Risk factors for developing clinical infection with carbapenem-resistant Klebsiella pneumoniae in hospital patients initially only colonized with carbapenem-resistant K pneumoniae

doi:10.1016/j.ajic.2011.05.022

American Journal of Infection Control

Volume 40, Issue 5, June 2012, Pages 421-425

https://doi.org/10.1016/j.ajic.2011.05.022 Get rights and content

Background

This study examined predictors of carbapenem-resistant Klebsiella pneumoniae (CRKP) colonization and risk factors for the development of CRKP infection in patients initially only colonized with CRKP.

Methods

A total of 464 patients with CRKP rectal colonization (CRKP-RC) were identified. Two case-control studies were performed, one comparing risk factors for CRKP-RC in patients who did not develop CRKP infection (CRKP-IN) versus patients without CRKP-RC and CRKP-IN, and the other comparing CRKP-RC patients who did not develop CRKP-IN with those who did.

Results

Forty-two of the 464 colonized patients developed CRKP-IN. Multivariate analysis identified the following predictors for CRKP-RC: antibiotic therapy (odds ratio [OR], 5.76; P ≤ .0001), aminopenicillin therapy (OR, 7.753; P = .004), bedridden (OR, 3.09; P = .021), and nursing home residency (OR, 3.09; P = .013). Risk factors for CRKP-IN in initially CRKP-RC–positive patients were previous invasive procedure (OR, 5.737; P = .021), diabetes mellitus (OR, 4.362; P = .017), solid tumor (OR, 3.422; P = .025), tracheostomy (OR, 4.978; P = .042), urinary catheter insertion (OR, 4.696; P = .037), and antipseudomonal penicillin (OR, 23.09; P ≤ .0001).

Conclusions

We suggest that in patients with CRKP-RC, a strategy for preventing CRKP-IN might include limiting antipseudomonal penicillin and carbapenem use and preventing infections by closely following compliance with infection control bundles.

Section snippets

Methods

Soroka University Medical Center is a 1,000-bed acute tertiary care university teaching hospital with more than 85,000 admission-years, serving a population of more than 500,000 people in southern Israel. To control the nosocomial dissemination of CRKP, since May 2007 our institution has performed active surveillance cultures (using rectal cultures) in patients admitted from other institutions and/or nursing homes, in selective high-risk wards such as intensive care units, and in patients who

Risk factor analysis: CRKP-RC group versus CRKP-IN group

A total of 464 patients with CRKP colonization (70% male) were identified between May 2007 and January 2010 and had records for review. Of these patients, 42 (9%) developed CRKP infection. The median age was 72.5 years (range, 21-95 years) in the CRKP-RC group and 72 years (range, 19-91 years) in the CRKP-IN group. The total CRKP-IN incidence density was 1.57 per 10,000 patient-days. The sources of infection were urinary tract infection (57.5%), ventilator-associated pneumonia (30%), and

Discussion

To examine the acquisition and dissemination of CRKP, we conducted 2 retrospective matched case-control studies. The first CRKP-RC versus control group study aimed to identify the risk factors for acquisition of CRKP colonization in our institution. Considering that CRKP-colonized patients were widely distributed all around the hospital and that a number of cases were also identified by active surveillance at the time of hospital admission (community-acquired), assessment of predictors for CRKP

