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1.
Int J Antimicrob Agents ; 55(3): 105891, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31923569

RESUMO

Ceftolozane/tazobactam (C/T) is a novel ß-lactam/ß-lactamase inhibitor combination targeting Enterobacteriaceae and Pseudomonas aeruginosa (PA). It is approved in adult patients for complicated urinary tract infections (cUTIs) and complicated intra-abdominal infections (cIAIs) as well as for nosocomial pneumonia. It displays excellent activity against PA, even multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains. The aim of this systematic review (PROSPERO protocol no. CRD42019117350) was to summarise the available evidence from observational studies regarding the efficacy and safety of off-label use of C/T when administered to treat MDR- or XDR-PA infections. The MEDLINE and Embase databases were screened from inception up to 30 June 2019. Studies were deemed eligible if they described real-life use of C/T in the case of MDR- or XDR-PA infections for non-approved indications. Exclusion criteria were cIAIs, cUTIs, pneumonia (unless occurring in a paediatric population) and infections by non-MDR/XDR-PA. Thirty articles fulfilled the inclusion criteria. In total, 130 cases of MDR- or XDR-PA infections treated with C/T in 128 patients were described. The most relevant off-label uses were skin and soft-tissue infection (49/30; 37.7%), bone and joint infection (42/130; 32.3%) and bloodstream infection (23/130; 17.7%). Five cases involved paediatric patients. The overall clinical success rate was 76.2%. The most common adverse event was hypokalaemia (4.2%, in 48 evaluable cases). C/T may be a useful therapeutic option for difficult-to-treat infections by PA even outside the framework of approved indications. Further studies are necessary to better define new indications for the drug.


Assuntos
Antibacterianos/uso terapêutico , Cefalosporinas/uso terapêutico , Infecções por Enterobacteriaceae/tratamento farmacológico , Enterobacteriaceae/efeitos dos fármacos , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/efeitos dos fármacos , Tazobactam/uso terapêutico , Antibacterianos/farmacologia , Cefalosporinas/farmacologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Humanos , Infecções Intra-Abdominais/tratamento farmacológico , Estudos Observacionais como Assunto , Infecções dos Tecidos Moles/tratamento farmacológico , Tazobactam/farmacologia , Infecções Urinárias/tratamento farmacológico
2.
Int J Antimicrob Agents ; 55(3): 105887, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31926283

RESUMO

The STEP surveillance study was designed to increase knowledge about distribution of multidrug-resistant (MDR) Enterobacterales and Pseudomonas aeruginosa in Portugal, focusing on the intensive care unit (ICU). Antimicrobial susceptibility of common agents was also evaluated and compared with that of one of the latest therapeutic introductions, ceftolozane-tazobactam (C/T). Clinical isolates of Enterobacterales (n=426) and P. aeruginosa (n=396) from patients admitted in Portuguese ICUs were included. Activity of C/T and comparators was investigated using standard broth microdilution. Isolates were recovered from urinary tract (UTI, 36.9%), intra-abdominal (IAI, 24.2%) and lower respiratory tract (LRTI, 38.9%) infections. In P. aeruginosa, overall distribution of MDR/extremely-drug resistant (XDR)/pan-drug resistant (PDR) isolates accounted for 21.2%, 23.2% and 0.8%, respectively. C/T was the most potent agent tested against P. aeruginosa and MDR/XDR/PDR phenotypes. In Escherichia coli, extended-spectrum beta-lactamases (ESBL) and carbapenemase (CP) phenotypes accounted for 16.6% and 1.7%, respectively, whereas in Klebsiella spp., ESBL and CP-phenotypes represented 28.5% and 17.9%, respectively. Overall, susceptibility of C/T against Enterobacterales was 86.9%. C/T was the least affected agent in E. coli (99.4% susceptibility), whereas its activity was moderate in Klebsiella spp. (71.5%) and Enterobacter spp. (70.4%), due in part to a high rate of ESBL and CP-phenotypes. In Enterobacterales, blaKPC was the most prevalent CP gene (63.0%), followed by blaOXA-48 (33.3%) and blaVIM (3.7%). These microbiological results reinforce C/T as a therapeutic option in ICU patients with UTI, IAI or LRTI due to P. aeruginosa or Enterobacterales isolates, but not for CP producers.


Assuntos
Antibacterianos/farmacologia , Cefalosporinas/farmacologia , Infecções por Enterobacteriaceae/tratamento farmacológico , Enterobacteriaceae/efeitos dos fármacos , Infecções Intra-Abdominais/tratamento farmacológico , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/efeitos dos fármacos , Infecções Respiratórias/tratamento farmacológico , Tazobactam/farmacologia , Infecções Urinárias/tratamento farmacológico , Antibacterianos/uso terapêutico , Cefalosporinas/uso terapêutico , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Infecções por Enterobacteriaceae/microbiologia , Humanos , Unidades de Terapia Intensiva , Portugal , Infecções por Pseudomonas/microbiologia , Tazobactam/uso terapêutico
3.
Int J Antimicrob Agents ; 55(3): 105905, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31991221

RESUMO

BACKGROUND: Limited treatment options complicate management of infections with New Delhi metallo-ß-lactamase (NDM)-producing organisms. The efficacy of combination therapy with meropenem (MEM) and cefmetazole (CMZ) was assessed against NDM-producing Enterobacteriaceae. MATERIALS AND METHODS: Twelve Escherichia coli clinical isolates harbouring blaNDM-1 and a positive control E. coli BAA-2469 harbouring blaNDM-1 were studied. Minimum inhibitory concentrations (MICs) of MEM, ertapenem (ERT) and CMZ were determined by broth microdilution. Checkerboard and time-kill assays were performed to confirm the in vitro efficacy of the MEM/CMZ combination. Scanning electron microscopy, kinetic studies and whole-genome sequence analysis were used to determine the antimicrobial resistance mechanisms. RESULTS: MICs of MEM, ERT and CMZ in monotherapy ranged from 8 to 32, 16 to 128, and 32 to 512 µg/mL, respectively. In the checkerboard assay, MEM/ERT resulted in no synergy, whereas MEM/CMZ showed a synergistic effect in all the tested isolates. Furthermore, the MIC of MEM in combination decreased by 2- to 8-fold compared with that of MEM alone. The time-kill study revealed a bactericidal effect in 4 of 13 isolates at 24 h. Scanning electron microscopy showed spheroidisation of the bacterial cell in the MEM/CMZ combination; this was not observed in single antibiotic conditions. Kinetic studies indicated CMZ was a better antagonist for NDM-1 than ERT. Whole-genome sequence analysis did not reveal any explainable differences between isolates susceptible and those non-susceptible to combination therapy. CONCLUSION: In vitro studies showed the potential effectiveness of MEM/CMZ combination therapy against NDM-producing organisms.


