Diversity of Molecular Mechanisms Conferring Carbapenem Resistance to Pseudomonas aeruginosa Isolates from Saudi Arabia.

Background. This study described various molecular and epidemiological characters determining antibiotic resistance patterns in Pseudomonas aeruginosa isolates. Methods. A total of 34 carbapenem-resistant P. aeruginosa clinical isolates were isolated from samples collected at a tertiary hospital in Riyadh, Saudi Arabia, from January to December 2011. Susceptibility testing, serotyping, molecular characterization of carbapenem resistance, and pulsed-field gel electrophoresis (PFGE) were performed. Results. All isolates were resistant to ceftazidime, and more than half were highly resistant (minimum inhibitory concentration (MIC) > 256 mg/L). Fifteen isolates had MIC values ≥64 mg/L for any of the carbapenems examined. Vietnamese extended-spectrum ß-lactamase (VEB-1) (n = 16/34) and oxacillinase (OXA-10) (n = 14/34) were the most prevalent extended-spectrum ß-lactamase and penicillinase, respectively. Verona imipenemase (VIM-1, VIM-2, VIM-4, VIM-11, and VIM-28) and imipenemase (IMP-7) variants were found in metallo-ß-lactamase producers. A decrease in outer membrane porin gene (oprD) expression was seen in nine isolates, and an increase in efflux pump gene (MexAB) expression was detected in five isolates. Six serotypes (O:1, O:4, O:7, O:10, O:11, and O:15) were found among the 34 isolates. The predominant serotype was O:11 (16 isolates), followed by O:15 (nine isolates). PFGE analysis of the 34 carbapenem-resistant P. aeruginosa isolates revealed 14 different pulsotypes. Conclusions. These results revealed diverse mechanisms conferring carbapenem resistance to P. aeruginosa isolates from Saudi Arabia.

The transferability of blaOXA-23 gene in multidrug-resistant Acinetobacter baumannii isolates from Saudi Arabia and Egypt.

Carbapenem-resistant Acinetobacter spp. have been increasingly reported worldwide including Saudi Arabia and Egypt. We examined 64, non-repetitive, Acinetobacter baumannii isolates collected in 2013 and 2014 from four different medical centres (two from Saudi Arabia and two from Egypt). All the isolates were resistant to ceftazidime and ciprofloxacin. The intI1 harbouring blaGES-11 and aac-6'-1b was detected in 19% (n=12) of the isolates. ISAba1 over-expression of blaADC gene was observed in 65% (n=42) of isolates. Of all the isolates 19% (n=12) had ISAba1 upstream of the blaOXA-51-like gene, 69% (n=44) carried the blaOXA-23 gene within the Tn2006 structure, 8% (n=5) had blaOXA-24-like gene and 9% (n=6) harboured either blaVIM-2 or blaNDM-1 gene. Eighty nine percent (n=57) of isolates were resistant to imipenem and had an MIC of ≥8mg/L. Pulsed-field gel electrophoresis (PFGE) typing revealed the presence of 23 different PFGE. Three PFGE types were very widespread, ST236 (CC104) (PFGE type 1, n=15), ST208 (CC92) (PFGE type 2, n=10), ST884 (CC unassigned) (PFGE type 3, n=7) in and across all four medical centres. The blaOXA-23 gene was found to be present on a 60kb transferable plasmid in both PFGE type 1 and 2 but was absent in PFGE type 3. This is the first study to report on the emergence of ST236 in Saudi Arabia and Egypt, and spread of distinct carbapenem resistant A. baumannii clones belonging to ST884, ST945 and ST1096 in Saudi Arabia.

Molecular characteristics of extended-spectrum ß-lactamase-producing Escherichia coli in Riyadh: emergence of CTX-M-15-producing E. coli ST131.

BACKGROUND: The prevalence of extended-spectrum ß-lactamase-producing Escherichia coli (ESBL-EC) has increased recently. The aim of this study was to further characterise and to assess the occurrence of ESBL-EC in Riyadh, to use pulsed field gel electrophoresis (PFGE) typing to investigate the epidemiology of ESBL-EC and to determine the prevalence of ST131 in ESBL-EC. METHODS: A total of 152 E. coli isolates were collected at a tertiary hospital in Riyadh from September 2010 to June 2011. Genotypic and phenotypic methods were used to characterise ESBLs. PFGE was used to determine genetic relatedness. Detection of ST131 and CTX-M-like ESBLs was performed using real-time PCR. RESULTS: Of 152 strains, 31 were positive for ESBLs by phenotypic methods. The blaCTX-M-15 gene was highly prevalent (30/31 strains, 96.77%) among the 31 ESBL-positive E. coli strains. The blaCTX-M-27 gene was detected in one strain. Twenty (64.5%) out of 31 of ESBL-EC were ST131. PFGE revealed 29 different pulsotypes. CONCLUSIONS: Our study documented the high prevalence of ESBLs in E. coli isolates, with CTX-M-15 as the predominant ESBL gene. ST131 clone producing CTX-M-15 has a major presence in our hospital. The high prevalence of CTX-M producers was not due to the spread of a single clone. To the best of our knowledge, this study represents the first report of CTX-M-15 and CTX-M-27 ß-lactamases and the detection of the ST131 clone in Saudi E. coli isolates.

