Introduction 
Despite evidence of the high prevalence of antibiotic resistant infections in developing countries, studies on the clinical and economic impact of antibiotic resistance (ABR) to inform interventions to contain its emergence and spread are limited. The aim of this study was to analyze the published literature on the clinical and economic implications of ABR in developing countries.


Methods 
A systematic search was carried out in Medline via PubMed and Web of Sciences and included studies published from January 01, 2000 to December 09, 2016. All papers were considered and a quality assessment was performed using the Newcastle-Ottawa quality assessment scale (NOS).


Results 
Of 27 033 papers identified, 40 studies met the strict inclusion and exclusion criteria and were finally included in the qualitative and quantitative analysis. Mortality was associated with resistant bacteria, and statistical significance was evident with an odds ratio (OR) 2.828 (95%CI, 2.231–3.584; p = 0.000). ESKAPE pathogens was associated with the highest risk of mortality and with high statistical significance (OR 3.217; 95%CIs; 2.395–4.321; p = 0.001). Eight studies showed that ABR, and especially antibiotic-resistant ESKAPE bacteria significantly increased health care costs.


Conclusion 
ABR is associated with a high mortality risk and increased economic costs with ESKAPE pathogens implicated as the main cause of increased mortality. Patients with non-communicable disease co-morbidities were identified as high-risk populations.

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Clinical and economic impact of antibiotic resistance in developing countries: A systematic review and meta-analysis.

Background and objectives: Bacteraemia caused by Enterobacteriaceae (EB) producing extended-spectrum b-lactamase (ESBL+) has been associated with higher mortality compared with non-ESBL-producing (ESBL2) EB bacteraemia in observational studies. We conducted a systematic review and meta-analysis of these studies to assess how adjusting for confounding in multivariate analyses affects the pooled estimate, and whether multivariate analyses that include intermediates in the causal pathway of outcome (sepsis severity and inadequate empirical therapy) have lower estimates of attributable mortality. Data sources: PubMed search on 23 November 2010 followed by manually searching reference lists of included studies. Study eligibility criteria: Cohort studies published in English with separate mortality rates for ESBL+ and ESBL2 EB bacteraemia. Synthesis methods: Random-effects pooling of unadjusted and adjusted ORs followed by subgroup analyses to explore effects of adjustment procedures on adjusted ORs. Results: The pooled OR for the unadjusted mortality associated with ESBL production was 2.35 (95% CI 1.90– 2.91, I 2 ¼ 42%, 32 studies). The pooled adjusted OR was 1.52 (95% CI 1.15– 2.01, I 2 ¼ 32%, 15 studies). Adjustment for more intermediates was associated with decreasing ORs. The pooled OR for the analyses adjusting for inadequate empirical therapy was 1.37 (95% CI 1.04 –1.82). Conclusions: ESBL production in EB bacteraemia is associated with a higher mortality compared with bacteraemia with ESBL2 EB, although the estimate of this association is affected by adjustment procedures. Adjustment for inadequate empirical therapy leads to a reduction in ORs, indicating that higher mortality is likely to be mediated through this phenomenon.

/pdf/effects-of-confounders-and-intermediates-on-the-association-4g29zrqtvp.pdf

Effects of confounders and intermediates on the association of bacteraemia caused by extended-spectrum β-lactamase-producing Enterobacteriaceae and patient outcome: a meta-analysis

A high proportion of Extended-Spectrum-Beta-Lactamase (ESBL) producing Enterobacteriaceae is causing common infections in all regions of the world. The burden of antibiotic resistance due to ESBL in East Africa is large but information is scarce and thus it is unclear how big the problem really is. To gain insight into the magnitude and molecular epidemiology of ESBL-producing Enterobacteriaceae in East Africa a literature search was performed in PubMed on 31 July 2015 to retrieve articles with relevant information on ESBL. Meta-analysis was performed to determine overall proportion estimate of ESBL-producing Enterobacteriaceae. A total of 4076 bacterial isolates were included in the analysis. The overall pooled proportion of ESBL-producing Enterobacteriaceae among included surveys done in East African hospitals was found to be 0.42 (95 % CI: 0.34–0.50). Heterogeneity (I2) between countries’ proportions in ESBL was significantly high (96.95 % and p < 0.001). The frequently detected genes encoding ESBL were CTX-M, TEM, SHV and OXA while the most infrequent reported genes were KPC and NDM. The available studies show a very wide variation in resistance due to ESBL between countries. This highlights a need for active surveillance systems which can help understand the actual epidemiology of ESBL, aid in formulating national or regional guidelines for proper screening of ESBL, and support developing standardized approaches for managing patients colonized with ESBL.

/pdf/meta-analysis-of-proportion-estimates-of-extended-spectrum-57a1s967nl.pdf

Meta-analysis of Proportion Estimates of Extended-Spectrum-Beta-Lactamase-producing Enterobacteriaceae in East Africa hospitals.

