A 7-Year Brazilian National Perspective on Plasmid-Mediated Carbapenem Resistance in Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii Complex and the Impact of the Coronavirus Disease 2019 Pandemic on Their Occurrence.

BACKGROUND: Carbapenemase production is a global public health threat. Antimicrobial resistance (AMR) data analysis is critical to public health policy. Here we analyzed carbapenemase detection trends using the AMR Brazilian Surveillance Network. METHODS: Carbapenemase detection data from Brazilian hospitals included in the public laboratory information system dataset were evaluated. The detection rate (DR) was defined as carbapenemase detected by gene tested per isolate per year. The temporal trends were estimated using the Prais-Winsten regression model. The impact of COVID-19 on carbapenemase genes in Brazil was determined for the period 2015-2022. Detection pre- (October 2017 to March 2020) and post-pandemic onset (April 2020 to September 2022) was compared using the χ2 test. Analyses were performed with Stata 17.0 (StataCorp, College Station, TX). RESULTS: 83 282 blaKPC and 86 038 blaNDM were tested for all microorganisms. Enterobacterales DR for blaKPC and blaNDM was 68.6% (41 301/60 205) and 14.4% (8377/58 172), respectively. P. aeruginosa DR for blaNDM was 2.5% (313/12 528). An annual percent increase for blaNDM of 41.1% was observed, and a decrease for blaKPC of -4.0% in Enterobacterales, and an annual increase for blaNDM of 71.6% and for blaKPC of 22.2% in P. aeruginosa. From 2020 to 2022, overall increases of 65.2% for Enterobacterales, 77.7% for ABC, and 61.3% for P. aeruginosa were observed in the total isolates. CONCLUSIONS: This study shows the strengths of the AMR Brazilian Surveillance Network with robust data related to carbapenemases in Brazil and the impact of COVID-19 with a change in carbapenemase profiles with blaNDM rising over the years.

Non-clonal occurrence of pmrB mutations associated with polymyxin resistance in carbapenem-resistant Klebsiella pneumoniae in Brazil.

BACKGROUND: Polymyxins are currently used as a "last-line" treatment for multidrug-resistant Gram-negative infections. OBJECTIVES: To identify the major mechanisms of resistance to polymyxin and compare the genetic similarity between multi-drug resistant Klebsiella pneumoniae strains recovered from inpatients of public hospitals in the Mid-West of Brazil. METHODS: 97 carbapenems non-susceptible K. pneumoniae were studied. ß-lactamases (bla OXA-48, bla KPC, bla NDM, bla CTX-M, bla SHV, bla TEM, bla IMP, bla VIM) and mcr-1 to mcr-5 genes were investigated by polymerase chain reaction (PCR). Mutations in chromosomal genes (pmrA, pmrB, phoP, phoQ, and mgrB) were screened by PCR and DNA sequencing. Clonal relatedness was established by using pulsed-field gel electrophoresis and multilocus sequence typing. FINDINGS: K. pneumoniae isolates harbored bla KPC (93.3%), bla SHV (86.6%), bla TEM (80.0%), bla CTX-M (60%) genes. Of 15 K. pneumoniae resistant to polymyxin B the authors identified deleterious mutations in pmrB gene, mainly in T157P. None K. pneumoniae presented mcr gene variants. Genetic polymorphism analyses revealed 12 different pulsotypes. MAIN CONCLUSIONS: Deleterious mutations in pmrB gene is the main chromosomal target for induction of polymyxin resistance in carbapenem-resistant K. pneumoniae in public hospitals in the Mid-West of Brazil.

Molecular Epidemiology of blaKPC-Encoding Klebsiella pneumoniae Isolated from Public Hospitals in Midwest of Brazil.

This study was conducted to determine the molecular epidemiology of blaKPC-encoding Klebsiella pneumoniae recovered from three public hospitals in Brazil. Molecular investigation of blaOXA-48, blaKPC, blaNDM, blaCTX-M, blaSHV, blaTEM, blaIMP, and blaVIM resistance genes was performed in 99 K. pneumoniae isolates from inpatients of intensive care units. Antimicrobial susceptibility was determined with a Vitek-2 System, except for polymyxin B, which was evaluated by the microbroth dilution test. Clonal relatedness was established by pulsed-field gel electrophoresis and multilocus sequence typing. Screening resistance genes showed that K. pneumoniae isolates carried the blaKPC (88.9%), blaSHV (73.5%), blaTEM (72.2%), and blaCTX-M (43.9%) genes. The most frequent sequence types (STs) were ST273, ST11, ST 1298, ST13, ST2687, and ST37. We report new STs in K. pneumoniae that have not been detected previously in Brazil. K. pneumoniae belonging to the same clone is present in different hospitals in the same region, showing the spread of multidrug-resistant K. pneumoniae.