Assuntos
Antibacterianos/farmacologia , Cefmetazol/farmacologia , Infecções por Enterobacteriaceae/tratamento farmacológico , Enterobacteriaceae/efeitos dos fármacos , Meropeném/farmacologia , Antibacterianos/uso terapêutico , Cefmetazol/uso terapêutico , Quimioterapia Combinada , Enterobacteriaceae/metabolismo , Infecções por Enterobacteriaceae/microbiologia , Ertapenem/farmacologia , Humanos , Meropeném/uso terapêutico , beta-Lactamases/biossíntese
4.
Medicine (Baltimore) ; 98(39): e17339, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574872

RESUMO

INTRODUCTION: During the past decade, the rate of carbapenem resistance among Enterobacteriaceae, mostly in Escherichia coli and Klebsiella pneumoniae, has significantly increased worldwide. It is a great challenge for the choice of drug treatment especially in children.Tigecycline is the first drug in the glycylcycline class of antibiotics. For children, the China Food and Drug Administration and US Food and Drug Administration postulated that tigecycline is not recommended. It must be used only as salvage therapy for life-threatening infections in critically ill children who have no alternative treatment options. PATIENT CONCERNS: A male pediatric case of 4.5 months was blood stream infection after liver transplantation. The blood cultures obtained grew Gram-negative rods, which reportedly grew a strain of extended-spectrum ß-lactamase and carbapenemases-producing Escherichia coli within 10 hours. All bacterial isolates were found to be resistant to all antimicrobial agents except aminoglycosides and tigecycline. DIAGNOSES: Complicated intra-abdominal infection, central line-associated blood stream infection. INTERVENTIONS: The blood stream infection with carbapenem-resistant Escherichia coli after liver transplantation was cured by tigecycline. OUTCOMES: The patient's condition continued to improve, then transferred to general ward. CONCLUSION: The following report, to our knowledge, is the youngest liver transplantation patient who used tigecycline treatment around the world. It provides reference and experience for the use of tigecycline in infants with severe infections.


Assuntos
Antibacterianos/uso terapêutico , Enterobacteriáceas Resistentes a Carbapenêmicos , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Escherichia coli/tratamento farmacológico , Complicações Pós-Operatórias/tratamento farmacológico , Tigeciclina/uso terapêutico , Infecções por Enterobacteriaceae/microbiologia , Infecções por Escherichia coli/microbiologia , Humanos , Lactente , Transplante de Fígado/efeitos adversos , Masculino , Complicações Pós-Operatórias/microbiologia
5.
BMC Infect Dis ; 19(1): 772, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31484510

RESUMO

BACKGROUND: Carbapenem-resistant Enterobacteriaceae (CRE) represent an important global threat. The aim of this study is to describe the clinical course and outcomes of patients with CRE infections treated with ceftazidime-avibactam (CAZ-AVI) compared to patients treated with other agents. METHODS: A retrospective cohort study of patients with established CRE infections from January 2017 until August 2018 was conducted. All patients who received CAZ-AVI and all cultures with carbapenem-resistant isolates were screened. We compared patients who received CAZ-AVI for CRE infections with patients who received other agents. RESULTS: A total of 38 consecutive patients with CRE infections were identified. Age and baseline comorbidities were similar between the two groups. The median time from admission to isolation of CRE culture was 22.5 days in the CAZ-AVI group and 17 days in the comparative group (P = 0.7). The incidence of CRE bacteremia was similar between the two groups: 7 patients (70%) in the CAZ-AVI group and 15 patients (53.6%) in the comparative group (P = 0.47). The most common type of CRE infections in both groups was hospital acquired pneumonia (HAP). Klebsiella pneumoniae was the predominant pathogen in both groups. A carbapenemase gene was detected in 35 (92%) patients; the OXA-48 gene was the predominant gene identified in 28 (74%) isolates. Eight out of ten patients in the CAZ-AVI group and fifteen out of twenty-eight in the comparative group achieved clinical remission (P = 0.14). After thirty days, all-cause mortality was observed in five patients in the CAZ-AVI group and 16 patients in the comparative group, accounting for 50 and 57% respectively. CONCLUSIONS: In patients with established OXA-48-type CRE infection, CAZ-AVI is a reasonable alternative to standard therapy. These findings need to be confirmed in prospective studies.