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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.
To explore the incidence and risk factors associated with CRKp infection following colonization.
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.
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).
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.
Fei-Yan-Qing-Hua decoction decreases hyperinflammation by inhibiting HMGB1/RAGE signaling and promotes bacterial phagocytosis in the treatment of sepsis
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Fei-Yan-Qing-Hua decoction (FYQHD), derived from the renowned formula Ma Xing Shi Gan tang documented in Zhang Zhong Jing's “Treatise on Exogenous Febrile Disease” during the Han Dynasty, has demonstrated notable efficacy in the clinical treatment of pneumonia resulting from bacterial infection. However, its molecular mechanisms underlying the therapeutic effects remains elusive.
This study aimed to investigate the protective effects of FYQHD against lipopolysaccharide (LPS) and carbapenem-resistant Klebsiella pneumoniae (CRKP)-induced sepsis in mice and to elucidate its specific mechanism of action.
Sepsis models were established in mice through intraperitoneal injection of LPS or CRKP. FYQHD was administered via gavage at low and high doses. Serum cytokines, bacterial load, and pathological damage were assessed using enzyme-linked immunosorbent assay (ELISA), minimal inhibitory concentration (MIC) detection, and hematoxylin and eosin staining (H&E), respectively. In vitro, the immunoregulatory effects of FYQHD on macrophages were investigated through ELISA, MIC, quantitative real-time PCR (Q-PCR), immunofluorescence, Western blot, and a network pharmacological approach.
The application of FYQHD in the treatment of LPS or CRKP-induced septic mouse models revealed significant outcomes. FYQHD increased the survival rate of mice exposed to a lethal dose of LPS to 33.3%, prevented hypothermia (with a rise of 3.58 °C), reduced pro-inflammatory variables (including TNF-α, IL-6, and MCP-1), and mitigated tissue damage in LPS or CRKP-induced septic mice. Additionally, FYQHD decreased bacterial load in CRKP-infected mice. In vitro, FYQHD suppressed the expression of inflammatory cytokines in macrophages activated by LPS or HK-CRKP. Mechanistically, FYQHD inhibited the PI3K/AKT/mTOR/4E-BP1 signaling pathway, thereby suppressing the translational level of inflammatory cytokines. Furthermore, it reduced the expression of HMGB1/RAGE, a positive feedback loop in the inflammatory response. Moreover, FYQHD was found to enhance the phagocytic activity of macrophages by upregulating the expression of phagocytic receptors such as CD169 and SR-A1.
FYQHD provides protection against bacterial sepsis by concurrently inhibiting the inflammatory response and augmenting the phagocytic ability of immune cells.
CRISPR/Cas13-assisted carbapenem-resistant Klebsiella pneumoniae detection
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Carbapenem-resistant Klebsiella pneumoniae (CRKP) is capable of causing serious community and hospital-acquired infections. However, currently, the identification of CRKP is complex and inefficient. Hence, this study aimed to develop methods for the early and effective identification of CRKP to allow reasonable antimicrobial therapy in a timely manner.
K. pneumoniae (KP)-, K. pneumoniae carbapenemase (KPC)- and New Delhi metallo-β-lactamase (NDM)- specific CRISPR RNAs (crRNAs), polymerase chain reaction (PCR) primers and recombinase-aided amplification (RAA) primers were designed and screened in conserved sequence regions. We established fluorescence and lateral flow strip assays based on CRISPR/Cas13a combined with PCR and RAA, respectively, to assist in the detection of CRKP. Sixty-one clinical strains (including 51 CRKP strains and 10 carbapenem-sensitive strains) were collected for clinical validation.
Using the PCR-CRISPR assay, the limit of detection (LOD) for KP and the blaKPC and blaNDM genes reached 1 copy/μL with the fluorescence signal readout. Using the RAA-CRISPR assay, the LOD could reach 10¹ copies/μL with both the fluorescence signal readout and the lateral flow strip readout. Additionally, the positivity rates of CRKP-positive samples detected by the PCR/RAA-CRISPR fluorescence and RAA-CRISPR lateral flow strip methods was 92.16% (47/51). The sensitivity and specificity reached 100% for KP and blaKPC and blaNDM gene detection. For detection in a simulated environmental sample, 1 CFU/cm² KP could be detected.
We established PCR/RAA-CRISPR assays for the detection of blaKPC and blaNDM carbapenemase genes, as well as KP, to facilitate the detection of CRKP.
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Acinetobacter baumannii (AB) poses a significant threat to critically ill patients in intensive care units (ICUs). Although an association between antibiotic exposure and resistant AB is reported in the literature, a synthesis of evidence in ICU patients is still lacking.
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Online databases were searched for cohort and case–control studies providing data on the association of interest. Carbapenem/multidrug-resistant AB isolation was compared with non-isolation; carbapenem/multidrug-resistant AB was compared with carbapenem/antibiotic-susceptible AB; and extensively drug-resistant AB isolation was compared with non-isolation. Each comparison was subjected to a restricted maximum likelihood random-effects meta-analysis per antibiotic class, estimating pooled ORs. Stratified meta-analyses were performed by study design, outcome type and association-measure adjustment.
Overall, 25 high-quality studies were retrieved. Meta-analyses showed that carbapenem/multidrug-resistant AB isolation was associated with previous exposure to aminoglycosides, carbapenems, third-generation cephalosporines, glycylcyclines, and nitroimidazoles. Increased risk of isolation of carbapenem/multidrug-resistant AB isolation vs carbapenem/antibiotic-susceptible AB was shown for prior exposure to aminoglycosides, antipseudomonal penicillins, carbapenems, fluoroquinolones, glycopeptides, and penicillins. Third-generation cephalosporin exposure increased the risk of extensively drug-resistant AB isolation vs non-isolation.
This systematic review clarifies the role of antibiotic use in antibiotic-resistant AB spread in ICUs, although for some antibiotic classes the evidence is still uncertain due to the small number of adjusted analyses, methodological and reporting issues, and limited number of studies. Future studies need to be carried out with standardized methods and appropriate reporting of multivariable models.
Molecular characteristics and virulence factors of carbapenem-resistant Klebsiella pneumoniae among pediatric patients in Shanghai, China
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We retrospectively investigated CRKP isolates among 92 pediatric patients (32 neonates and 60 non‑neonates) in 2019 and 2020 (59 and 33 isolates, respectively) to investigate the molecular characteristics and virulence factors of carbapenem-resistant Klebsiella pneumoniae (CRKP) isolated from pediatric patients,. All the CRKP isolates were subjected to antimicrobial susceptibility testing, string testing, molecular typing of virulence and carbapenemase genes, and multilocus sequence typing. Hypervirulent K. pneumoniae (Hvkp) was defined based on the detection of the regulator of mucoid phenotype A (rmpA).Sequence type 11 (ST11) accounted for the majority of infections in both neonates (37.5%) and non‑neonates (43.3%) (P > 0.05), whereas it increased from 30.5% (18/59) in 2019 to 60.6% (20/33) in 2020 (P < 0.05). Carbapenemase gene KPC-2 was predominant in both neonates and non‑neonates (46.9% vs. 51.7%, respectively), followed by New Delhi metallo-beta-lactamase 1 (NDM-1) (34.4% vs. 28.3%, respectively) (all P > 0.05). Compared to 2019, the proportion of bla_NDM-1 decreased (44.1% vs. 6.1%) (P < 0.001), while that of bla_KPC-2 increased (40.7% vs. 66.7%) (P = 0.017) in 2020. ybtS and iutA had a higher positivity rate in KPC-2 and ST11 producers (all P < 0.05); the KPC-2-, ybtS-, and iutA-positive isolates showed relatively higher resistance to fluoroquinolones and aminoglycosides, nitrofurantoin, and piperacillin/tazobactam, respectively. Furthermore, the combined expression (95.7%, 88/92) of carbapenemase and virulence-associated genes was detected, with the carbapenemase genes bla_KPC-2 and bla_TEM-1 combined with virulence-associated genes entB, mrkD, and ybtS accounting for the highest percentage (20.7%).Carbapenemase gene mutations in the CRKP strain from 2019 to 2020 highlight the importance of dynamic monitoring. The spread of hypervirulence-associated genes in CRKP strains and the high positivity rates of ybtS and iutA in KPC-2- and ST11-producing ones signify their high virulence potential in pediatric patients.
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The Netherlands Organization for Health Research and Development

