RESUMEN
Antimicrobial resistance is a global healthcare threat with significant clinical and economic consequences peaking at secondary and tertiary care hospitals where multidrug-resistant Gram-negative bacteria (MDR GNB) lead to poor outcomes. A prospective study was conducted between January and December 2019 for all invasive bloodstream infections (BSIs) secondary to MDR GNB in Qatar identified during routine microbiological service to examine their clinical, microbiological, and genomic characteristics. Out of 3238 episodes of GNB BSIs, the prevalence of MDR GNB was 13% (429/3238). The predominant MDR pathogens were Escherichia coli (62.7%), Klebsiella pneumoniae (20.4%), Salmonella species (6.6%), and Pseudomonas aeruginosa (5.3%), while out of 245 clinically evaluated patients, the majority were adult males, with the elderly constituting almost one-third of the cohort and with highest observed risk for prolonged hospital stays. The risk factors identified included multiple comorbidities, recent healthcare contact, previous antimicrobial therapy, and admission to critical care. The in-hospital mortality rate was recorded at 25.7%, associated with multiple comorbidities, admission to critical care, and the acquisition of MDR Pseudomonas aeruginosa. Resistant pathogens demonstrated high levels of antimicrobial resistance but noticeable susceptibility to amikacin and carbapenems. Genomic analysis revealed that Escherichia coli ST131 and Salmonella enterica ST1 were the predominant clones not observed with other pathogens.
RESUMEN
Background: The global Study of Monitoring Antimicrobial Resistance Trends (SMART) is a surveillance program for evaluation of antimicrobial resistance (AMR) in Gram-negative bacteria (GNB) from different regions including Gulf countries. Objectives: To evaluate AMR in GNB from various clinical specimens including microbiological and genetic characteristics for existing and novel antimicrobials. Methods: A prospective study was conducted on clinical specimens from Hamad Medical Corporation, Qatar, between 2017 and 2019 according to the SMART protocol. Consecutive GNB from different sites were evaluated including lower respiratory, urinary tract, intrabdominal and bloodstream infections. Results: Over the 3 years study period, 748 isolates were evaluated from the specified sites comprising 37 different GNB outlining four key pathogens: Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Stenotrophomonas maltophilia.For the two major pathogens E. coli and K. pneumoniae, phenotypic ESBL was identified in 55.77% (116/208) compared to 39% (73/187), while meropenem resistance was 3.8% compared to 12.8% and imipenem/relebactam resistance was 2.97% compared to 11.76%, respectively. The overall ceftolozane/tazobactam resistance for E. coli was 9.6% (20/208) compared to 14.97% (28/187) for K. pneumoniae while resistance for ceftazidime/avibactam was 3.65% (5/137) and 5.98% (10/117), respectively. Genomic characteristics of 70 Enterobacterales including 48 carbapenem-resistant, revealed prevalence of ß-lactamases from all classes, predominated by blaCXM-15 while carbapenem resistance revealed paucity of blaKPC and dominance of blaOXA-48 and blaNDM resistance genes. Conclusions: Surveillance of GNB from Qatar showed prevalence of key pathogens similar to other regions but demonstrated significant resistance patterns to existing and novel antimicrobials with different underlying resistance mechanisms.
RESUMEN
Objectives: Antimicrobial resistance (AMR) is a global priority with significant clinical and economic consequences. Multidrug-resistant (MDR) Pseudomonas aeruginosa is one of the major pathogens associated with significant morbidity and mortality. In healthcare settings, the evaluation of prevalence, microbiological characteristics, as well as mechanisms of resistance is of paramount importance to overcome associated challenges. Methods: Consecutive clinical specimens of P. aeruginosa were collected prospectively from 5 acute-care and specialized hospitals between October 2014 and September 2017, including microbiological, clinical characteristics and outcomes. Identification and antimicrobial susceptibility test were performed using the BD Phoenix identification and susceptibility testing system, matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS), and minimum inhibitory concentration (MIC) test strips. Overall, 78 selected MDR P. aeruginosa isolates were processed for whole-genome sequencing (WGS). Results: The overall prevalence of MDR P. aeruginosa isolates was 5.9% (525 of 8,892) and showed a decreasing trend; 95% of cases were hospital acquired and 44.8% were from respiratory samples. MDR P. aeruginosa demonstrated >86% resistance to cefepime, ciprofloxacin, meropenem, and piperacillin-tazobactam but 97.5% susceptibility to colistin. WGS revealed 29 different sequence types: 20.5% ST235, 10.3% ST357, 7.7% ST389, and 7.7% ST1284. ST233 was associated with bloodstream infections and increased 30-day mortality. All ST389 isolates were obtained from patients with cystic fibrosis. Encoded exotoxin genes were detected in 96.2% of isolates. Conclusions: MDR P. aeruginosa isolated from clinical specimens from Qatar has significant resistance to most agents, with a decreasing trend that should be explored further. Genomic analysis revealed the dominance of 5 main clonal clusters associated with mortality and bloodstream infections. Microbiological and genomic monitoring of MDR P. aeruginosa has enhanced our understanding of AMR in Qatar.