Extended-spectrum β-lactamases (ESBLs) have been increasingly described worldwide, especially among Enterobacteriaceae isolates, and recently not only in the nosocomial, but also in the community setting. Bloodstream infections (BSIs) caused by ESBL-producing Enterobacteriaceae have been associated with increased rates of treatment failure, mortality and hospital costs. Any delay in the initiation of adequate antibiotic therapy is potentially lethal for patients with BSIs caused by ESBL-producing Enterobacteriaceae. The awareness of changes in bacterial resistance patterns, the careful knowledge of risk factors for ESBL infection and of factors facilitating adverse outcome, giving attention to local epidemiology, can improve the efficacy of empirical treatment protocols. The aim of this review is to focus on the main characteristics of BSIs caused by ESBL-producing Enterobacteriaceae, with particular emphasis on risk factors for these infections and factors related to mortality.

Detecting risk and predicting patient mortality in patients with extended-spectrum β-lactamase-producing Enterobacteriaceae bloodstream infections

https://repositorio.udes.edu.co/bitstream/001/3413/5/Risk%20factors%20for%20health%20care%e2%80%93associated%20infection%20in%20hospitalized%20adults%20Systematic%20review%20and%20meta-analysis.pdf

Risk factors for health care-associated infection in hospitalized adults: Systematic review and meta-analysis.

Estudo de caso-controle, onde os casos foram pacientes com hemocultura positiva para Klebsiella pneumoniae (KP) ou Escherichia coli (EC) produtores de beta lactamase de espectro estendido (ESBL) e os controles foram pacientes com hemoculturas positivas para EC ou KP nao produtores de ESBL foi realizado para avaliar os fatores de risco para producao destas enzimas em infeccoes da corrente sanguinea (ICS). Mortalidade dos pacientes com ICS tambem foi avaliada. Foram incluidos 145 pacientes (81, 59,5% tinham Klebsiella pneumoniae e 64, 44,1% tinham Escherichia coli); 51 (35,2%) isolados eram produtores de ESBL e 94 (64,8%) eram nao produtores. Quarenta e cinco (55,6%) isolados de K. pneumoniae e somente seis (9,4%) isolados de E. coli eram produtores de ESBL. Analise multivariada mostrou que exposicao recente a piperacilina-tazobactam (OR ajustado [aOddsRatio] 6,2; 95% Intervalo de Confianca [IC] 1,1-34,7) foi fator de risco para infeccao da corrente sanguinea por ESBL. Foi significativamente maior a chance de K. pneumoniae ser um isolado produtor de ESBL do que E. coli o ser (aOR 6,7; 95% CI 2,3-20,2). Nenhuma classe de cefalosporina foi independentemente associada com ESBL-ICS. No entanto, em um modelo secundario considerando todas as oximino-cefalosporinas como variavel unica, foi demonstrada associacao significativa (aOR 3,7; 95% IC 1,3-10,8). Mortalidade total em 60 dias foi significativamente maior entre isolados produtores de ESBL. O achado de piperacilina-tazobactam como fator de risco para producao de ESBL em ICS por KP ou EC requer atencao, uma vez que esta droga tem sido eventualmente recomendada para poupar o uso de cefalosporinas de terceira geracao.

https://www.scielo.br/pdf/rimtsp/v51n4/v51n4a06.pdf

Risk factors for and mortality of extended-spectrum-β-lactamase-producing Klebsiella pneumoniae and Escherichia coli nosocomial bloodstream infections

Aims: To evaluate the prevalence of extended-spectrum beta-lactamases (ESBL) production by Klebsiella pneumoniae and Escherichia coli isolated from hospitalized adult patients and to describe the patient’s clinical characteristics. Methods: Through a cross-sectional study, all charts from adult patients that presented Klebsiella pneumoniae and Escherichia coli bacteremia in Hospital Sao Lucas da PUCRS, from June 2004 to March 2006, were revised. Results: A total of 145 patients were included in the study. Among them, 51 (35.2%) had an isolate of ESBLproducing bacteria. The prevalence of ESBL was higher in Klebsiella pneumoniae (45 isolates, 55.6%) than in Escherichia coli (6 isolates, 9.4% p<0.001). The use of betalactamic antibiotics in the previous 14 days was commonest in the group ESBL-producing (50 pacients, 98%) than in the group no ESBL-producing (15 pacients, 16%); p<0.001. Imipenem was the drug with better in vitro efficacy against ESBL-producing isolates (100%). Conclusions: The study demonstrated a high prevalence of ESBL-producing K. pneumoniae bacteremias. Patients

Prevalência de produção de beta-lactamases de espectro estendido em bacteremias por Klebsiella pneumoniae e Escherichia coli Prevalence of extended-spectrum beta-lactamases in Klebsiella pneumonia and Escherichia coli bacteremia

Gustavo Rossini Augusti

Papers

Risk factors for and mortality of extended-spectrum-β-lactamase-producing Klebsiella pneumoniae and Escherichia coli nosocomial bloodstream infections

Prevalência de produção de beta-lactamases de espectro estendido em bacteremias por Klebsiella pneumoniae e Escherichia coli Prevalence of extended-spectrum beta-lactamases in Klebsiella pneumonia and Escherichia coli bacteremia