OBJECTIVES: To systematically assess the risk factors for the colonization or infection of carbapenem-resistant Enterobacteriaceae in children. METHODS: PubMed, Web of Science, China National Knowledge Infrastructure Database, Wanfang Data, China Biology Medicine disc were searched to obtain the articles on risk factors for the colonization or infection of carbapenem-resistant Enterobacteriaceae in children published up to May 31, 2021. RevMan 5.3 software was used to perform the Meta analysis. RESULTS: A total of 13 articles were included, with 1 501 samples in total. The Meta analysis showed that indwelling gastric tube (OR=4.91), tracheal intubation (OR=5.03), central venous catheterization (OR=3.75), indwelling urinary catheterization (OR=4.11), mechanical ventilation (OR=3.09), history of hospitalization in the intensive care unit (OR=2.39), history of surgical operation (OR=3.22), previous use of third-generation cephalosporins (OR=2.62), previous use of carbapenem antibiotics (OR=3.82), previous use of glycopeptide antibiotics (OR=3.48), previous use of β-lactamase inhibitors (OR=2.87), previous use of antifungal drugs (OR=2.48), previous use of aminoglycoside antibiotics (OR=2.54), and Apgar score ≤7 at 1 minute after birth (OR=2.10) were risk factors for the colonization or infection of carbapenem-resistant Enterobacteriaceae in children (P<0.05). CONCLUSIONS Invasive operations, history of hospitalization in the intensive care unit, previous use of antibiotics such as carbapenem antibiotics, and Apgar score ≤7 at 1 minute after birth are risk factors for the colonization or infection of carbapenem-resistant Enterobacteriaceae in children.
Anti-Bacterial Agents/therapeutic use* ; Carbapenem-Resistant Enterobacteriaceae ; Carbapenems/pharmacology* ; Child ; Enterobacteriaceae Infections/microbiology* ; Humans ; Risk Factors

To investigate the carbapenemases distribution of carbapenem-resistant Klebsiella pneumoniae (CRKP) in the intensive care unit, and the clinical characteristics between carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) and carbapenem-resistant non-hypervirulent Klebsiella pneumoniae (CR-non-hvKP) were compared. A total of 53 non-repetitive CRKP strains isolated from 49 patients in the intensive care unit of the Second Affiliated Hospital of Xi'an Jiaotong University from May 2020 to March 2021 were retrospectively studied. The carbapenemase inhibitor enhancement test was used for screening carbapenemase-producing strains, and the string test was carried out to screen the hypermucoviscosity phenotype. Using PCR to detect five main carbapenemase genes (bla_KPC-2, bla_NDM, bla_IMP , bla_VIM and bla_OXA-48-like), common serotype (K1 and K2) and virulence gene (rmpA and iutA). Treated the strains with both rmpA and iutA genes as hypervirulent Klebsiella pneumonia (hvKP), and the whole genome sequencing of CR-hvKP was completed. At the same time, the clinical data of 49 patients were sorted out, and the differences in clinical characteristics of CR-hvKP and CR-non-hvKP infected patients were compared using the independent sample t test, Mann-Whitney U test, chi-square test or Fisher's exact probability test. CRKP isolated from the intensive care unit were extensively drug resistance and still had a good sensitivity to polymyxin B and tigecycline. Producing carbapenemases were the main resistance mechanism of CRKP (52/53, 98.1%). Of the 53 CRKP strains, except for 1strain that did not detect carbapenemase, at least one carbapenemase resistance gene was detected in the remaining 52 CRKP strains, of which 45 strains carried an enzyme, including 36 bla_KPC-2 (36/53, 67.9%), 8 bla_NDM (8/53, 15.1%), 1 bla_IMP (1/53, 1.9%), and 7 strains carried with both bla_KPC-2 and bla_NDM (7/53, 13.2%). String test and virulence gene showed that 7 CR-hvKP strains (13.2%) were detected in 53 CRKP strains, and two of which were hypermucoviscosity phenotype. Sequencing results revealed that CR-hvKP were mainly ST11 type. Almost all patients with CR-hvKP infection were over 60 years old (7/7), with invasive treatment (7/7), pulmonary infection with hypermucoviscosity phenotype (2/7) and high mortality (5/7); and the percentage of neutrophils in patients with CR-hvKP infection (86.44±4.70) % was higher than those patients with CR-non-hvKP infection (78.90±19.15) %, the difference was statistically significant (t=-2.225, P=0.032). The CR-hvKP strains in the intensive care unit mainly produced KPC-2 enzyme, with K2 capsular serotype and ST11 type. It is necessary to strengthen the monitoring and control of the CR-hvKP strain to prevent the co-evolution of drug-resistant and hypervirulent strains.
Anti-Bacterial Agents/therapeutic use* ; Carbapenems/pharmacology* ; Humans ; Intensive Care Units ; Klebsiella pneumoniae/genetics* ; Middle Aged ; Retrospective Studies