RESUMEN
Objectives: Extended-spectrum -lactamases (ESBLs) mechanism of resistance in Enterobacterales leads to poor clinical outcomes. Ceftazidime/avibactam and ceftolozane/tazobactam are two broad-spectrum antimicrobial combinations that are effective against multidrug-resistant organisms with regional variations. This study aims to evaluate the antimicrobial susceptibility test (AST) for both combinations against ESBL-producing Enterobacterales isolated from intensive care units (ICUs) in tertiary hospitals from November 2012 to October 2013 in Qatar. Methods: A total of 629 Enterobacterales isolates from ICUs were screened for ESBL production using BD-PhoenixTM confirmed by double-disk potentiation, while ESBL-genes were detected by polymerase chain reaction. The ASTs for ceftazidime/avibactam and ceftolozane/tazobactam were assessed by minimum inhibitory concentration (MIC) test strips. A single isolate that was resistant to both combinations was subjected to whole-genome sequencing. Results: The prevalence of ESBL-producing Enterobacterales isolated from ICUs was 17.3% (109/629) with predominance of Klebsiella pneumoniae (56/109; 51.4%) and Escherichia coli (38/109; 34.9%). The susceptibility of ceftazidime/avibactam and ceftolozane/tazobactam against ESBL-producers was 99.1% (108/109) and most (81/109; 74.3%) had MICs < 0.5 for both combinations. The predominant ESBL-gene was blaCTX-M (72/109; 66.1%). A single isolate that was resistant to both combinations harbored multiple ESBL resistant-genes including blaVEB-5 and blaVIM-2. Conclusions: ESBL-producing Enterobacterales isolated from ICUs were predominantly K. pneumoniae and E. coli, mainly harboring blaCTX-M gene. They were highly susceptible to ceftazidime/avibactam and ceftolozane/tazobactam suggesting potential alternatives to currently available therapeutic options.
RESUMEN
Ceftazidime-avibactam and ceftolozane-tazobactam are approved for the treatment of complicated Gram-negative bacterial infections including multidrug-resistant (MDR) Pseudomonas aeruginosa. Resistance to both agents has been reported, but the underlying mechanisms have not been fully explored. This study aimed to correlate ß-lactamases with phenotypic resistance to ceftazidime-avibactam and/or ceftolozane-tazobactam in MDR-P. aeruginosa from Qatar. A total of 525 MDR-P. aeruginosa isolates were collected from clinical specimens between 2014 and 2017. Identification and antimicrobial susceptibility were performed by the BD PhoenixTM system and gradient MIC test strips. Of the 75 sequenced MDR isolates, 35 (47%) were considered as having difficult-to-treat resistance, and 42 were resistant to ceftazidime-avibactam (37, 49.3%), and/or ceftolozane-tazobactam (40, 53.3%). They belonged to 12 sequence types, with ST235 being predominant (38%). Most isolates (97.6%) carried one or more ß-lactamase genes, with blaOXA-488 (19%) and blaVEB-9 (45.2%) being predominant. A strong association was detected between class B ß-lactamase genes and both ceftazidime-avibactam and ceftolozane-tazobactam resistance, while class A genes were associated with ceftolozane-tazobactam resistance. Co-resistance to ceftazidime-avibactam and ceftolozane-tazobactam correlated with the presence of blaVEB-9, blaPDC-35, blaVIM-2, blaOXA-10 and blaOXA-488. MDR-P. aeruginosa isolates resistant to both combination drugs were associated with class B ß-lactamases (blaVIM-2) and class D ß-lactamases (blaOXA-10), while ceftolozane-tazobactam resistance was associated with class A (blaVEB-9), class C (blaVPDC-35), and class D ß-lactamases (blaOXA-488).