Assuntos
Compostos Azabicíclicos/uso terapêutico , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Ceftazidima/uso terapêutico , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Infecções por Enterobacteriaceae/tratamento farmacológico , Adulto , Idoso , Antibacterianos/uso terapêutico , Enterobacteriáceas Resistentes a Carbapenêmicos/fisiologia , Combinação de Medicamentos , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Estudos Retrospectivos
6.
Drugs ; 79(14): 1529-1541, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31407238

RESUMO

Extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae are a major global public health concern. Presently, Escherichia coli with CTX-Ms are the most common species associated with global ESBLs; CTX-M-15 is the most frequent CTX-M worldwide and is followed by CTX-M-14, which is often found in South-East Asia. Recent surveillance studies showed that CTX-M-27 is emerging in certain parts of the world especially in Japan and Europe. The population structure of ESBL-producing E. coli is dominated globally by an high-risk clone named ST131. Escherichia coli ST131 belongs to three clades (A, B, and C) and three different subclades (C1, C1-M27, and C2). Clade C1-M27 is associated with blaCTX-M-27, and C2 with blaCTX-M-15. Recent whole genome sequencing studies have shown that clade C has evolved from clade B in a stepwise fashion, resulting in one of the most influential global antimicrobial resistance clones that has emerged during the 2000's. Other important E. coli clones that have been detected among ESBL producers include ST405, ST38, ST648, ST410, and ST1193. The INCREMENT project has shown that ertapenem is as effective as other carbapenems for treating serious infections due to ESBL-producing Enterobacteriaceae. The results of the MERINO open-label randomized controlled study has provided clear evidence that piperacillin-tazobactam should be avoided for targeted therapy of blood-stream infections due to ESBL-producing E. coli and K. pneumoniae, regardless of the patient population, source of infection, bacterial species, and susceptibility result of piperacillin-tazobactam. Research is still warranted to define the optimal therapy of less severe infections due to ESBL-producing Enterobactericeae.


Assuntos
Antibacterianos/farmacologia , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Enterobacteriaceae/microbiologia , Enterobacteriaceae/efeitos dos fármacos , beta-Lactamases/metabolismo , Animais , Enterobacteriaceae/metabolismo , Humanos , Epidemiologia Molecular/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto
7.
Artigo em Inglês | MEDLINE | ID: mdl-31426735

RESUMO

The Australian Group on Antimicrobial Resistance (AGAR) performs regular period-prevalence studies to monitor changes in antimicrobial resistance in selected enteric Gram-negative pathogens. The 2017 survey was the fifth year to focus on blood stream infections, and included Enterobacterales, Pseudomonas aeruginosa and Acinetobacter species. Seven thousand nine hundred and ten isolates, comprising Enterobacterales (7,100, 89.8%), P. aeruginosa (697, 8.8%) and Acinetobacter species (113, 1.4%), were tested using commercial automated methods. The results were analysed using Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints (January 2018). Of the key resistances, non-susceptibility to the third-generation cephalosporin, ceftriaxone, was found in 11.3%/11.3% of Escherichia coli (CLSI/EUCAST criteria), 8.8%/8.8% of Klebsiella pneumoniae, and 5.7%/5.7% of K. oxytoca. Non-susceptibility rates to ciprofloxacin were 12.1%/18.0% for E. coli, 4.4%/11.2% for K. pneumoniae, 1.3%/3.5% for K. oxytoca, 3.0%/8.5% for Enterobacter cloacae complex, and 5.1%/9.8% for P. aeruginosa. Resistance rates to piperacillin-tazobactam were 2.8%/5.9%, 3.7%/7.3%, 9.6%/11.0%, 22.5%/27.6%, and 6.4%/13.2% for the same five species respectively. Twenty-seven isolates from 25 patients were shown to harbour a carbapenemase gene: 12 blaIMP (11 patients), five blaOXA-181 (four patients), three blaOXA-23, two blaNDM, two blaKPC, two blaVIM, and one blaGES.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Sepse/tratamento farmacológico , Sepse/epidemiologia , Sepse/microbiologia , Relatórios Anuais como Assunto , Austrália/epidemiologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Infecção Hospitalar/tratamento farmacológico , Infecções por Enterobacteriaceae/tratamento farmacológico , Escherichia coli/efeitos dos fármacos , Humanos , Klebsiella pneumoniae/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Tipagem Molecular , Avaliação de Resultados da Assistência ao Paciente , Pseudomonas aeruginosa/efeitos dos fármacos , beta-Lactamases/genética , beta-Lactamases/metabolismo
8.
Biomed Res Int ; 2019: 6736897, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31467906

RESUMO

The aim of this study was to investigate the mechanisms responsible for resistance to antimicrobials in a collection of enterobacterial isolates recovered from two hospitals in Saudi Arabia. A total of six strains isolated from different patients showing high resistance to carbapenems was recovered in 2015 from two different hospitals, with four being Klebsiella pneumoniae and two Enterobacter cloacae. All isolates except one K. pneumoniae were resistant to tigecycline, but only one K. pneumoniae was resistant to colistin. All produced a carbapenemase according to the Carba NP test, and all were positive for the EDTA-disk synergy test for detection of MBL. Using PCR followed by sequencing, the four K. pneumoniae isolates produced the carbapenemase NDM-1, while the two E. cloacae isolates produced the carbapenemase VIM-1. Genotyping analysis by Multilocus Sequence Typing (MLST) showed that three out of the four K. pneumoniae isolates were clonally related. They had been recovered from the same hospital and belonged to Sequence Type (ST) ST152. In contrast, the fourth K. pneumoniae isolate belonged to ST572. Noticeably, the NDM-1-producing K. pneumoniae additionally produced an extended-spectrum ß-lactamase (ESBL) of the CTX-M type, together with OXA-1 and TEM-1. Surprisingly, the three clonally related isolates produced different CTX-M variants, namely, CTX-M-3, CTX-M-57, and CTX-M-82, and coproduced QnrB, which confers quinolone resistance, and the 16S rRNA methylase RmtC, which confers high resistance to all aminoglycosides. The AAC(6')-Ib acetyltransferase was detected in both K. pneumoniae and E. cloacae. Mating-out assays using Escherichia coli as recipient were successful for all isolates. The bla NDM-1 gene was always identified on a 70-kb plasmid, whereas the bla VIM-1 gene was located on either a 60-kb or a 150-kb plasmid the two E. cloacae isolates, respectively. To the best of our knowledge, this is the first report of the coexistence of an MBL (NDM-1), an ESBL (CTX-M), a 16S rRNA methylase (RmtC), an acetyltransferase (AAC[6']-Ib), and a quinolone resistance enzyme (QnrB) in K. pneumoniae isolates recovered from different patients during an outbreak in a Saudi Arabian hospital.