Objective: Analysis and investigation of pathogenic characteristics of polymyxin-and carbapenem-resistant Klebsiella pneumoniae (PR-CRKP). Methods: A total of 23 PR-CRKP strains isolated from clinical specimens from the General Hospital of Southern Theater Command from March 2019 to July 2021 were retrospectively collected, Whole-genome sequencing was performed on 23 PR-CRKP strains, resistance genes were identified by comparison of the CARD and the ResFinder database, high-resolution typing of PR-CRKP strains was analyzed by core genomic multilocus sequencing (cgMLST) and single nucleotide polymorphism (SNP); polymyxin resistance genes were determined by PCR and sequencing. Results: All PR-CRKP strains were KPC-2 producing ST11 types. cgMLST results showed that the evolutionary distance between the PR-CRKP strains and Klebsiella pneumoniae in mainland China was 66.44 on average, which is more closely related than foreign strains; the 23 PR-CRKP strains were divided into 3 main subclusters based on SNP phylogenetic trees, with some aggregation among Clade 2-1 in the isolation department and date. The two-component negative regulatory gene mgrB has seven mutation types including point mutations, different insertion fragments and different insertion positions. Conclusion: The close affinity of PR-CRKP strains indicate the possibility of nosocomial clonal transmission and the need to strengthen surveillance of PR-CRKP strains to prevent epidemic transmission of PR-CRKP.
Humans ; Carbapenems/pharmacology* ; Anti-Bacterial Agents/therapeutic use* ; Klebsiella pneumoniae/genetics* ; Polymyxins/pharmacology* ; beta-Lactamases ; Phylogeny ; Retrospective Studies ; Multilocus Sequence Typing ; Microbial Sensitivity Tests

Objective: The study investigated the clinical distribution, antimicrobial resistance and epidemiologic characteristics of hypervirulent Carbapenem-resistant Klebsiella pneumoniae (hv-CRKP) in a hospital in Henan Province to provide a scientific basis for antibiotic use and nosocomial infection prevention and control. Methods: A retrospective analysis of the clinical data from the cases was carried out in this study. Clinical data of patients infected with the CRKP strain isolated from the clinical microbiology laboratory of Henan Provincial Hospital of Traditional Chinese Medicine from January 2020 to December 2022 were retrospectively analyzed. A string test, virulence gene screening, serum killing, and a G. mellonella infection model were used to screen hv-CRKP isolates. The clinical characteristics of hv-CRKP and the drug resistance rate of hv-CRKP to twenty-five antibiotics were analyzed using WHONET 5.6. Carbapenemase phenotypic characterization of the hv-CRKP was performed by colloidal gold immunochromatographic assay, and Carbapenemase genotyping, multi-locus sequence typing (MLST) and capsular serotyping of hv-CRKP isolates were performed by PCR and Sanger sequencing. Results: A total of non-duplicate 264 CRKP clinical isolates were detected in the hospital from 2020 to 2022, and 23 hv-CRKP isolates were detected, so the corresponding detection rate of hv-CRKP was 8.71% (23/264). The hv-CRKP isolates in this study were mainly from the intensive care unit (10/23) and neurosurgery department (8/23), and the main sources of hv-CRKP isolates were sputum (10/23) and bronchoalveolar lavage fluid (6/23). The hv-CRKP isolates in this study were highly resistant to β-lactam antibiotics, fluoroquinolones and aminoglycosides, and were only susceptible to colistin, tigecycline and ceftazidime/avibactam. The detection rate of the blaKPC-2 among 23 hv-CRKP isolates was 91.30% (21/23) and none of the class B and class D carbapenemases were detected. Results of MLST and capsular serotypes showed that ST11 type hv-CRKP was the dominant strain in the hospital, accounting for 56.52% (13/23), and K64 (9/13) and KL47 (4/13) were the major capsular serotypes. Conclusion: The hv-CRKP isolates from the hospital are mainly from lower respiratory tract specimens from patients admitted to the intensive care department and the drug resistance is relatively severe. The predominant strains with certain polymorphisms are mainly composed of the KPC-2-producing ST11-K64 and ST11-KL47 hv-CRKP isolates in the hospital.
Humans ; Klebsiella pneumoniae/genetics* ; Multilocus Sequence Typing ; Retrospective Studies ; Klebsiella Infections/drug therapy* ; Anti-Bacterial Agents/therapeutic use* ; Hospitals ; Carbapenem-Resistant Enterobacteriaceae/genetics* ; Microbial Sensitivity Tests ; Carbapenems/pharmacology*