Post-neurosurgical meningitis caused by KPC-producing Klebsiella pneumoniae: report of two cases.

Nosocomial bacterial infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) is associated with high mortality in neurosurgical patients. There are few reports in the literature on meningitis caused by CRKP. We report two cases of CRKP meningitis after neurosurgery. The K. pneumoniae identification and antimicrobial susceptibility testing were performed using the Vitek Compact System. Minimum inhibitory concentrations of polymyxin B were determined using the broth microdilution method. Molecular typing of K. pneumoniae isolates was investigated using multilocus sequence typing. Antimicrobial susceptibility testing showed that the K. pneumoniae isolates were multidrug resistant and co-produced extended-spectrum ß-lactamases and KPC enzymes. The patients were treated with intrathecal polymyxin. Genetic polymorphism analyses revealed two different K. pneumoniae clones (ST1298 and ST2687), which were observed for the first time in CRKP infections. We recommend intravenous administration of intrathecal polymyxin for treating meningitis caused by multidrug-resistant K. pneumoniae .

Melioidosis, an emerging infectious disease in the Midwest Brazil: A case report.

RATIONALE: Melioidosis is an emerging infectious disease in Brazil and caused by Burkholderia pseudomallei, with high morbidity and mortality rates. A total of 28 melioidosis cases were reported in Brazil until 2015. The majority of melioidosis cases were reported in the Northwest region of Brazil and such cases were not previously detected in the Midwest region of Brazil. PATIENT CONCERNS: A 42-year-old man was admitted with a non-productive cough, dyspnea, myalgia, diffuse abdominal pain. Pulmonary auscultation revealed a vesicular murmur, snoring sounds, and the presence of basal crackling rales in the left hemithorax. The patient evolved with several respiratory failures and he was diagnosed as the first case of community-acquired pneumonia with sepsis caused by B pseudomallei in Mato Grosso do Sul, Midwest state of Brazil. DIAGNOSIS: The cell isolates were subjected to 16S rRNA gene sequencing to confirm the bacterial species. INTERVENTIONS: Administration of trimethoprim/sulfamethoxazole and meropenem stabilized the clinical condition of the patient. Subsequently upon discharge, the patient was also treated with trimethoprim/sulfametothoxazole for a year. OUTCOME: We reported the first case of community-acquired pneumonia with sepsis caused by B pseudomallei in Mato Grosso do Sul, Midwest state of Brazil and the patient survived. LESSONS: The emergence of melioidosis in the Midwest region is being neglected and underestimated and melioidosis must be considered of the differential diagnosis in community infections.

Non-clonal occurrence of pmrB mutations associated with polymyxin resistance in carbapenem-resistant Klebsiella pneumoniae in Brazil

BACKGROUND Polymyxins are currently used as a "last-line" treatment for multidrug-resistant Gram-negative infections. OBJECTIVES To identify the major mechanisms of resistance to polymyxin and compare the genetic similarity between multi-drug resistant Klebsiella pneumoniae strains recovered from inpatients of public hospitals in the Mid-West of Brazil. METHODS 97 carbapenems non-susceptible K. pneumoniae were studied. β-lactamases (bla OXA-48, bla KPC, bla NDM, bla CTX-M, bla SHV, bla TEM, bla IMP, bla VIM) and mcr-1 to mcr-5 genes were investigated by polymerase chain reaction (PCR). Mutations in chromosomal genes (pmrA, pmrB, phoP, phoQ, and mgrB) were screened by PCR and DNA sequencing. Clonal relatedness was established by using pulsed-field gel electrophoresis and multilocus sequence typing. FINDINGS K. pneumoniae isolates harbored bla KPC (93.3%), bla SHV (86.6%), bla TEM (80.0%), bla CTX-M (60%) genes. Of 15 K. pneumoniae resistant to polymyxin B the authors identified deleterious mutations in pmrB gene, mainly in T157P. None K. pneumoniae presented mcr gene variants. Genetic polymorphism analyses revealed 12 different pulsotypes. MAIN CONCLUSIONS Deleterious mutations in pmrB gene is the main chromosomal target for induction of polymyxin resistance in carbapenem-resistant K. pneumoniae in public hospitals in the Mid-West of Brazil.