Infections caused by extended-spectrum beta-lactamases producing Enterobacteriaceae: clinical and economic impact in patients hospitalized in 2 teaching hospitals in Dakar, Senegal

International audienceBackground: Infections caused by extended-spectrum beta-lactamases producing Enterobacteriaceae (ESBL-E) are of major concern in clinical practice because of limited therapeutic options effective to treat them. Published studies showed that ESBL-E, widely spread in Europe, United States or Asia; are also frequent in Africa. However, the impact of ESBL-E infections is yet to be adequately determined in Sub-Saharan African countries, particularly in Senegal. The aim of our study was to estimate the incidence rate of ESBL-E infections and to assess their clinical and economic impact in Senegal. Methods: Two retrospective cohort studies were conducted in patients hospitalized from April to October 2012. A classic retrospective cohort study comparing patients infected by an Enterobacteriaceae producer of ESBL (ESBL+) and patients infected by an Enterobacteriaceae non-producer of ESBL (ESBL-) was carried out for fatal outcomes. Besides, a retrospective parallel cohort study comparing infected patients by an ESBL+ and ESBL-versus uninfected patients was carried out for the excess LOS analyses. Multivariable regression analysis was performed to identify risk factors for fatal outcomes. A multistate model and a cost-of-illness analysis were used to estimate respectively the excess length of stay (LOS) attributable to ESBL production and costs associated. Cox proportional hazards models were used to assess the independent effect of ESBL+ and ESBL-infections on LOS. Results: The incidence rate of ESBL-E infections was 3 cases/1000 patient-days (95 % CI: 2.4–3.5 cases/1000 patient-days). Case fatality rate was higher in ESBL+ than in ESBL-infections (47.3 % versus 22.4 %, p = 0.0006). Multivariable analysis indicated that risk factors for fatal outcomes were the production of ESBL (OR = 5.7, 95 % CI: 3.2–29.6, p = 0.015) or being under mechanical ventilation (OR = 5.6, 95 % CI: 2.9–57.5, p = 0.030). Newborns and patients suffering from meningitidis or cancer were patients at-risk for fatal outcomes. ESBL production increased hospital LOS (+4 days) and reduced significantly the hazard of discharge after controlling for confounders (HR = 0.3, 95 % CI:0.2–0.4). The additional cost associated with ESBL-production of €100 is substantial given the lower-middle-income status of Senegal. Conclusion: Our findings show an important clinical and economic impact of ESBL-E infections in Senegal and emphasize the need to implement adequate infection control measures to reduce their incidence rate. An antibiotic stewardship program is also crucial to preserve the effectiveness of our last-resort antibiotic drugs

Population structure of clinical Pseudomonas aeruginosa from West and Central African countries.

Pseudomonas aeruginosa (PA) has a non-clonal, epidemic population with a few widely distributed and frequently encountered sequence types (STs) called 'high-risk clusters'. Clinical P. aeruginosa (clinPA) has been studied in all inhabited continents excepted in Africa, where a very few isolates have been analyzed. Here, we characterized a collection of clinPA isolates from four countries of West and Central Africa.184 non-redundant isolates of clinPA from hospitals of Senegal, Ivory Coast, Nigeria, and Central African Republic were genotyped by MLST. We assessed their resistance level to antibiotics by agar diffusion and identified the extended-spectrum β-lactamases (ESBLs) and metallo-β-lactamases (MBLs) by sequencing. The population structure of the species was determined by a nucleotide-based analysis of the entire PA MLST database and further localized on the phylogenetic tree (i) the sequence types (STs) of the present collection, (ii) the STs by continents, (iii) ESBL- and MBL-producing STs from the MLST database.We found 80 distinct STs, of which 24 had no relationship with any known STs. 'High-risk' international clonal complexes (CC155, CC244, CC235) were frequently found in West and Central Africa. The five VIM-2-producing isolates belonged to CC233 and CC244. GES-1 and GES-9 enzymes were produced by one CC235 and one ST1469 isolate, respectively. We showed the spread of 'high-risk' international clonal complexes, often described as multidrug-resistant on other continents, with a fully susceptible phenotype. The MBL- and ESBL-producing STs were scattered throughout the phylogenetic tree and our data suggest a poor association between a continent and a specific phylogroup.ESBL- and MBL-encoding genes are borne by both successful international clonal complexes and distinct local STs in clinPA of West and Central Africa. Furthermore, our data suggest that the spread of a ST could be either due to its antibiotic resistance or to features independent from the resistance to antibiotics

