature
Project description: Not available
| S-EPMC8574888 | biostudies-literature
Project description:Klebsiella pneumoniae is a significant infectious pathogen that causes bloodstream infections. This study aimed to genetically characterize a novel sequence type 4523 (ST4523) multidrug-resistant (MDR) K. pneumoniae strain recovered from the blood of a 79-year-old Chinese female patient with severe pneumonia and chronic obstructive pulmonary disease who ultimately died of the infection. The susceptibility testing results showed that strain 18SHX180 is nonsusceptible to cephalosporin, carbapenems, combinations of β-lactam and β-lactamase inhibitors, levofloxacin, and colistin and is only susceptible to amikacin. The phylogenetic structure showed that strain 18SHX180 belongs to a novel sequence type, ST4523, and capsule serotype K111. ST4523 is closely related to ST11, the most dominant clone of clinical carbapenem-resistant K. pneumoniae in China. ST4523 has 2 single-base variants in mdh and phoE. 18SHX180 showed medium virulence in Galleria mellonella and a mouse intraperitoneal infection model. PacBio Sequel and Illumina sequencing were performed to analyze the genetic characterization of 18SHX180, which contains 2 plasmids (pSHX180-NDM5 and pSHX180-1). pSHX180-NDM5 exhibits 86% coverage and 100% identity with 3 blaNDM-5-carrying plasmids and contains an additional region coding for the frmRAB operon, which permits bacteria to sense and detoxify formaldehyde. pSHX180-1 is responsible for the MDR phenotype: it carries 11 categories of genes for antimicrobial resistance [aadA16, aph(3″)-Ib, aph(6)-Id, blaSHV-182, blaTEM-1A, qacE, aac(6')-Ib-cr, mph(A), floR, qnrB6, arr-3, sul, sul2], all of which are associated with transposons and integrons located in three accessory resistance regions. The novel ST4523 K. pneumoniae strain could threaten the control of antimicrobial resistance, and its discovery calls attention to the genetic evolution of bacteria. IMPORTANCE Klebsiella pneumoniae is a significant infectious pathogen causing bloodstream infections. Due to the dissemination of carbapenemase genes, the incidence of carbapenem-resistant K. pneumoniae (CRKP) has increased, with high morbidity and mortality rates in immunocompromised patients. Here, we reported a novel ST4523 blaNDM-5-bearing CRKP strain initially recovered from a 79-year-old female who died of both a lower respiratory tract infection and bloodstream infection. We also describe the genetic and phenotypic characteristics of this strain. This study provides important insights into the genetic evolution of ST11 K. pneumoniae.
| S-EPMC9603328 | biostudies-literature
Project description:BackgroundBloodstream infection of Klebsiella pneumoniae (BSI-KP) were associated with increased mortality. Klebsiella pneumoniae was tested to susceptible to colistin by E-test and broth microdilution method in clinical laboratory. This study aimed to assess the efficacy of colistin versus tigecycline, carbapenem monotherapy and combination in the treatment of BSI-KP.MethodsElectronic databases such as PubMed, Web of Science and Embase were searched. The last search was in November 24th, 2022, addressing the colistin, carbapenems and tigecycline monotherapy and combination treatments in patients with BSI-KP. The primary outcomes were 30-day or 28-day mortality. OR where available with 95% CI were pooled in random-effects meta-analysis.ResultsFollowing the outlined search strategy, a total of 658 articles were identified from the initial database searching. Six studies, 17 comparisons were included. However, they all were observational design, lacking high-quality randomized controlled trials (RCTs). Moderate or low-quality evidences suggested that colistin monotherapy was associated with an OR = 1.35 (95% CI = 0.62-2.97, P = 0.45, Tau2 = 0.00, I2 = 0%) compared with tigecycline monotherapy, OR = 0.81 (95% CI = 0.27-2.45, P = 0.71, Tau2 = 0.00, I2 = 0%) compared with carbapenem monotherapy. Compared with combination with tigecycline or carbapenem, Colistin monotherapy resulted in OR of 3.07 (95% CI = 1.34-7.04, P = 0.008, Tau2 = 0.00, I2 = 0%) and 0.98 (95%CI = 0.29-3.31, P = 0.98, Tau2 = 0.00, I2 = 0% ), respectively.ConclusionsColistin, carbapenem and tigecycline monotherapy showed similar treatment effects in patients who suffered from BSI-KP. Compared with colistin monotherapy, colistin combined tigecycline therapy might play the synergism effects.Trial registrationretrospectively registered.
| S-EPMC10845734 | biostudies-literature
Project description:BACKGROUND:Bloodstream infections (BSIs) by Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae (Kp) are associated with high mortality. The aim of this study is to assess the relationship between time to administration of appropriate antibiotic therapy and the outcome of patients with BSI due to KPC-Kp hospitalized in intensive care unit (ICU). METHODS:An observational study was conducted in the ICUs of two academic centers in Italy. Patients with KPC-Kp bacteremia hospitalized between January 2015 to December 2018 were included. The primary outcome was the relationship between time from blood cultures (BC) collection to appropriate antibiotic therapy and 30-day mortality. The secondary outcome was to evaluate the association of different treatment regimens with 30-day mortality and a composite endpoint (30-day mortality or nephrotoxicity). A Cox regression analysis to identify factors independently associated with 30-day mortality was performed. Hazard ratio (HR) and 95% confidence interval (CI) were calculated. RESULTS:A total of 102 patients with KPC-Kp BSI were included. The most common sources of infection were intra-abdominal (23.5%), urinary tract (20.6%), and skin and skin structure (17.6%). The 30-day mortality was 45%. Median time to appropriate antibiotic therapy was shorter in patients who survived (8.5 h [IQR 1-36]) versus those who died (48 h [IQR 5-108], p = 0.014). A propensity score matching showed that receipt of an in vitro active therapy within 24 h from BC collection was associated with lower 30-day mortality (HR = 0.36, 95% CI: 0.188-0.690, p = 0.0021). At Cox regression analysis, factors associated with 30-day mortality were primary bacteremia (HR 2.662 [95% CI 1.118-6.336], p = 0.027), cardiovascular disease (HR 2.196 [95% CI 1.082-4.457], p = 0.029), time (24-h increments) from BC collection to appropriate therapy (HR 1.382 [95% CI 1.132-1.687], p = 0.001), SOFA score (HR 1.122 [95% CI 1.036-1.216], p = 0.005), and age (HR 1.030 [95% CI 1.006-1.054], p = 0.012). Ceftazidime-avibactam-containing regimens were associated with reduced risk of composite endpoint (30-day mortality OR nephrotoxicity) (HR 0.231 [95% CI 0.071-0.745], p = 0.014) compared to colistin-containing regimens. CONCLUSIONS:Time to appropriate antibiotic therapy is an independent predictor of 30-day mortality in patients with KPC-Kp BSI. Appropriate antibiotic therapy should begin within 24 h from the collection of BC.
| S-EPMC6993311 | biostudies-literature