UNASSIGNED: Due to scarce therapeutic options, hospital-acquired infections caused by Klebsiella pneumoniae (KP), particularly carbapenem-resistant KP (CRKP), pose enormous threat to patients\' health worldwide. This study aimed to characterize the epidemiology and risk factors of CRKP among nosocomial KP infections.
UNASSIGNED: MEDLINE, Embase, PubMed, and Google Scholar were searched for studies reporting CRKP prevalence from inception to 30 March 2023. Data from eligible publications were extracted and subjected to meta-analysis to obtain global, regional, and country-specific estimates. To determine the cause of heterogeneity among the selected studies, prespecified subgroup analyses and meta-regression were also performed. Odds ratios of CRKP-associated risk factors were pooled by a DerSimonian and Laird random-effects method.
UNASSIGNED: We retained 61 articles across 14 countries and territories. The global prevalence of CRKP among patients with KP infections was 28.69% (95% CI, 26.53%-30.86%). South Asia had the highest CRKP prevalence at 66.04% (95% CI, 54.22%-77.85%), while high-income North America had the lowest prevalence at 14.29% (95% CI, 6.50%-22.0%). In the country/territory level, Greece had the highest prevalence at 70.61% (95% CI, 56.77%-84.45%), followed by India at 67.62% (95% CI, 53.74%-81.79%) and Taiwan at 67.54% (95% CI, 58.65%-76.14%). Hospital-acquired CRKP infections were associated with the following factors: hematologic malignancies, corticosteroid therapies, intensive care unit stays, mechanical ventilations, central venous catheter implantations, previous hospitalization, and antibiotic-related exposures (antifungals, carbapenems, quinolones, and cephalosporins).
UNASSIGNED: Study findings highlight the importance of routine surveillance to control carbapenem resistance and suggest that patients with nosocomial KP infection have a very high prevalence of CRKP.

BACKGROUND: Carbapenem-resistant Klebsiella pneumoniae (CRKp) is a major pathogen causing nosocomial infections with a high mortality and poor prognosis. Gastrointestinal carriage has been acknowledged as the primary reservoir of CRKp infections.
OBJECTIVE: To explore the incidence and risk factors associated with CRKp infection following colonization.
METHODS: The PubMed, Web of Science, and Cochrane Library databases were searched for relevant articles published between December 1998 and June 2023. Pooled estimates with a 95% confidence interval (CI) were calculated for the incidence rate, whereas pooled odds ratios (ORs) were calculated for the risk factors for which the OR was reported in three or more studies.
RESULTS: Fourteen studies were included in the review with 5483 patients for the assessment of incidence, whereas seven of these studies with 2170 patients were included for the analysis of risk factors. In the meta-analysis, the incidence of CRKp infections after colonization was 23.2% (17.9-28.5). Additionally, three independent risk factors for subsequent CRKp infections were identified as admission to the intensive care unit (ICU) (2.59; 95% CI: 1.64-4.11), invasive procedures (2.53; 95% CI: 1.59-4.03), and multi-site colonization (6.24; 95% CI: 2.38-16.33).
CONCLUSIONS: This review reveals the incidence of CRKp infections in rectal carriers in different countries, emphasizing the role of rectal colonization with CRKp as an important source of nosocomial infections. Significantly, the risk factors indicated in this review can assist clinicians in identifying CRKp carriers with an elevated risk of subsequent infections, thereby enabling further measures to be taken to prevent nosocomial infections.

A 22-year-old lady underwent penetrating keratoplasty for serious keratoconus. The following day, it was complicated by the development of infectious endophthalmitis. The source of infection was identified as carbapenem-resistant Klebsiella pneumoniae. The donor corneal button might be playing a role in infection transmission due to carbapenem-resistant Klebsiella pneumoniae in a sputum culture when the donor was still alive. Nosocomial infections were typically severe, rapidly progressive, and difficult to treat. Finally, the patient underwent therapeutic penetrating keratoplasty again with complete resolution of the infection.