Assuntos
Proteínas de Bactérias/genética , Farmacorresistência Bacteriana/genética , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Klebsiella/tratamento farmacológico , beta-Lactamases/genética , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/farmacologia , Carbapenêmicos/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Enterobacter cloacae/efeitos dos fármacos , Enterobacter cloacae/genética , Enterobacter cloacae/patogenicidade , Infecções por Enterobacteriaceae/genética , Infecções por Enterobacteriaceae/microbiologia , Feminino , Humanos , Infecções por Klebsiella/genética , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/patogenicidade , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , RNA Ribossômico 16S/genética , Arábia Saudita/epidemiologia
9.
Farm Hosp ; 43(5): 151-157, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31469627

RESUMO

OBJECTIVE: To determine the percentage of patients given standard doses of piperacillin/tazobactam or meropenem by continuous  infusion who achieved the target pharmacokinetic/pharmacodynamic  (PK/PD) index, which was defined as free concentrations four times  more than the minimum inhibitory concentration (CMI) for 100% of the  dosing interval (100% fT≥ 4 x MIC). METHOD: Preliminary data from a larger prospective clinical study  analysing the PK/PD behaviour of ß-lactams antibiotics continuous  infusion (CI) in critical patients. The study was conducted in the  intensive care units of a tertiary university hospital for adults (June  2015-May 2017). Inclusion criteria: normal renal function (glomerular  renal function (GFR) CKD-EPI formula ≥ 60 mL/min/1.73 m2) and  treatment with standard dose ß-lactams CI. Concentrations at steady  state (Css) conditions were determined using UHPLC-MS/MS. We  selected the highest susceptible MIC for all likely organisms according to  European Commitee on Antimicrobial Susceptibility Testing's (i.e.  piperacillin/tazobactam: 8 mg/L for enterobacteriaceae and 16 mg/L for  Pseudomonas aeruginosa; meropenem: 2 mg/L for any  microorganism). In addition, a subanalysis of patients was conducted using actual MIC values. RESULTS: 61 patients were enrolled (25 to meropenem and 36 to  piperacillin/tazobactam). Average age was 59 (15) years and median  GFR rate was 95 mL/min/1.73 m2 (83-115). Median meropenem and  piperacillin free concentrations were 16 mg/L (11-29) and 40 mg/L (21- 51), respectively. 88% of patients treated with meropenem reached the  PK/PD target, without differences between both microorganisms. For  piperacillin/tazobactam, 61% and 11% of patients reached the target,  with enterobacteriaceae and Pseudomonas as suspected  microorganisms, respectively. The pathogen was isolated in 35 (57%)  patients: 94% reached the target PK/PD, without differences between  both antibiotic therapies. CONCLUSIONS: Standard doses of meropenem CI are sufficient to  achieve a PK/PD target of 100% fT≥ 4 x MIC in suspected infections  with high MICs (Pseudomonas aeruginosa or enterobacteriaceae).  However, higher doses of piperacillin/tazobactam could be considered to  achieve this goal. In patients with isolated microorganisms, a  standard dose of both antibiotic therapies would be sufficient to achieve  the target. Therapeutic drug monitoring is highly recommended for  therapeutic optimization.


Assuntos
Antibacterianos/administração & dosagem , Estado Terminal/terapia , Meropeném/administração & dosagem , Combinação Piperacilina e Tazobactam/administração & dosagem , Adulto , Idoso , Antibacterianos/sangue , Antibacterianos/farmacocinética , Antibacterianos/uso terapêutico , Estudos Clínicos como Assunto/estatística & dados numéricos , Infecção Hospitalar/tratamento farmacológico , Infecções por Enterobacteriaceae/tratamento farmacológico , Feminino , Hospitais Universitários , Humanos , Infusões Intravenosas , Unidades de Terapia Intensiva , Masculino , Meropeném/sangue , Meropeném/farmacocinética , Meropeném/uso terapêutico , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Combinação Piperacilina e Tazobactam/sangue , Combinação Piperacilina e Tazobactam/farmacocinética , Combinação Piperacilina e Tazobactam/uso terapêutico , Estudos Prospectivos , Infecções por Pseudomonas/tratamento farmacológico , Centros de Atenção Terciária
10.
Bull World Health Organ ; 97(7): 486-501B, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31258218

RESUMO

Objective: To make a systematic review of risk factors, outcomes and prevalence of extended-spectrum ß-lactamase-associated infection in children and young adults in South-East Asia and the Western Pacific. Methods: Up to June 2018 we searched online databases for published studies of infection with extended-spectrum ß-lactamase-producing Enterobacteriaceae in individuals aged 0-21 years. We included case-control, cohort, cross-sectional and observational studies reporting patients positive and negative for these organisms. For the meta-analysis we used random-effects modelling of risk factors and outcomes for infection, and meta-regression for analysis of subgroups. We mapped the prevalence of these infections in 20 countries and areas using available surveillance data. Findings: Of 6665 articles scanned, we included 40 studies from 11 countries and areas in the meta-analysis. The pooled studies included 2411 samples testing positive and 2874 negative. A higher risk of infection with extended-spectrum ß-lactamase-producing bacteria was associated with previous hospital care, notably intensive care unit stays (pooled odds ratio, OR: 6.5; 95% confidence interval, CI: 3.04 to 13.73); antibiotic exposure (OR: 4.8; 95% CI: 2.25 to 10.27); and certain co-existing conditions. Empirical antibiotic therapy was protective against infection (OR: 0.29; 95% CI: 0.11 to 0.79). Infected patients had longer hospital stays (26 days; 95% CI: 12.81 to 38.89) and higher risk of death (OR: 3.2; 95% CI: 1.82 to 5.80). The population prevalence of infection was high in these regions and surveillance data for children were scarce. Conclusion: Antibiotic stewardship policies to prevent infection and encourage appropriate treatment are needed in South-East Asia and the Western Pacific.