Changing trends in antimicrobial resistance and serotypes of Streptococcus pneumoniae isolates in Asian countries: an Asian Network for Surveillance of Resistant Pathogens (ANSORP) study.

Antimicrobial resistance in Streptococcus pneumoniae remains a serious concern worldwide, particularly in Asian countries, despite the introduction of heptavalent pneumococcal conjugate vaccine (PCV7). The Asian Network for Surveillance of Resistant Pathogens (ANSORP) performed a prospective surveillance study of 2,184 S. pneumoniae isolates collected from patients with pneumococcal infections from 60 hospitals in 11 Asian countries from 2008 to 2009. Among nonmeningeal isolates, the prevalence rate of penicillin-nonsusceptible pneumococci (MIC, ≥ 4 µg/ml) was 4.6% and penicillin resistance (MIC, ≥ 8 µg/ml) was extremely rare (0.7%). Resistance to erythromycin was very prevalent in the region (72.7%); the highest rates were in China (96.4%), Taiwan (84.9%), and Vietnam (80.7%). Multidrug resistance (MDR) was observed in 59.3% of isolates from Asian countries. Major serotypes were 19F (23.5%), 23F (10.0%), 19A (8.2%), 14 (7.3%), and 6B (7.3%). Overall, 52.5% of isolates showed PCV7 serotypes, ranging from 16.1% in Philippines to 75.1% in Vietnam. Serotypes 19A (8.2%), 3 (6.2%), and 6A (4.2%) were the most prominent non-PCV7 serotypes in the Asian region. Among isolates with serotype 19A, 86.0% and 79.8% showed erythromycin resistance and MDR, respectively. The most remarkable findings about the epidemiology of S. pneumoniae in Asian countries after the introduction of PCV7 were the high prevalence of macrolide resistance and MDR and distinctive increases in serotype 19A.

Antimicrobial resistance among non-fermenting Gram-negative bacteria in Saudi Arabia.

OBJECTIVES: Non-fermentative Gram-negative bacilli (non-fermenters) can cause serious healthcare-associated infections and are often resistant to multiple antibiotics. We examined resistance rates among these bacteria from different regions of Saudi Arabia. METHODS: A cross-sectional study between January and December 2009 examined 8908 clinical non-fermenters from 24 hospitals across Saudi Arabia. Susceptibility testing was monitored to ensure compliance with CLSI guidelines, but the antibiotics tested were at the hospitals' discretion. RESULTS: Out of the 8908 non-fermenters, most were Pseudomonas aeruginosa (72.9%), followed by Acinetobacter baumannii (25.3%) and Stenotrophomonas maltophilia (1.8%). Resistance rates among P. aeruginosa were: polymyxin B, 2.2%; imipenem, 15.9%; ciprofloxacin, 22.0%; amikacin, 22.9%; and gentamicin, 31.2%. Resistance rates among A. baumannii were: imipenem, 5.4%; polymyxin B, 13.2%; ciprofloxacin, 64.0%; trimethoprim/sulfamethoxazole, 73.8%; amikacin, 76.9%; and gentamicin, 77.8%. Resistance rates among S. maltophilia were: polymyxin B, 6.9%; trimethoprim/sulfamethoxazole, 20.5%; and ciprofloxacin, 38.9%. There was major variation in resistance rates between geographical regions. CONCLUSIONS: Resistance rates among non-fermenters were high in Saudi Arabia and were variable among regions.

The Epidemiology of Invasive Meningococcal Disease in the Kingdom of Saudi Arabia: A Narrative Review with Updated Analysis.