Objective: The study investigated the clinical distribution, antimicrobial resistance and epidemiologic characteristics of hypervirulent Carbapenem-resistant Klebsiella pneumoniae (hv-CRKP) in a hospital in Henan Province to provide a scientific basis for antibiotic use and nosocomial infection prevention and control. Methods: A retrospective analysis of the clinical data from the cases was carried out in this study. Clinical data of patients infected with the CRKP strain isolated from the clinical microbiology laboratory of Henan Provincial Hospital of Traditional Chinese Medicine from January 2020 to December 2022 were retrospectively analyzed. A string test, virulence gene screening, serum killing, and a G. mellonella infection model were used to screen hv-CRKP isolates. The clinical characteristics of hv-CRKP and the drug resistance rate of hv-CRKP to twenty-five antibiotics were analyzed using WHONET 5.6. Carbapenemase phenotypic characterization of the hv-CRKP was performed by colloidal gold immunochromatographic assay, and Carbapenemase genotyping, multi-locus sequence typing (MLST) and capsular serotyping of hv-CRKP isolates were performed by PCR and Sanger sequencing. Results: A total of non-duplicate 264 CRKP clinical isolates were detected in the hospital from 2020 to 2022, and 23 hv-CRKP isolates were detected, so the corresponding detection rate of hv-CRKP was 8.71% (23/264). The hv-CRKP isolates in this study were mainly from the intensive care unit (10/23) and neurosurgery department (8/23), and the main sources of hv-CRKP isolates were sputum (10/23) and bronchoalveolar lavage fluid (6/23). The hv-CRKP isolates in this study were highly resistant to β-lactam antibiotics, fluoroquinolones and aminoglycosides, and were only susceptible to colistin, tigecycline and ceftazidime/avibactam. The detection rate of the blaKPC-2 among 23 hv-CRKP isolates was 91.30% (21/23) and none of the class B and class D carbapenemases were detected. Results of MLST and capsular serotypes showed that ST11 type hv-CRKP was the dominant strain in the hospital, accounting for 56.52% (13/23), and K64 (9/13) and KL47 (4/13) were the major capsular serotypes. Conclusion: The hv-CRKP isolates from the hospital are mainly from lower respiratory tract specimens from patients admitted to the intensive care department and the drug resistance is relatively severe. The predominant strains with certain polymorphisms are mainly composed of the KPC-2-producing ST11-K64 and ST11-KL47 hv-CRKP isolates in the hospital.
Humans ; Klebsiella pneumoniae/genetics* ; Multilocus Sequence Typing ; Retrospective Studies ; Klebsiella Infections/drug therapy* ; Anti-Bacterial Agents/therapeutic use* ; Hospitals ; Carbapenem-Resistant Enterobacteriaceae/genetics* ; Microbial Sensitivity Tests ; Carbapenems/pharmacology*

Acinetobacter has been the major pathogen of nosocomial infection. With the wide use of carbapenems, the emergence of multi-resistant isolates especially those resistant to carbapenem, brings a great problem to clinical treatment. The production of inactive enzymes is the main mechanism for antibiotic resistance, particularly the production of carbapenemases mediated by chromosome or plasmid. Combinations of β-lactam antibiotics and sulbactam may show synergism or partial synergism for acinetobacter isolates.
Acinetobacter ; drug effects ; enzymology ; Acinetobacter Infections ; drug therapy ; Anti-Bacterial Agents ; pharmacology ; therapeutic use ; Bacterial Proteins ; metabolism ; Carbapenems ; pharmacology ; therapeutic use ; Drug Resistance, Bacterial ; Microbial Sensitivity Tests ; beta-Lactamases ; metabolism