Assuntos
Resistência Microbiana a Medicamentos , Infecções por Enterobacteriaceae/tratamento farmacológico , Enterobacteriaceae/efeitos dos fármacos , beta-Lactamases/metabolismo , Ásia Sudeste/epidemiologia , Criança , Enterobacteriaceae/enzimologia , Infecções por Enterobacteriaceae/microbiologia , Humanos , Ilhas do Pacífico/epidemiologia , Fatores de Risco
11.
BMJ Case Rep ; 12(7)2019 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-31300600

RESUMO

A late preterm male infant of 36 weeks gestation and a birth weight of 2100 g was admitted on day 35 of life with complaints of respiratory distress and lethargy. He was diagnosed as a case of sepsis screen positive culture negative sepsis and was managed with respiratory support and intravenous antibiotics for 10 days. The infant improved clinically and was on spoon feeds by day 14 of admission. On day 14 of admission, he developed new-onset respiratory distress and was diagnosed as a case of nosocomial pneumonia based on chest radiography findings. The blood culture grew a rare organism Cedecea lapagei and a diagnosis of sepsis was also made. The antibiotics were tailored as per the blood culture sensitivity pattern and the infant had clinical improvement in the next 72 hours.


Assuntos
Antibacterianos/uso terapêutico , Infecções por Enterobacteriaceae/diagnóstico , Enterobacteriaceae/isolamento & purificação , Combinação Piperacilina e Tazobactam/uso terapêutico , Respiração Artificial , Síndrome do Desconforto Respiratório do Recém-Nascido/microbiologia , Sepse/diagnóstico , Enterobacteriaceae/classificação , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Enterobacteriaceae/fisiopatologia , Humanos , Lactente , Letargia , Masculino , Respiração Artificial/efeitos adversos , Síndrome do Desconforto Respiratório do Recém-Nascido/tratamento farmacológico , Síndrome do Desconforto Respiratório do Recém-Nascido/fisiopatologia , Sepse/tratamento farmacológico , Punção Espinal , Resultado do Tratamento
12.
Indian J Med Res ; 149(2): 185-191, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-31219082

RESUMO

Background & objectives: The escalation in carbapenem resistance among Enterobacteriaceae has resulted in a lack of effective therapeutic alternatives. Older antimicrobials, fosfomycin, nitrofurantoin and colistin for urinary tract infections (UTIs) caused by carbapenem-resistant Enterobacteriaceae (CRE) may be effective treatment options. The objectives of this study were to evaluate the utility of fosfomycin, nitrofurantoin and colistin in treating UTI caused by CRE and molecular characterization of the plasmid-mediated carbapenem resistance mechanisms. Methods: Consecutive, non-duplicate isolates of CR Escherichia coli and Klebsiella spp. from urine cultures were included (n=150). Minimum inhibitory concentrations (MIC) were determined by E-test (fosfomycin and nitrofurantoin) and broth microdilution (colistin). Efficacy ratios were derived by dividing susceptibility breakpoints by observed MIC values of the drugs for the isolates. Isolates were screened for genes coding for carbapenemases using multiplex PCR. Fosfomycin, nitrofurantoin and colistin-resistant isolates were screened for plasmid-borne resistance genes fos A3, oqx AB and mcr-1, respectively using PCR. Results: Among E. coli, 98.9, 56 and 95 per cent isolates were susceptible to fosfomycin, nitrofurantoin and colistin, respectively, while 94 and 85 per cent of Klebsiella spp. were susceptible to fosfomycin and colistin, respectively. The efficacy ratios indicated fosfomycin as the drug of choice for UTI caused by CR E. coli and Klebsiella spp., followed by colistin. The blaNDM gene was most common, followed by blaOXA48-like. Plasmid-borne genes encoding resistance to fosfomycin, nitrofurantoin and colistin were absent. Interpretation & conclusions: With increasing resistance against the current treatment options, older drugs may emerge as effective options. Molecular screening of resistant isolates is essential to prevent the spread of plasmid-borne resistance against these drugs.


Assuntos
Proteínas de Bactérias/genética , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções Urinárias/tratamento farmacológico , beta-Lactamases/genética , Proteínas de Bactérias/efeitos dos fármacos , Enterobacteriáceas Resistentes a Carbapenêmicos/enzimologia , Enterobacteriáceas Resistentes a Carbapenêmicos/patogenicidade , Colistina/uso terapêutico , Infecções por Enterobacteriaceae/genética , Infecções por Enterobacteriaceae/microbiologia , Fosfomicina/uso terapêutico , Humanos , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/patogenicidade , Testes de Sensibilidade Microbiana , Nitrofurantoína/uso terapêutico , Infecções Urinárias/genética , Infecções Urinárias/microbiologia , beta-Lactamases/efeitos dos fármacos
13.
Indian J Med Res ; 149(2): 216-221, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-31219086

RESUMO

Background & objectives: Nosocomial infections caused by multidrug-resistant, Pseudomonas species have become a major clinical and public health concern. The aim of this study was to characterize phenotypic and genotypic profile of antimicrobial resistance (AMR) in Pseudomonas spp. isolated from hospitalized patients. Methods: A total of 126 consecutive, non-duplicate isolates of Pseudomonas spp. isolated from various clinical samples were included in the study over a period of two years. Identification and antimicrobial sensitivity was performed using automated culture system according to the Clinical and Laboratory Standards Institute (CLSI) recommendations. Phenotypic detection of extended-spectrum ß-lactamases (ESBLs), Amp-C ß-lactamase (AmpC) and metallo-ß-lactamases (MBLs) were done by various combinations of disc-diffusion and E-test methods, followed by polymerase chain reaction-based detection of ß-lactamase-encoding genes. Results: Among 126 clinical isolates, 121 (96.1%) isolates were identified as Pseudomonas aeruginosa. Most of the isolates were recovered from pus sample, 35 (27.8%) followed by urine, 25 (19.84%); endotracheal aspirate, 24 (19.04%); blood, 14 (11.11%) and sputum, four (3.17%). The highest rate of resistance was against ticarcillin-clavulanic acid, 113 (89.7%) followed by meropenem, 92 (72.5%) and ceftazidime, 91 (72.3%). Overall, ESBLs, AmpC and carbapenemase production was detected in 109 (96.4%), 64 (50.8%) and 105 (94.6%) isolates by phenotypic methods. The most prevalent ESBL gene was blaTEMin 72 (57.1%) and the least prevalent was blaSHVin 19 (15.1%) isolates. AmpC gene was seen less compared to ESBL gene. The most prevalent carbapenemases gene was blaNDM-141 (46.06%) followed by blaVIM and blaOXA-1. Interpretation & conclusions: Our findings suggested that a high rate of ESBLs and carbapenemases production was observed in Pseudomonas spp. Therefore, phenotypic and genotypic detection of AMR needs to be combined for better characterization of resistance patterns in Pseudomonas spp.