Resistance profile of bacteria isolated from the environment of high-risk departments in Ziguinchor hospitals

Background: The environment of our hospital facilities is colonised by various microorganisms. These microorganisms in general and bacteria in particular are often responsible for nosocomial infections. The occurrence of these infections is linked firstly to the lack of asepsis, secondly to the nature of the colonising bacteria and thirdly to the immune status of the patients. The objective of this study was to evaluate the composition of the bacterial flora and to determine the antibiotic resistance profile of these bacteria. Methods : We proceeded to swab the surface of the work areas (table, bench, trolley, hospital bed, door wrist, gurney, incubator, respirator, etc.).  The swabs were then soaked in a culture broth (Thioglycolate Broth or BT) for 18 to 24 hours before being plated on selective media for identification ; Chapman agar, EMB agar (Eosin Methylen Blue), GSN agar (Blood Agar + nalidixic acid), Sabouraud agar. Results: The isolated bacteria consisted mainly of multidrug-resistant bacteria (MDR). Thus, extended-spectrum beta-lactamase-secreting bacteria represented 5.5% (8 strains) of the isolated bacteria were distributed as follows: Enterobacter spp (25%, n=4) Klebsiella pneumoniae (12.5%, n=2) and Escherichia coli (12.5%, n=2). Among the other BMR, we found Acinetobacter spp (25%, n=4), Pseudomonas aeruginosa (6.25%, n=1) and methicillin-resistant Staphylococcus aureus (18.75%, n=3). Conclusion: Nosocomial infections are nowadays one of the main causes of prolonged hospital stay. The isolated bacteria of medical interest were mainly multidrug resistant bacteria. It is therefore imperative to respect the rules of hygiene during care and to evaluate the composition of the bacterial flora of the services in order to set up a strategic plan to fight against these infections

Characteristics of clinical isolates from West and Central Africa (n = 184), by country.

a<p>Resistance rate or resistance status were defined according to the 2013 recommendations of the European Committee on Antimicrobial Susceptibility Testing (EUCAST, 2013 <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0107008#pone.0107008-European1" target="_blank">[13]</a>). Tic: ticarcillin; Tzp: Pipercillin-tazobactam; Caz: Ceftazidime; Fep: Cefepime; Atm: Aztreonam; Imp: Imipenem; Amk: Amikacin; Tob: Tobramycin; Cip: Ciprofloxacin. Here, all non-susceptible isolates were considered as resistant.</p>b<p>Only isolates with an inhibition diameter around the disk of aztreonam (30 µg) <16 mm were considered as resistant.</p><p>Characteristics of clinical isolates from West and Central Africa (n = 184), by country.</p

Distribution of the STs of clinical isolates of <i>Pseudomonas aeruginosa</i> on a dendrogram built with the data all known STs (<i>n</i> = 1595), broken down by their continent of origin.

<p>The geographical origin of each ST was extracted from the <i>P. aeruginosa</i> MLST database in July 2013 <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0107008#pone.0107008-University1" target="_blank">[11]</a>.</p

Map of Africa showing the four cities included in the study, the number of <i>Pseudomonas aeruginosa</i> clinical isolates, and the localization of ESBL- and MBL-producing isolates.

<p>Map of Africa showing the four cities included in the study, the number of <i>Pseudomonas aeruginosa</i> clinical isolates, and the localization of ESBL- and MBL-producing isolates.</p

Distribution of the STs and CCs of the <i>Pseudomonas aeruginosa</i> containing isolates producing either extended-spectrum β-lactamase or metallo-β-lactamase defined in the following references [5], [28], [45], [46] on a dendrogram built with the data all known STs (<i>n</i> = 1595).

<p>ESBL- and MBL-producers were represented with red spots. See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0107008#pone-0107008-g002" target="_blank">Figure 2</a> legend for the tree construction details. Pink zones surround STs that belong to the same clonal complex.</p