Antibiotic resistance surveillance and control in countries of the Mediterranean region

Abstract

Antimicrobial resistance results in a number of substantial adverse outcomes from both healthcare as well as community acquired infectious diseases and negatively impacts mortality, morbidity and economic consequences. Despite this, data about the prevalence of antimicrobial resistance in the south-eastern countries of the Mediterranean has, in the past, b~~n minimal. Besides being few in number, the findings of studies from this region have been difficult to compare as there have been many differences in surveillance ~md lahoratory methodologies. Even less inrolmation was available on the characteristics of antibiotic consumption and infection control practices in this area, despite the known complex relationship between these two factors and the advent of antibiotic resistance. If effective interventions are to be adopted, this basal data are essential. Over its four-year span, the study investigated antimicrobial resistance in nine countries within the southern & eastern Mediterranean region through the collection of comparable and validated antimicrobial resistance data as well as information about antibiotic consumption patterns and infection control initiatives. Resistance in Streptococcus pneumoniae showed significant heterogeneity throughout the region. Highest levels of penicillin non-susceptibility were evident in Algeria and in Egypt. Ilowever no n01lntry nil Istaring was identified, sllggesting that the fantors oontrihllting to resistance in Streptococcus pneul710niae appear to be country rather than region related. An overall total of 5,353 S. aureus isolates were collected for the whole study period, with an overall MRSA proportion of 38%. Except for Tunisia and Morocco, all the participating countries showed an overall prevalence in excess of 30%. MRSA proportions differed extensively between the individual hospitals in the same country. The epidemiology of resistance in E. coli showed the highest regional heterogeneity, especially in the case of resistance to third generation cephalosporins and fluoroquinolones. The most worrying feature to emerge from the E. coli data was evidence of simultaneous multi-resistance to 3rd generation cephalosporins, fluoroquinolones and aminoglycosides. This reached levels of almost 40% in Egypt .. md showed significant evidence of inr,rease in three or the oOlllltrins over the study duration. Antibiotic use in 25 regional hospitals was assessed prospectively for 24 months during the years 2004-2005. The surveillance focused primarily on systemic antibiotics for hospital care

aggregated at the level of the active substance, in accordance with the Anatomic Therapeutic Chemical (ATC) classification. Median total antibiotic use during the study period was 112 Defined Daily Doses (DDD) per hundred bed-days. The most common antibiotic groups prescribed were the extended spectrum and combination peniciliins, first and third generation cephalosporins and quinolones. Overall, the consumption of wider spectrum agents was noted to predominate, with a significant correlation present between levels of use of third generation cephalosporins and carbapenems. Emphasis on wide srer;tn Im agents mlllci exrlain one rossihle far;tor hehinci the cior;llmenteci high rrevalenr;e of resistance identified. A numbel uf slruclured quesliunl1aires luoKing al various aSlJeds of il1fecliol1 C0l1l101 organisation and policies at national and hospital level were undertaken as part of the study. National infection control initiatives were, on the whole, lacking. Only a few countries had official entities responsible for the control of antibiotic resistant organisms, surveillance of nosocomial infections and auditing of hospital infection control activities. Hospitals in the eastern Mediterranean had more established infection control infrastructures. However this did not translate into discernable output, with no significant differences from southern Mediterranean institutions in terms of surveillance activities, the presence of an antibiotic policy and feedback of resistance data to prescribers. The majority of hospitals faced sit! lations of overr;rowciing and regular difficulties due to lack of available isolation beds Hand hygiene was practiced mainly through hand washing but compromised by reliance on hars of soar anci doth towels as well as inmnvenient ciistanr;es of sinks from ratient hecis Progrr.lmmes for better r.lntibiotic: W:ie were on the whole limited in smpe, whilst the influence of the pharmaceutical industry was discerned as being potentially substantial. The information from the infection control questionnaires was converted into numerical scores for various intervention groups and correlated with the respective resistance data for MRSA in the participating hospitals. Statistical analysis suggested a relationship with the levels of overcrowding and isolation capabilities. No association was identified for levels of infection control infrastructure, hand hygiene facilities and antibiotic prescribing initiatives. A further study looking at the impact of overcrowding on MRSA rates in one of the study hospitals showed that peaks of bed occupancy were indeed significantly correlated with corresponding peaks of MRSA with a lag of one to two months. Another correlation study was undertaken to evaluate any links between resistance and consumption patterns within the participating hospitals. This suggested that levels of total antibiotic use were related to MRSA resistance proportions as was total penicillin

consumption. Regression analysis identified combination penicillins, carbapenems, and aminoglycosides as being the positively associated antibiotic groups. Similar analysis for E. coli indicated third generation cephalosporins as the only positively associated antibiotic class.

At the conclusion of the data collection period of the study, a conference on antibiotic resistance in the Mediterranean was organised, with the participation of experts from all the r,OI mtries of the region This rrovirlerl an irleal Ol1l1ortllnity to I mrlertake for,lls gmlll1 discussions and agree recommendations as well as priorities for intervention. Tills was tile flrsL sLudy lo ullllse slandardised l11elllocJoloyies lo cJelelll1ine llle levels of resistance in important pathogens in the south and east Mediterranean as well as evaluate the various drivers of this phenomenon. The results imply that the epidemiological situation in various drug-bug combinations poses significant challenges to health care in the region. The study furthermore suggests that prescribing patterns as well as infection control deficits and pressures of bed occupancy could be major drivers behind the resistance rates. Recommendations have been put forward to address this situation and to improve knowledge through focused research.