Assuntos
Farmacorresistência Bacteriana/genética , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/genética , Adulto , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Proteínas de Bactérias/genética , Infecções por Enterobacteriaceae/epidemiologia , Infecções por Enterobacteriaceae/genética , Infecções por Enterobacteriaceae/microbiologia , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Infecções por Pseudomonas/epidemiologia , Infecções por Pseudomonas/genética , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/patogenicidade , beta-Lactamases/genética
14.
Nat Microbiol ; 4(10): 1627-1635, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31209306

RESUMO

Antibiotic-resistant bacteria are a significant threat to human health, with one estimate suggesting they will cause 10 million worldwide deaths per year by 2050, surpassing deaths due to cancer1. Because new antibiotic development can take a decade or longer, it is imperative to effectively use currently available drugs. Antibiotic combination therapy offers promise for treating highly resistant bacterial infections, but the factors governing the sporadic efficacy of such regimens have remained unclear. Dogma suggests that antibiotics ineffective as monotherapy can be effective in combination2. Here, using carbapenem-resistant Enterobacteriaceae (CRE) clinical isolates, we reveal the underlying basis for the majority of effective combinations to be heteroresistance. Heteroresistance is a poorly understood mechanism of resistance reported for different classes of antibiotics3-6 in which only a subset of cells are phenotypically resistant7. Within an isolate, the subpopulations resistant to different antibiotics were distinct, and over 88% of CRE isolates exhibited heteroresistance to multiple antibiotics ('multiple heteroresistance'). Combinations targeting multiple heteroresistance were efficacious, whereas those targeting homogenous resistance were ineffective. Two pan-resistant Klebsiella isolates were eradicated by combinations targeting multiple heteroresistance, highlighting a rational strategy to identify effective combinations that employs existing antibiotics and could be clinically implemented immediately.


Assuntos
Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Infecções por Enterobacteriaceae/tratamento farmacológico , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Enterobacteriáceas Resistentes a Carbapenêmicos/crescimento & desenvolvimento , Enterobacteriáceas Resistentes a Carbapenêmicos/isolamento & purificação , Ceftazidima/farmacologia , Colistina/farmacologia , Quimioterapia Combinada , Infecções por Enterobacteriaceae/microbiologia , Fosfomicina/farmacologia , Klebsiella/efeitos dos fármacos , Klebsiella/crescimento & desenvolvimento , Klebsiella/isolamento & purificação , Testes de Sensibilidade Microbiana
15.
PLoS Med ; 16(6): e1002825, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31173597

RESUMO

BACKGROUND: Primary care antimicrobial stewardship interventions can improve antimicrobial prescribing, but there is less evidence that they reduce rates of resistant infection. This study examined changes in broad-spectrum antimicrobial prescribing in the community and resistance in people admitted to hospital with community-associated coliform bacteraemia associated with a primary care stewardship intervention. METHODS AND FINDINGS: Segmented regression analysis of data on all patients registered with a general practitioner in the National Health Service (NHS) Tayside region in the east of Scotland, UK, from 1 January 2005 to 31 December 2015 was performed, examining associations between a primary care antimicrobial stewardship intervention in 2009 and primary care prescribing of fluoroquinolones, cephalosporins, and co-amoxiclav and resistance to the same three antimicrobials/classes among community-associated coliform bacteraemia. Prescribing outcomes were the rate per 1,000 population prescribed each antimicrobial/class per quarter. Resistance outcomes were proportion of community-associated (first 2 days of hospital admission) coliform (Escherichia coli, Proteus spp., or Klebsiella spp.) bacteraemia among adult (18+ years) patients resistant to each antimicrobial/class. 11.4% of 3,442,205 oral antimicrobial prescriptions dispensed in primary care over the study period were for targeted antimicrobials. There were large, statistically significant reductions in prescribing at 1 year postintervention that were larger by 3 years postintervention when the relative reduction was -68.8% (95% CI -76.3 to -62.1) and the absolute reduction -6.3 (-7.6 to -5.2) people exposed per 1,000 population per quarter for fluoroquinolones; relative -74.0% (-80.3 to -67.9) and absolute reduction -6.1 (-7.2 to -5.2) for cephalosporins; and relative -62.3% (-66.9 to -58.1) and absolute reduction -6.8 (-7.7 to -6.0) for co-amoxiclav, all compared to their prior trends. There were 2,143 eligible bacteraemia episodes involving 2,004 patients over the study period (mean age 73.7 [SD 14.8] years; 51.4% women). There was no increase in community-associated coliform bacteraemia admissions associated with reduced community broad-spectrum antimicrobial use. Resistance to targeted antimicrobials reduced by 3.5 years postintervention compared to prior trends, but this was not statistically significant for co-amoxiclav. Relative and absolute changes were -34.7% (95% CI -52.3 to -10.6) and -63.5 (-131.8 to -12.8) resistant bacteraemia per 1,000 bacteraemia per quarter for fluoroquinolones; -48.3% (-62.7 to -32.3) and -153.1 (-255.7 to -77.0) for cephalosporins; and -17.8% (-47.1 to 20.8) and -63.6 (-206.4 to 42.4) for co-amoxiclav, respectively. Overall, there was reversal of a previously rising rate of fluoroquinolone resistance and flattening of previously rising rates of cephalosporin and co-amoxiclav resistance. The limitations of this study include that associations are not definitive evidence of causation and that potential effects of underlying secular trends in the postintervention period and/or of other interventions occurring simultaneously cannot be definitively excluded. CONCLUSIONS: In this population-based study in Scotland, compared to prior trends, there were very large reductions in community broad-spectrum antimicrobial use associated with the stewardship intervention. In contrast, changes in resistance among coliform bacteraemia were more modest. Prevention of resistance through judicious use of new antimicrobials may be more effective than trying to reverse resistance that has become established.