BACKGROUND: Acinetobacter baumannii infections are difficult to treat owing to the emergence of various antibiotic resistant isolates. Because treatment options are limited for multidrug-resistant (MDR) A. baumannii infection, the discovery of new therapies, including combination therapy, is required. We evaluated the synergistic activity of colistin, doripenem, and tigecycline combinations against extensively drug-resistant (XDR) A. baumannii and MDR A. baumannii. METHODS: Time-kill assays were performed for 41 XDR and 28 MDR clinical isolates of A. baumannii by using colistin, doripenem, and tigecycline combinations. Concentrations representative of clinically achievable levels (colistin 2 microg/mL, doripenem 8 microg/mL) and achievable tissue levels (tigecycline 2 microg/mL) for each antibiotic were used in this study. RESULTS: The colistin-doripenem combination displayed the highest rate of synergy (53.6%) and bactericidal activity (75.4%) in 69 clinical isolates of A. baumannii. Among them, thedoripenem-tigecycline combination showed the lowest rate of synergy (14.5%) and bacteri-cidal activity (24.6%). The doripenem-tigecycline combination showed a higher antagonistic interaction (5.8%) compared with the colistin-tigecycline (1.4%) combination. No antagonism was observed for the colistin-doripenem combination. CONCLUSIONS: The colistin-doripenem combination is supported in vitro by the high rate of synergy and bactericidal activity and lack of antagonistic reaction in XDR and MDR A. baumannii. It seems to be necessary to perform synergy tests to determine the appropri-ate combination therapy considering the antagonistic reaction found in several isolates against the doripenem-tigecycline and colistin-tigecycline combinations. These findings should be further examined in clinical studies.
Acinetobacter Infections/drug therapy/microbiology ; Acinetobacter baumannii/*drug effects/genetics/isolation & purification ; Anti-Bacterial Agents/*pharmacology/therapeutic use ; Bacterial Proteins/genetics ; Carbapenems/*pharmacology/therapeutic use ; Colistin/*pharmacology/therapeutic use ; Drug Resistance, Multiple, Bacterial/*drug effects ; Drug Synergism ; Drug Therapy, Combination ; Humans ; Microbial Sensitivity Tests ; Minocycline/*analogs & derivatives/pharmacology/therapeutic use ; Multilocus Sequence Typing ; beta-Lactamases/genetics

Production of extended-spectrum beta-lactamase (ESBL) is one of the most important resistance mechanisms that hamper the antimicrobial treatment of infections caused by Enterobacteriaceae. ESBLs are classified into several groups according to their amino-acid sequence homology. While TEM and SHV enzymes were the most common ESBLs in the 1990s, CTX-M enzymes have spread rapidly among Enterobacteriaceae in the past decade. In addition, some epidemiological studies showed that organisms producing CTX-M enzymes had become increasingly prevalent in the community setting in certain areas in the world. Several novel enzymes with hydrolyzing activity against oxyimino-cephalosporins, albeit with additional enzymatic characteristics different from those of original TEM and SHV ESBLs (e.g., inhibitor-resistance), have been discovered and pose a problem on the definition of ESBLs. Although several methods to detect the production of ESBL are available in clinical laboratories, existence of other factors contributing resistance against beta-lactams, e.g., inducible production of Amp-C beta-lactamase by some species of Enterobacteriaceae, or inhibitor-resistance in some ESBLs may hinder the detection of ESBLs with these methods. Carbapenems are stable against hydrolyzing activity of ESBLs and are regarded as the drug of choice for the treatment of infections caused by ESBL-producing Enterobacteriaceae. Although several other antimicrobial agents, such as fluoroquinolones and cephamycins, may have some role in the treatment of mild infections due to those organisms, clinical data that warrant the use of antimicrobial agents other than carbapenems in the treatment of serious infections due to those organisms are scarce for now.
Anti-Bacterial Agents/*pharmacology/therapeutic use ; Carbapenems/pharmacology/therapeutic use ; Disk Diffusion Antimicrobial Tests ; Enterobacteriaceae/drug effects/*enzymology/genetics ; Enterobacteriaceae Infections/*drug therapy/microbiology ; Fluoroquinolones/pharmacology/therapeutic use ; Humans ; Microbial Sensitivity Tests/methods ; beta-Lactamases/*biosynthesis/metabolism ; beta-Lactams/*pharmacology/therapeutic use

OBJECTIVETo study the drug resistance of Acinetobacter baumannii (AB) producing VIM-2-type metallo-β-lactamase (MBL) isolated from burn patients of our ward against carbapenem antibiotics and its homology.