Reducing invasive meningococcal disease (IMD) through MenACWY immunization is a critical healthcare strategy in the Kingdom of Saudi Arabia (KSA). Robust IMD surveillance is essential to help assess the need for additional immunization initiatives in target populations. This is particularly important in KSA, where mass gatherings accompanying Hajj/Umrah pilgrimages have been associated with IMD outbreaks within the local KSA population, and subsequent intercontinental spread via returning pilgrims. This narrative review of the published literature describes the changing epidemiology of IMD in KSA to provide a perspective on the impact of current immunization strategies and potential gaps. As recent published surveillance data are lacking, we also evaluated publicly reported data from the KSA Ministry of Health (MoH) for 2012-2019 to inform more recent IMD trends. Between 1995 and 2011, national surveillance data indicate that 1103 IMD cases were reported in KSA: 60% in 2000-2001, involving two (mainly MenW) outbreaks involving KSA citizens/residents and pilgrims focused in Mecca and Medina. Across 2002-2011, 184 cases of IMD were reported, with a higher proportion occurring in KSA citizens/residents, and with less focus within pilgrimage centers than apparent in previous years. Our analysis of MoH data found that, between 2012 and 2019, 44 IMD cases were reported, all in KSA citizens/residents, and chiefly in children or infants. No pilgrimage-associated outbreaks have occurred since 2001. Serogroup data were available for 62.5% of all cases for 2002-2011; MenW (40.0%), MenA (35.7%), and MenB (16.5%). Serogroup data for 2012-2019 remain incompletely reported, and the existing surveillance system could be improved, as some element of underestimation/underreporting of IMD may exist. While existing MenACWY immunization strategies for KSA citizens/residents and visiting pilgrims have been successful in reducing IMD due to specific serogroups, disease due to MenB remains a potential risk, and additional immunization strategies should be considered.

Antimicrobial stewardship capacity and manpower needs in the Asia Pacific.

OBJECTIVES: Antimicrobial stewardship is a strategy to combat antimicrobial resistance in hospitals. Given the burden and impact of antimicrobial resistance in the Asia Pacific, it is important to document capacity and gaps in antimicrobial stewardship programmes (ASP). We aimed to understand existing capacities and practices, and define the resources needed to establish antimicrobial stewardship where it is lacking. METHODS: An anonymous online survey, consisting of questions on antimicrobial control at country, hospital and programme levels, was circulated to healthcare providers in the field of infectious diseases and microbiology through Asian Network for Surveillance of Resistant Pathogens, ReAct Group and the Australasian Society for infectious Diseases. RESULTS: 139 participants from 16 countries or regions completed the survey. The majority of participants were adult infectious diseases physicians (61/139, 43.9%) and microbiologists (31/139, 22.3%). Participants from 7 countries reported that antimicrobials can be obtained without prescriptions. Despite the high percentage (75.5%) of respondents working in large hospitals, only 22/139 participants (15.8%) from Australia, China, Singapore, Taiwan, Thailand and Vietnam reported having more than 10 infectious diseases physicians. Hospital empiric antimicrobial guidelines for common infections were available according to 110/139 (79.1%) participants. Pre-authorisation of antimicrobials was reported by 88/113 (77.9%) respondents while prospective audit and feedback was reported by 93/114 (81.6%). Automatic stop orders and culture-guided de-escalation were reported by only 52/113 (46.0%) and 27/112 (24.1%) respectively. CONCLUSION: The survey reveals a wide range of ASP development in Asia Pacific. Establishing national workgroups and guidelines will help advance antimicrobial stewardship in this diverse region.

Impact of slime dispersants and anti-adhesives on in vitro biofilm formation of Staphylococcus epidermidis on intraocular lenses and on antibiotic activities.

OBJECTIVES: Infectious endophthalmitis has occurred despite the use of antibiotics in irrigating solutions during implantation of intraocular lenses (IOLs). This infection is generally resistant to antibiotic therapy and, therefore, removal of the implant is necessary before eradication of the infection. This study was designed to assess the role of chosen dispersants and anti-adhesives in inhibiting Staphylococcus epidermidis hydrophobicity, adhesion, slime production and subsequently biofilm formation on IOLs. METHODS: The relative activity of several potential slime dispersants and anti-adhesives on slime production, hydrophobicity and the adherence of S. epidermidis to IOLs and the degrees to which their effects enhance antibiotic activities were investigated. RESULTS AND CONCLUSIONS: The MBCs of antibiotics against S. epidermidis strains in a biofilm increased 10-16 times compared with those against bacterial strains in suspension. Addition of slime dispersants or anti-adhesives reversed the susceptibility of the strains in a biofilm to that of bacteria in suspension. Slime production by S. epidermidis strains was significantly diminished by dispersants. Anti-adhesives, hyaluronan, heparin and carpobol 934 exerted less effects on slime production than dispersants. Addition of slime dispersants or anti-adhesives to cell cultures resulted in a significant reduction in bacterial surface hydrophobicity compared with control untreated cultures (at P < 0.001). Reduction of slime production and bacterial surface hydrophobicity led to a marked decrease in the adherence of S. epidermidis to IOLs. Slime dispersants were more effective at reducing bacterial adherence than anti-adhesives. Simultaneous use of antibiotics with slime dispersants or anti-adhesives will exert a more beneficial effect during IOL implantation.