Assuntos
Antibacterianos/uso terapêutico , Gestão de Antimicrobianos/normas , Farmacorresistência Bacteriana/efeitos dos fármacos , Enterobacteriaceae/efeitos dos fármacos , Análise de Séries Temporais Interrompida/normas , Médicos de Atenção Primária/normas , Antibacterianos/farmacologia , Gestão de Antimicrobianos/métodos , Prescrições de Medicamentos/normas , Farmacorresistência Bacteriana/fisiologia , Enterobacteriaceae/fisiologia , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Enterobacteriaceae/epidemiologia , Humanos , Análise de Séries Temporais Interrompida/métodos , Médicos de Atenção Primária/educação , Vigilância da População , Atenção Primária à Saúde/métodos , Atenção Primária à Saúde/normas , Escócia/epidemiologia
16.
J Infect Chemother ; 25(11): 894-900, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31178280

RESUMO

The gut microbiota may play a pivotal role in controlling the antimicrobial resistant (AMR) organisms although the evidences are limited. We investigated the effects of gut microbiota on the growth of AMR organisms, ß-lactamases activity and transmissibility of antimicrobial resistant properties of the extended spectrum ß-lactamase (ESBL)-producing Escherichia coli and carbapenem-resistant Enterobacteriaceae. CTX-M-15-positive, ESBL-producing E. coli and carbapenem resistant Enterobacteriaceae, Bacteroides fragilis, Bifidobacterium longum, Clostridium butyricum, Clostridioides difficile, Clostridium perfringens, Enterococcus faecium, Lactobacillus plantarum and probiotic strain of C. butyricum MIYAIRI 588 were used in this study. The growth of AMR organisms was suppressed by the supernatant of C. butyricum, C. difficile, C. perfringens, E. faecium and L. plantarum in a dose dependent manner but not by that of B. fragilis and B. longum. The ß-lactamase activity produced by E. coli was reduced by the presence of culture supernatant of certain gut microbiota during stationary phase of E. coli. Importantly, C. butyricum MIYAIRI 588 culture supernatant suppressed the transcription of blaCTX-M gene during growth phase of E. coli. The conjugation assay showed the reduction of transmissibility of antibiotic resistant gene by gut microbiota. These findings suggest that certain gut microbiota affect the antibiotic resistant activities of AMR organisms. Further studies are needed to identify the specific mechanism(s) of these actions between AMR organisms and gut microbiota.


Assuntos
Antibacterianos/uso terapêutico , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Carbapenêmicos/uso terapêutico , Infecções por Enterobacteriaceae/tratamento farmacológico , Microbioma Gastrointestinal/fisiologia , Probióticos/uso terapêutico , beta-Lactamases/metabolismo , Infecções por Enterobacteriaceae/microbiologia , Humanos , Testes de Sensibilidade Microbiana/métodos
17.
Int J Antimicrob Agents ; 54(2): 189-196, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31075401

RESUMO

Carbapenems are considered the treatment of choice for extended-spectrum ß-lactamase (ESBL)- or AmpC ß-lactamase-producing Enterobacteriaceae bacteraemia. Data on the effectiveness of non-intravenous carbapenem-sparing antibiotic options are limited. This study compared the 30-day mortality and clinical failure associated with the use of carbapenems versus alternative non-intravenous antibiotics for the definitive treatment of ESBL/AmpC-positive Enterobacteriaceae bacteraemia. This 12-year retrospective study (2004-2015) included all patients with bacteraemia due to ESBL/AmpC-producing Enterobacteriaceae at a Spanish hospital. Given the lack of randomisation of initial therapies, a propensity score for receiving carbapenems was calculated. There were 1115 patients with a first episode of bacteraemia due to Escherichia coli or Klebsiella pneumoniae, of which 123 (11.0%) were ESBL/AmpC-positive. There were 101 eligible patients: 59 in the carbapenem group and 42 in the alternative treatment group (trimethoprim/sulfamethoxazole 59.5%, quinolones 21.4%). The most frequent sources of infection were urinary (63%) and biliary (15%). Compared with the carbapenem group, patients treated with an alternative regimen had a shorter hospital stay [median (IQR) 7 (5-10) days vs. 12 (9-18) days; P < 0.001]. Use of an alternative non-intravenous therapy did not increase mortality (OR = 0.27, 95% CI 0.05-1.61; P = 0.15). After controlling for confounding factors with the propensity score, the adjusted OR of carbapenem treatment was 4.95 (95% CI 0.94-26.01; P = 0.059). Alternative non-intravenous carbapenem-sparing antibiotics could have a role in the definitive treatment of ESBL/AmpC-positive Enterobacteriaceae bacteraemia, allowing a reduction in carbapenem use. Use of trimethoprim/sulfamethoxazole in this series showed favourable results.