METHODSA total of 400 strains of AB (identified) were isolated from sputum, urine, blood, pus, and wound drainage. of burn patients hospitalized in our ward from September 2011 to March 2014. Drug resistance of the 400 strains of AB to 15 antibiotics, including compound sulfamothoxazole, aztreonam, etc. , was tested using the automatic microorganism identifying and drug sensitivity analyzer. Among the carbapenems-resistant AB isolates, modified Hodge test was applied to screen carbapenemase-producing strains. The carbapenemase genes of the carbapenemase-producing strains, and the mobile genetic elements class I-integron (Intl1) gene and conserved sequence (CS) of carbapenemase-producing strains carrying blaVIM-2 gene were determined with PCR and DNA sequencing. For carbapenemase-producing strains carrying blaVIM-2 gene, synergism test with imipenem-ethylene diamine tetraacetic acid (EDTA) and enhancement test with imipenem-EDTA and ceftazidime-EDTA were used to verify the MBL-producing status. Drug resistance of the VIM-2-type MBL-producing AB strains was analyzed. For VIM-2-type MBL-producing AB strains, plasmid conjugation experiment was used to explore the transfer of plasmid; outer membrane protein (OMP) CarO gene was detected by PCR. For VIM-2-type MBL-producing AB strains carrying CarO gene, the protein content of CarO was analyzed with sodium dodecyl sulfate polyacrylamide gel electro- phoresis. The repetitive consensus sequence of Enterobacteriaceae genome PCR (ERIC-PCR) was carried out for gene typing of VIM-2-type MBL-producing AB strains to analyze their homology.

RESULTS(1) The resistant rates of the 400 strains of AB against levofloxacin and compound sulfamethoxazole were low. A total of 381 carbapenems-resistant AB strains were screened, including 240 carbepenemase-producing strains. (2) Out of the 240 carbepenemase-producing strains, 18 strains were found to harbor the blaVIM-2 gene, accounting for 7.5%; 133 strains carried the blaTEM-1 gene, accounting for 55.42%; 195 strains carried the blaOXA23 gene, accounting for 81.25%; 188 strains carried the bla(armA) gene, accounting for 78.33%. (3) Eighteen carbepenemase-producing strains which carried the bla(VIM-2) gene were found to carry the Intl1 gene, showing the Intl1-VIM linkage. Simultaneously, Intl1 variable area CS showed diversity. (4) Eighteen carbepenemase-producing strains which carried the blaVIM-2 gene were verified to produce MBL. The resistant rates of the 18 strains of AB against compound sulfamethoxazole were the lowest, followed by levofloxacin and cefoperazone/sulbactam, and those against the other antibiotics were above 60.00%. (5) Through multiple joint tests, plasmid conjugation experiment positive transfer strain was not found in 18 VIM-2-type MBL-producing AB strains. (6) Nine out of the 18 VIM-2-type MBL-producing AB strains were found to carry CarO gene. The OMP CarO of VIM-2-type MBL-producing AB strains carrying CarO gene was lost or lowered in the protein content. (7) The 18 VIM-2-type MBL-producing AB strains were classified into 6 genotypes by the ERIC-PCR. There were respectively 6, 4, 3, and 1 stain (s) in genotypes A, B, C, and F, and there were 2 strains in genotypes D and E respectively.

CONCLUSIONSThe resistance mechanism of AB against carbapenems is mainly mediated by blaTEM-1, blaOXA-23, and bla(arma); meanwhile, VIM-2-type MBL-producing and lack or change in OMP CarO are attributable to carbapenems resistance of clinically isolated AB from burn wards, and the Intl1 gene may take a part in blaVIM-2 gene transmission.

Acinetobacter baumannii ; drug effects ; enzymology ; genetics ; isolation & purification ; Anti-Bacterial Agents ; pharmacology ; therapeutic use ; Bacterial Proteins ; Burns ; drug therapy ; microbiology ; Carbapenems ; pharmacology ; Drug Resistance, Bacterial ; Genes, Bacterial ; Humans ; Imipenem ; pharmacology ; Microbial Sensitivity Tests ; Sulbactam ; pharmacology ; beta-Lactamases ; genetics

The emergence and spread of carbapenems-resistant Klebsiella pneumoniae (CRKP) in burn ward is an important threat to burn management. CRKP isolates are resistant to almost all available antibiotics and are susceptible only to polymyxins and tigecycline. The mechanism of the drug resistance of CRKP is associated with the plasmid-encoded carbapenemase Klebsiella pneumoniae carbapenemase (KPC), a carbapenem-hydrolyzing β-lactamase. Antibiotics which can currently be used to treat CRKP infection include polymyxins, tigecycline, and some aminoglycosides. The efficacy of using antibiotics in combination is better than that of single-agent therapy for the treatment of CRKP infection in bloodstream. In order to control CRKP infection in burn patients, strategies for preventing CRKP dissemination in burn ward are strongly advocated.
Anti-Bacterial Agents ; therapeutic use ; Bacterial Proteins ; Burns ; drug therapy ; Carbapenems ; pharmacology ; Drug Resistance, Bacterial ; Humans ; Klebsiella Infections ; drug therapy ; microbiology ; prevention & control ; Klebsiella pneumoniae ; drug effects ; Microbial Sensitivity Tests ; Minocycline ; analogs & derivatives ; therapeutic use ; beta-Lactam Resistance ; beta-Lactamases