BACKGROUND: Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections are a significant public health issue. CRKP infections can increase the mortality of severely ill hospitalised patients and elevate the financial burden of their hospitalisation globally. Colistin and tigecycline are the main antimicrobials which have been widely used for the treatment of CRKP infections. However, novel antimicrobials have been recently launched. Ceftazidime-avibactam (CAZ-AVI) seems one of the most efficient ones.
OBJECTIVE: The aim of the current systematic literature review and meta-analysis is to assess the efficacy and safety of CAZ-AVI compared to other antimicrobials in adult patients (aged >18) with CRKP infection.
METHODS: All data were retrieved using PubMed/Medline, the Web of Science and Cochrane library. The main outcome was the effective treatment of CRKP infection or the microbiological eradication of CRKP in the culture of biological samples. Secondary outcomes included the impact on 28- or 30-day mortality and adverse effects, if available. Pooled analysis was conducted using Review Manager v. 5.4.1 software (RevMan). The level of statistical significance was set at p < 0.05.
RESULTS: CAZ-AVI was proved more effective than other antimicrobials against CRKP infections and CRKP bloodstream infections (p < 0.00001 and p < 0.0001, respectively). Patients in the CAZ-AVI arm displayed statistically lower 28- and 30-day mortality rates (p = 0.002 and p < 0.00001, respectively). Concerning the microbiological eradication, no meta-analysis was feasible due to high heterogeneity.
CONCLUSIONS: The promotion of CAZ-AVI for treating CRKP infections over other antimicrobials seems favourable. However, there is a long way ahead to reveal additional scientific findings to further strengthen this statement.

OBJECTIVE: The aim of this study was to describe our experience of a combination treatment including meropenem/vaborbactam (M/V) plus aztreonam (ATM) for bloodstream infections (BSIs) due to ceftazidime/avibactam-resistant Klebsiella pneumoniae (CAZ/AVI-R-Kp), for which gene typing was not available at the time the blood culture (BC) results were obtained.
METHODS: Between 20 July and 22 August 2021, in our hospital laboratory, the molecular test for carbapenemase gene typing was not available. All Gram-negative bloodstream infections were recorded, and characteristics of patients were analysed. Among them, three patients had positive BCs for CAZ/AVI-R-Kp, and the empirical therapy was switched to M/V plus ATM pending phenotypic testing of sensitivity to M/V. Therapy was subsequently targeted on the basis of the results of this test.
RESULTS: KPC and NDM represent the most prevalent carbapenemases in our polyclinic. Three patients with CAZ/AVI-R-Kp sepsis were treated with M/V plus ATM not knowing the carbapenemase gene. Two had an NDM-Kp infection for which, upon obtaining the result of sensitivity to M/V, combination therapy was maintained. The third had KPC-Kp infection for which ATM was discontinued, after the acquisition of an antibiogram reporting full sensitivity to M/V (MIC = 0.25 mg/L). One patient with NDM-Kp infection died due to complications of the underlying disease for which he was hospitalised.
CONCLUSIONS: Meropenem/vaborbactam plus ATM and subsequent de-escalation could represent a possible therapeutic strategy in severe CAZ/AVI-R-Kp infections when carbapenemase gene typing is not rapidly available.

BACKGROUND: Cases of carbapenem-resistant Klebsiella pneumoniae infection have been increasing. Patients with carbapenem-resistant Klebsiella pneumoniae infection have a poor prognosis and a high mortality rate. Identification of potential risk factors associated with carbapenem-resistant Klebsiella pneumoniae infection-related mortality may help improve patient outcomes.
METHODS: Embase, PubMed, and the Cochrane Library databases were searched to identify articles describing predictors of mortality in patients with carbapenem-resistant Klebsiella pneumoniae infection. The quality of articles was assessed with the Newcastle-Ottawa Scale score (NOS). Review Manager was used for statistical analyses.
RESULTS: Twenty-seven observational studies were included in the analysis. Factors associated with higher mortality were septic shock [odds ratio (OR): 4.41, 95% CI: 3.17-6.15], congestive heart failure (OR: 2.65, 95% CI: 1.71-4.13), chronic obstructive pulmonary disease (COPD; OR: 2.43, 95% CI: 1.87-3.15), chronic kidney disease (CKD; OR: 1.78, 95% CI: 1.43-2.22), diabetes mellitus (OR: 1.41, 95% CI: 1.16-1.72), mechanical ventilation (OR: 1.65, 95% CI: 1.25-2.18), and inappropriate empirical antimicrobial treatment (OR: 1.25, 95% CI: 1.03-1.52). The average Acute Physiology and Chronic Health Evaluation (APACHE) II score at the time of diagnosis of carbapenem-resistant Klebsiella pneumoniae infection was considerably higher in patients who did not survive than in those who survived (weighted mean difference: 5.86, 95% CI: 2.46-9.26).
CONCLUSIONS: Patient condition, timing appropriate antimicrobial treatment, and disease severity according to the APACHE II score are the most important risk factors for death in patients with carbapenem-resistant Klebsiella pneumoniae infection. Our finding may help predict patients\' outcomes and improve management for them.
UNASSIGNED: 20210417EuEGX/INPLASY2020100037.