Assuntos
Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Infecções por Enterobacteriaceae/tratamento farmacológico , Enterobacteriaceae/enzimologia , beta-Lactamases/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bacteriemia/mortalidade , Infecções por Enterobacteriaceae/mortalidade , Feminino , Hospitais , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Estudos Retrospectivos , Espanha , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
18.
Microb Drug Resist ; 25(8): 1182-1190, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31140920

RESUMO

Extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-PE) are important causes of serious infections in intensive care unit (ICU). This study aimed to investigate the risk factors for intestinal carriage of ESBL-PE among patients admitted to ICU, subsequent ESBL-PE infections, and outcomes of these patients. This study prospectively collected rectal swabs from 215 ICU patients in Northern Thailand and ESBL-PE were isolated. A high prevalence of ESBL-PE carriage (134/215, 62.3%) at ICU admission was observed, with Escherichia coli representing the predominant organism (67.5%) followed by Klebsiella pneumoniae (19.4%). Multivariate logistic regression analysis identified chronic renal disease as the independent risk factor for ESBL-PE carriage (p = 0.009; adjusted odds ratio = 4.369; 95% confidence interval = 1.455-13.119). Among colonized patients, 2.2% (3/134) developed ESBL-PE infections during ICU stay. Phylogenetic analysis of E. coli (n = 108) showed that the predominant group was group A (38.0%), followed by groups B1 (17.6%), D (15.7%), B2 (14.8%), C (7.4%), and F (6.5%). Multilocus sequence typing analysis of the pathogenic groups B2, D, and F revealed 11 different sequence types (STs), with ST131 (n = 13) as the most prevalent, followed by ST648 (n = 5), ST38 (n = 4), ST393 (n = 3), and ST1193 (n = 3). These results are of concern since ESBL-PE may be a prerequisite for endogenous infections and potentially disseminate within the hospital. This is the first study describing ESBL-PE carriage among patients at ICU admission and subsequent ESBL-PE infections in Thailand.


Assuntos
Infecções por Enterobacteriaceae/microbiologia , Enterobacteriaceae/isolamento & purificação , beta-Lactamases/metabolismo , Antibacterianos/uso terapêutico , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/metabolismo , Infecções por Enterobacteriaceae/tratamento farmacológico , Fezes/microbiologia , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Testes de Sensibilidade Microbiana/métodos , Pessoa de Meia-Idade , Filogenia , Estudos Prospectivos , Fatores de Risco , Centros de Atenção Terciária , Tailândia
19.
BMJ Case Rep ; 12(5)2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31142484

RESUMO

Diagnosis of postenteritic reactive arthritis (ReA) is a challenge and might have a broad range of differential diagnoses. A 50-year-old man was referred to our attention because of persistent inflammatory low back pain and asymmetric oligoarthritis. The clinical history was positive for diarrhoea in the previous 3 months. Inflammatory bowel disease, Whipple and celiac diseases were carefully excluded. In addition, serology, stool cultures, biopsies from the upper gastrointestinal tract yielded negative results for infections. A presumptive diagnosis of ReA was done and a non-steroidal anti-inflammatory drug trial prescribed. Persistence of symptoms prompted us for a second look of the colon. Biopsy collected from the terminal ileum were cultured and surprisingly colonies of Hafnia alvei, a rod-shaped Enterobacteriaceae, were detected. Treatment with ciprofloxacin leads to fast symptoms resolution. Although enterocolitis from H. alvei has been rarely reported, the culture of intestinal specimens might be recommended in the work-up of patients with suspected postenteritic ReA.


Assuntos
Artrite Reativa/microbiologia , Infecções por Enterobacteriaceae/diagnóstico por imagem , Hafnia alvei , Antibacterianos/administração & dosagem , Artrite Reativa/diagnóstico por imagem , Ciprofloxacino/administração & dosagem , Diagnóstico Diferencial , Esquema de Medicação , Quimioterapia Combinada , Infecções por Enterobacteriaceae/tratamento farmacológico , Enterocolite/tratamento farmacológico , Enterocolite/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Probióticos/administração & dosagem , Cintilografia/métodos , Resultado do Tratamento
20.
Rev Chilena Infectol ; 36(1): 9-15, 2019 Feb.
Artigo em Espanhol | MEDLINE | ID: mdl-31095199

RESUMO

BACKGROUND: Ertapenem has proven to be effective for extended-spectrum beta-lactamases-producing Enterobacteriaceae but lacks activity against non-fermenters; de-escalation to this antibiotic may reduce the selection of resistance to Pseudomonas aeruginosa and improve clinical outcomes. AIM: To evaluate the clinical impact of de-escalation from broad-spectrum anti-pseudomonal agents to ertapenem, a non-pseudomonal antibiotics for Enterobacteriaceae infections in critically-ill patients. METHODS: We conducted a prospective cohort study in adult patients admitted to intensive care units (ICUs) who had Enterobacteriaceae infections and were de-escalated from empiric anti-pseudomonal coverage to non-pseudomonal antibiotics. Cox proportional hazards models were performed comparing all-cause mortality and length of hospital stay between patients who remained on anti-pseudomonal coverage versus those who were de-escalated to ertapenem. RESULTS: 105 patients in the anti-pseudomonal group were compared to 148 patients in the ertapenem de-escalation group. De-escalation was associated with lower all-cause mortality compared to patients who remained on anti-pseudomonal coverage (adjusted Hazard Ratio 0.24; 95% CI: 0.12-0.46). The length of ICU stay was similar between the groups. DISCUSSION: ICU patients with Enterobacteriaceae infections de-escalated to ertapenem therapy had better outcomes compared to patients who remained on broad-spectrum, anti-pseudomonal therapy, suggesting that de-escalation is a safe approach amongst ICU patients.


Assuntos
Antibacterianos/administração & dosagem , Infecções por Enterobacteriaceae/tratamento farmacológico , Ertapenem/administração & dosagem , Unidades de Terapia Intensiva , Adulto , Idoso , Colômbia , Estado Terminal , Infecções por Enterobacteriaceae/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Pseudomonas/efeitos dos fármacos , Fatores de Risco , Estatísticas não Paramétricas , Fatores de Tempo , Resultado do Tratamento
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