RESUMEN
BACKGROUND: Bloodstream infections (BSIs) caused by multidrug-resistant (MDR)-Pseudomonas aeruginosa are associated with poor clinical outcomes, at least partly due to delayed appropriate antimicrobial therapy. The characteristics of MDR-P. aeruginosa bloodstream isolates have not been evaluated in Qatar. Our study aimed to examine in vitro susceptibility, clinical and molecular characteristics, and mechanisms of resistance of MDR-P. aeruginosa bloodstream isolates from Qatar. MATERIALS AND METHODS: We included all MDR-P. aeruginosa isolated from blood cultures taken between October 2014 and September 2017. Blood cultures were processed using BD BACTEC™ FX automated system. BD Phoenix™ was used for identification, Liofilchem® MIC Test Strips for MIC determination. Whole-genome sequencing was performed using the Illumina-HiSeq-2000. RESULTS: Out of 362 P. aeruginosa bloodstream isolates, 16 (4.4%) were MDR. The median patient age was 55 years (range 43-81) and all patients presented with septic shock. Most patients received meropenem (12/16) and/or colistin (10/16). Clinical response was achieved in eight patients, and five patients died within 30-days. MDR-P. aeruginosa isolates belonged to 13 different sequence types. All isolates were non-susceptible to cefepime and ciprofloxacin. The most active agents were colistin (16/16) and aztreonam (10/16). Seven isolates produced blaVIM, and four possessed genes encoding extended-spectrum ß-lactamases. Aminoglycoside modifying enzymes were present in 15/16, transferable qnr-mediated quinolone resistance gene was detected in 3/16, and the novel ciprofloxacin modifying enzyme CrpP-encoding gene in one isolate. CONCLUSION: MDR-P. aeruginosa BSIs are relatively uncommon in Qatar but are highly resistant, harbour multiple resistance genes, and are commonly associated with unfavourable clinical outcomes. Colistin was the only agent with consistent activity against the study isolates.Key messagesMDR-P. aeruginosa constituted <5% of P. aeruginosa blood isolates over three years.Typical risk factors for MDR infections were highly prevalent in the study population and overall clinical outcomes are consistent with those previously reported.Colistin was the only agent with consistent antibacterial activity against the study isolates.
Asunto(s)
Infecciones por Pseudomonas , Sepsis , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Farmacorresistencia Bacteriana Múltiple/genética , Humanos , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Epidemiología Molecular , Infecciones por Pseudomonas/tratamiento farmacológico , Infecciones por Pseudomonas/epidemiología , Infecciones por Pseudomonas/microbiología , Pseudomonas aeruginosa/genética , Qatar/epidemiología , Sepsis/tratamiento farmacológico , Sepsis/epidemiologíaRESUMEN
BACKGROUND: The distribution of ß-lactam resistance genes in P. aeruginosa is often closely related to the distribution of certain high-risk international clones. We used whole-genome sequencing (WGS) to identify the predominant sequence types (ST) and ß-lactamase genes in clinical isolates of multidrug-resistant (MDR)-P. aeruginosa from Qatar METHODS: Microbiological identification and susceptibility tests were performed by automated BD Phoenix™ system and manual Liofilchem MIC Test Strips. RESULTS: Among 75 MDR-P. aeruginosa isolates; the largest proportions of susceptibility were to ceftazidime-avibactam (n = 36, 48%), followed by ceftolozane-tazobactam (30, 40%), ceftazidime (n = 21, 28%) and aztreonam (n = 16, 21.3%). All isolates possessed Class C and/or Class D ß-lactamases (n = 72, 96% each), while metallo-ß-lactamases were detected in 20 (26.7%) isolates. Eight (40%) metallo-ß-lactamase producers were susceptible to aztreonam and did not produce any concomitant extended-spectrum ß-lactamases. High risk ST235 (n = 16, 21.3%), ST357 (n = 8, 10.7%), ST389 and ST1284 (6, 8% each) were most frequent. Nearly all ST235 isolates (15/16; 93.8%) were resistant to all tested ß-lactams. CONCLUSION: MDR-P. aeruginosa isolates from Qatar are highly resistant to antipseudomonal ß-lactams. High-risk STs are predominant in Qatar and their associated MDR phenotypes are a cause for considerable concern.