This meta-analysis was performed to compare polymyxin monotherapy and polymyxin-based combination therapy for carbapenem-resistant Klebsiella pneumoniae (CR-KP) infections.
We conducted searches on MEDLINE, Embase and Cochrane Collaborative database for both observational studies and randomised controlled trials (RCTs) comparing polymyxin monotherapy with polymyxin-based combination therapy in patients with CR-KP infection. The primary outcome was mortality. We divided all included studies into several groups according to different combination-combination and different infection types. The odds ratio (OR) and 95% confidence intervals (CI) were calculated for outcome analysis.
Ten studies with 481 patients were included. Polymyxin monotherapy was associated with higher mortality than polymyxin-based combination therapy in treatment of CR-KP bloodstream infections (BSI) (OR 1.93, 95% CI 1.14-3.27, P = 0.01) and ventilator-associated pneumonia (VAP)/hospital-acquired pneumonia (HAP) (OR 3.82, 95% CI 1.15-12.71, P = 0.03). In subgroup analysis of different combinations, mortality was significantly higher with polymyxin monotherapy compared with combination therapy with tigecycline (OR 1.88, 95% CI 1.05-3.37, P = 0.03), or with cabapenem (OR 3.11, 95% CI 1.25-7.74, P = 0.01), but no differences were found in combinations with aminoglycosides (OR 1.29, 95% CI 0.72-2.29, P = 0.38). Three-drug combination therapy including polymyxin was also associated with significant survival benefit (OR 3.86, 95% CI 1.60-9.32, P = 0.003).
Polymyxin-based combination therapy provides significant survival benefit in treatment of CR-KP, which appears to be more pronounced when a carbapenem or tigecycline is included in the regimen.

Sequence type 11 (ST11) carbapenem-resistant Klebsiella pneumoniae (CRKP) has become the dominant clone in China. In this review, we trace the prevalence of ST11 CRKP in the China Antimicrobial Surveillance Network (CHINET), the key antimicrobial resistance mechanisms and virulence evolution. The recent emergence of ST11 carbapenem-resistant hypervirulent K. pneumoniae (CR-hvKP) strains in China due to the acquisition of a pLVPK-like virulence plasmid, which may cause severe infections in relatively healthy individuals that are difficult to treat with current antibiotics, has attracted worldwide attention. There is a very close linkage among IncF plasmids, NTEKPC and ST11 K. pneumoniae in China. Hybrid conjugative virulence plasmids are demonstrated to readily convert a ST11 CRKP strain to a CR-hvKP strain via conjugation. Understanding the molecular evolutionary mechanisms of resistance and virulence-bearing plasmids as well as the prevalence of ST11 CRKP in China allows improved tracking and control of such organisms.

Infections with multi-drug resistant (MDR) bacteria including carbapenem-resistant Klebsiella pneumoniae are emerging worldwide but are difficult to treat with the currently available antibiotic compounds and therefore constitute serious threats to human health. This prompted us to perform a literature survey applying the MEDLINE database and Cochrane Register of Controlled Trials including clinical trials comparing different treatment regimens for infections caused by carbapenem-resistant K. pneumoniae. Our survey revealed that a combined application of antibiotic compounds such as meropenem plus vaborbactam, meropenem plus colistin and carbapenem plus carbapenem, resulted in significantly increased clinical cure and decreased mortality rates as compared to respective control treatment. However, further research on novel antibiotic compounds, but also on antibiotic-independent molecules providing synergistic or at least resistance-modifying properties needs to be undertaken in vitro as well as in large clinical trials to provide future options in the combat of emerging life-threatening infections caused by MDR bacteria.