Title: This paper is a review of all papers published during 2005-2015 concerning antibacterial resistance in Kuwaiti hospitals as ascertained by a literature search.
Background: Antibiotic resistance in hospitals is a serious problem worldwide, resulting in increases in morbidity, mortality and healthcare costs. This review was intended to derive an up-to-date picture of the situation in Kuwaiti hospitals, with the expectation that this might provide some guidance to authorities and involved medical and scientific workers in these institutions.
Methods and Findings: The PubMed database was searched using the following terms: antimicrobial resistance, antibiotic resistance, antibiotic stewardship, prevalence, epidemiology, mechanism of resistance and Kuwait.
Prevalence of resistant E. coli in Kuwait appears to be very high in Kuwait, with the figure of 77% being quoted in a 1990-2011 review. Resistance was higher in hospital-acquired (HA) urinary infections than in communityacquired (CA), with 2007 figures for cefotaxime being 17% in CA and 26% in HA and for gentamicin 15% and 26%. A 2010 analysis covering eight hospitals reported a range of 7.5% to 29% for third generation cephalosporin resistance and 14% to 40% for ciprofloxacin resistance. A 2002-2005 study found a prevalence of 11.7% ESBL-producing E. coli at one hospital, while figures for another hospital were 62%. The major strain of ESBL has been CTX-M-15 (90% of ESBL in a 2005-2006 study; 65.5% in a 2008 analysis). Carbapenem resistance was reported in E. coli in 2011.
Resistance in K. pneumonia is also prevalent in Kuwait, with a figure of 36.2% in the 1990-2011 review. A 2002-2005 study found 13.3% of clinically significant isolates from blood cultures to be ESBL-producing K. pneumoniae. At another hospital in 2010, 82.1% of K. pneumonia isolates were ESBL-producers. The predominant ESBL has again been CTX-M-15 (91% of ESBL in a 2005-2006 study). Outbreaks due to this clone were recorded in 2006 and 2008. The first reported finding of an OXA-48-producing K. pneumoniae (which hydrolyses carbapenems as well as penicillins) from the Arabian Peninsula was from a Kuwaiti patient in 2011. In the same year, the finding of a qnrA gene (conferring fluoroquinolone resistance) among ESBL-producing K. pneumoniae was first reported. A recent study reported qnr genes in 15.6 % of isolates from three major Kuwaiti hospitals.
The 1990-2011 literature survey revealed a comparatively low prevalence of 16.7% of resistance in A. baumannii. In the 2005-2007 survey of uropathogens, while resistance to amoxicillin/clavulanic acid increased from 54% to 77% in CA and 76% to 86% in HA, to cefotaxime from 65% to 88% in CA and 81% to 95% in HA, resistance to amikacin decreased from 12% to 4% in CA and 40% to 27% in HA, to ciprofloxacin from 15% to 4% in CA and 67% to 35% in HA, to cotrimoxazole from 12% to 8% in CA and 56% to 19% in HA, to gentamicin from 12% to 4% in CA and 57% to 22% in HA, and to piperacillin/tazobactam from 12% to 8% in CA and 55% to 32% in HA. A 2006-2007 outbreak of a carbapenem-resistant A. baumannii in an ICU unit was controlled with tigecycline but a 2011 study showed 13.6% resistance to tigecycline. Multidrug- resistant (MDR) A. baumannii isolates are frequently carbapenemase producers (42.6% in a 2012 study). The diversity of such isolates is shown by the detection of 20 different sequence types in an analysis of 33 MDR isolates in a major hospital from 2011 and 2012, but bla (OXA-23) has become dominant, not only in Kuwait (85% in this series) but also through the Gulf Cooperation Council states (107 of 117 isolates in a 2011-2013 study).
CTX-M-15 type ESBL has also been documented in both S. enterica serotype typhi and nontyphoid Salmonella (2008), while the gyrA gene was found in S. enterica serotypes typhi and paratyphi A in 2010.
An analysis of 1,846 S. aureus isolates from 13 Kuwaiti hospitals during 2005 found 32% of these to be MRSA. Two outbreaks of MRSA in neonatal units in 2007 and 2011 were due to unusual strains not found in other hospitals, possibly indicating independent acquisition, especially given the diverse genetic backgrounds found in the latter instance.
Resistance prevalence in S. pneumoniae in Kuwait is very high, varying from 64% in one hospital to 54.5% in another.
Conclusions: Resistance is obviously a serious problem in Kuwaiti hospitals. This review gives some idea of the scope of the problem but there are many gaps and some anomalies. Some trends are apparent but the overall impression is of a constant state of flux. The extent to which the findings can be generalised to any particular hospital is limited. These factors make constant surveillance (including by molecular methods) by each hospital, as well as nationally, imperative. This, combined with well-instituted antibiotic stewardship, will assist in lessening the impact of resistance on morbidity, mortality and healthcare costs.
Abdullmonem A Ramadhan, Yousef Noori Alrefaei