Asunto(s)
Antibacterianos/farmacología , Pseudomonas aeruginosa/efectos de los fármacos , beta-Lactamasas/fisiología , Farmacorresistencia Bacteriana Múltiple , Pruebas de Sensibilidad Microbiana , Pseudomonas aeruginosa/enzimología , Pseudomonas aeruginosa/genética , Secuenciación Completa del Genoma , beta-Lactamasas/genéticaRESUMEN
BACKGROUND: The excessive and inappropriate use of antibiotics is universal across all healthcare facilities. In Qatar there has been a substantial increase in antimicrobial consumption coupled with a significant rise in antimicrobial resistance (AMR). Antimicrobial stewardship programmes (ASPs) have become a standard intervention for effective optimization of antimicrobial prescribing. METHODS: A before-after study was conducted in Hamad General Hospital (603 bed acute care hospital): 1 year before implementation of a comprehensive ASP compared with the following 2 years. The ASP included a hospital-wide pre-authorization requirement by infectious diseases physicians for all broad-spectrum antibiotics. Prevalence of MDR Pseudomonas aeruginosa was compared with antimicrobial consumption, calculated as DDD per 1000 patient-days (DDD/1000 PD). Susceptibility was determined using broth microdilution, as per CLSI guidelines. Antibiotic use was restricted through the ASP, as defined in the hospital's antibiotic policy. RESULTS: A total of 6501 clinical isolates of P. aeruginosa were collected prospectively over 3 years (2014-17). Susceptibility to certain antimicrobials improved after the ASP was implemented in August 2015. The prevalence of MDR P. aeruginosa showed a sustained decrease from 2014 (9%) to 2017 (5.46%) (P = 0.019). There was a significant 23.9% reduction in studied antimicrobial consumption following ASP implementation (P = 0.008). The yearly consumption of meropenem significantly decreased from 47.32 to 31.90 DDD/1000 PD (P = 0.012), piperacillin/tazobactam from 45.35 to 32.67 DDD/1000 PD (P < 0.001) and ciprofloxacin from 9.71 to 5.63 DDD/1000 PD (P = 0.015) (from 2014 to 2017). CONCLUSIONS: The successful implementation of the ASP led to a significant reduction in rates of MDR P. aeruginosa, pointing towards the efficacy of the ASP in reducing AMR.
RESUMEN
OBJECTIVES: To investigate the in vitro activity of ceftazidime/avibactam and ceftolozane/tazobactam against clinical isolates of MDR Pseudomonas aeruginosa from Qatar, as well as the mechanisms of resistance. METHODS: MDR P. aeruginosa isolated between October 2014 and September 2015 from all public hospitals in Qatar were included. The BD PhoenixTM system was used for identification and initial antimicrobial susceptibility testing, while Liofilchem MIC Test Strips (Liofilchem, Roseto degli Abruzzi, Italy) were used for confirmation of ceftazidime/avibactam and ceftolozane/tazobactam susceptibility. Ten ceftazidime/avibactam- and/or ceftolozane/tazobactam-resistant isolates were randomly selected for WGS. RESULTS: A total of 205 MDR P. aeruginosa isolates were included. Of these, 141 (68.8%) were susceptible to ceftazidime/avibactam, 129 (62.9%) were susceptible to ceftolozane/tazobactam, 121 (59.0%) were susceptible to both and 56 (27.3%) were susceptible to neither. Twenty (9.8%) isolates were susceptible to ceftazidime/avibactam but not to ceftolozane/tazobactam and only 8 (3.9%) were susceptible to ceftolozane/tazobactam but not to ceftazidime/avibactam. Less than 50% of XDR isolates were susceptible to ceftazidime/avibactam or ceftolozane/tazobactam. The 10 sequenced isolates belonged to six different STs and all produced AmpC and OXA enzymes; 5 (50%) produced ESBL and 4 (40%) produced VIM enzymes. CONCLUSIONS: MDR P. aeruginosa susceptibility rates to ceftazidime/avibactam and ceftolozane/tazobactam were higher than those to all existing antipseudomonal agents, except colistin, but were less than 50% in extremely resistant isolates. Non-susceptibility to ceftazidime/avibactam and ceftolozane/tazobactam was largely due to the production of ESBL and VIM enzymes. Ceftazidime/avibactam and ceftolozane/tazobactam are possible options for some patients with MDR P. aeruginosa in Qatar.