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Major articleRisk factors for developing clinical infection with carbapenem-resistant Klebsiella pneumoniae in hospital patients initially only colonized with carbapenem-resistant K pneumoniae

Background

Methods

Results

Conclusions

Section snippets

Methods

Risk factor analysis: CRKP-RC group versus CRKP-IN group

Discussion

Clin Microbiol Infect

Am J Infect Control

J Hosp Infect

Guidelines for control of infections with carbapenemase-producing Enterobactereaceae in acute care facilities

MMWR Morb Mortal Wkly Rep

Carbapenem-nonsusceptible Enterobactereaceae in Europe: conclusions from a meeting of national experts

Euro Surveill

Outbreak of carbapenem-resistant Klebsiella pneumoniae in Puerto Rico associated with a novel carbapenemase variant

Infect Control Hosp Epidemiol

Carbapenem resistance among Klebsiella pneumoniae isolates: risk factors, molecular characteristics, and susceptibility patterns

Infect Control Hosp Epidemiol

Predictors of carbapenem-resistant Klebsiella pneumoniae acquisition among hospitalized adults and effect of acquisition on mortality

Antimicrob Agents Chemother

Outcomes of carbapenem-resistant Klebsiella pneumoniae infection and impact of antimicrobial and adjunctive therapies

Infect Control Hosp Epidemiol

Risk factors of carbapenem-resistant Klebsiella pneumoniae infections: a matched case-control study

J Antimicrob Chemother

Attributable mortality rate for carbapenem-resistant Klebsiella pneumoniae bacteremia

Infect Control Hosp Epidemiol

Performance standards for antimicrobial susceptibility testing: 16th informational supplement. Document M100-S16

Evaluation of methods to identify the Klebsiella pneumoniae carbapenase in Enterobactereaceae

J Clin Microbiol

Major article
Risk factors for developing clinical infection with carbapenem-resistant Klebsiella pneumoniae in hospital patients initially only colonized with carbapenem-resistant K pneumoniae