Asunto(s)
Antibacterianos/farmacología , Compuestos de Azabiciclo/farmacología , Ceftazidima/farmacología , Cefalosporinas/farmacología , Farmacorresistencia Bacteriana Múltiple , Pseudomonas aeruginosa/efectos de los fármacos , Tazobactam/farmacología , Combinación de Medicamentos , Humanos , Pruebas de Sensibilidad Microbiana , Estudios Prospectivos , Infecciones por Pseudomonas/microbiología , Pseudomonas aeruginosa/genética , Qatar , Secuenciación Completa del GenomaRESUMEN
INTRODUCTION: Multidrug-resistant Pseudomonas aeruginosa (MDR-PA) is an important and growing issue in the care of patients with cystic fibrosis (CF), and a major cause of morbidity and mortality. OBJECTIVE: The objective of the study was to describe the frequency of MDR-PA recovered from the lower respiratory samples of pediatric and adult CF patients, and its antibiotic resistance pattern to commonly used antimicrobial agents including ß-lactams, aminoglycosides, and fluoroquinolones. MATERIALS AND METHODS: The lower respiratory isolates of P. aeruginosa were obtained from inpatients and outpatients CF clinics from a tertiary care teaching hospital for the period from October 2014 to September 2015. The identification and antimicrobial susceptibility for all the isolates were performed by using the BD Phoenix™ and E-test in compliance with Clinical and Laboratory Standards Institute (CLSI) guidelines. RESULTS: A total of 61 P. aeruginosa samples were isolated from thirty CF patients from twenty families. Twelve sputum samples were positive for MDR-PA (seven nonmucoid and five mucoid isolates) from five CF patients (five families) with moderate-to-very severe lung disease given MDR-PA frequency of 19.7%. The median age of the study group was 20 (range 10-30) years. Three CF patients were on chronic inhaled tobramycin and two on nebulized colistin. The antimicrobial patterns of isolates MDR-PA showed the highest rate of resistance toward each gentamycin, amikacin, and cefepime (100%), followed by 91.7% to ciprofloxacin, 75% to tobramycin, 58.3% to meropenem, and 50% to piperacillin-tazobactam. None of the isolates were resistant to colistin during the study period. CONCLUSION: The study results emphasize that the emergence of a significant problem in the clinical isolates of P. aeruginosa in CF patients that dictate appropriate attention to the antibiotic management after proper surveillance.
RESUMEN
INTRODUCTION: Early identification of microbial organisms from respiratory secretions of patients with cystic fibrosis (CF) is important to guide therapeutic decisions. The objective was to compare the accuracy of matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) relative to the conventional phenotypic method in identifying common bacterial isolates, including nonfermenting Gram-negative bacteria, in a cohort of patients with CF. METHODS: A total of 123 isolates from 50 patients with CF representing 14 bacterial species from respiratory specimens were identified using MALDI-TOF MS in parallel with conventional phenotypic methods. Discrepancies were confirmed by 16S ribosomal RNA (rRNA) gene sequencing in five Gram-negative isolates. RESULTS: The MALDI-TOF MS managed to identify 122/123 (99.2%) bacterial isolates to the genus level and 118/123 (95.9%) were identified to the species level. The MALDI-TOF MS results were 100% consistent to the species level with conventional phenotypic identification for isolates of Staphylococcus aureus, Pseudomonas aeruginosa, Haemophilus influenzae, Streptococcus pyogenes, Achromobacter xylosoxidans, Stenotrophomonas maltophilia, and other uncommon organisms such as Chryseobacterium gleum and Enterobacter cloacae. The 5/123 (4.6%) isolates misidentified were all Gram-negative bacteria. The isolation of E. cloacae and Haemophilus paraphrohaemolyticus may extend the potentially pathogenic list of organisms isolated from patients with CF. CONCLUSION: Although the technique provides an early identification and antimicrobial therapy approach in patients with CF, limitation in the diagnosis of uncommon Gram-negative bacteria may exist.