Characterization of carbapenemases, ESBLs, and plasmid-mediated quinolone determinants in carbapenem-insensitive Escherichia coli and Klebsiella pneumoniae in Riyadh hospitals.

The main objective of this work was to characterize carbapenemases, extended-spectrum ß-lactamases (ESBLs), and plasmid-mediated quinolone resistance (PMQR) among carbapenem-insensitive Klebsiella pneumoniae and Escherichia coli clinical isolates which were isolated from three hospitals in Riyadh. Thirty-one carbapenem-insensitive isolates (21 K. pneumoniae and 10 E. coli) were recovered from March 2014 to May 2014. Susceptibility testing and phenotypic detection tests were used to characterize the classes of ß-lactamases. PCR assays were performed for the detection of the genes encoding ESBL (blaCTX-M, blaTEM,blaSHV, and blaOXA-1), carbapenemase (blaKPC,blaGES,blaVIM, blaIMP, blaNDM, and blaOXA-48), and PMQR (qnrA, qnrB, qnrS, aac(6)-Ib-cr, qepA, oqxA, and oqxB) genes. All carbapenem-insensitive isolates were carbapenemase producers, with 41.9% and 58.1% being class B carbapenemases class D OXA-48, respectively. While the prevalence of ESBL producers was 80.6%. The following resistance genes were detected; OXA-48-like (58.1%), NDM-type (41.9%), CTX-M-1-like (77.4%), CTX-M-9-like (9.6%), TEM-1 (74.2%), OXA-1 (54.8%), SHV-1 (4.4%), qnrS (58.1%), qnrB (3.2%), and aac(6)-Ib-cr (51.6%). The predominant carbapenemases in the isolates that had carbapenem MIC≤4µg/ml and MIC≥12µg/ml were blaOXA-48-type and blaNDM-type respectively. CTX-M-1-like and qnrS were the dominant ESBL and PMQR genes, respectively. This is the first report in which qnrS was described in the isolates from Saudi Arabia.

Economic assessment of rotavirus vaccination in Saudi Arabia.

In the Kingdom of Saudi Arabia (KSA), rotavirus universal mass vaccination has been introduced in 2013, however, there is limited information available on the economic benefit and the epidemiological impact of the programme to date. We used a Markov cohort model to evaluate and compare the economic value of rotavirus vaccination with no vaccination in a birth cohort of 562,428 infants. This lifetime analysis considered the societal perspective. Model input was obtained through consensus of local experts after two rounds of evaluation of the proposed estimates. The primary outcome measure was to assess cost-effectiveness and to define the cost-neutrality level reached by comparing vaccination with no vaccination as a function of the price adjustment of the vaccination course. With an assumed vaccine coverage rate of 96%, the already started rotavirus vaccination is expected to reduce the overall burden of rotavirus gastroenteritis by 65% with model exercise, over lifetime. The maximum impact will be seen in rotavirus gastroenteritis-related hospitalizations (93%). Outpatient and emergency visits are shown to decline by 87% each while the occurrence of nosocomial infections, by 78%. Cost neutrality is reached if the vaccine price per course is less than SAR 178.20 at steady state. Rotavirus vaccination should be recommended in KSA given the important clinical impact the vaccine can have and the good value for money it can obtain.

Detection of blaOXA-23-like and blaNDM-1 in Acinetobacter baumannii from the Eastern Region, Saudi Arabia.

Acinetobacter baumannii is currently considered as one of the most common successful pathogens in the healthcare system due to its ability to quickly develop resistance. Ten carbapenem-resistant A. calcoaceticus-baumannii complex were isolated from the eastern region, Saudi Arabia in 2014. All isolates were resistant to ciprofloxacin, however, 8 of 10 isolates were tigecycline resistant. Susceptibility test was also carried out for three aminoglycosides, resistance to gentamicin was 80%, amikacin was 90%, and tobramycin was 50%. Colistin susceptibility was seen in all isolates. The 10 isolates harbored blaOXA-23-like and ISAba1 and 9 of them also carried blaADC. Three isolates of 10 harbored blaNDM-1 coding for NDM metallo-ß-lactamase (MBL) with coexistence of blaADC together with either blaGES or blaTEM or both. Those three isolates exhibited negative Etest MBL screening test. Pulsed-field gel electrophoresis revealed the high clonal variability of the isolates, although two isolates were indistinguishable. The risk of dissemination of carbapenem resistance through presence of ISAba1 upstream of OXA-23-like in all isolates raises the concern about emergence of higher carbapenem prevalence rates in the future in our region. This study also demonstrated the importance of molecular surveillance to provide accurate and reliable data about the resistance rates of A. baumannii. Finally, the high incidence of NDM-1 among our isolates requires a routine surveillance to monitor the future prevalence of this enzyme in the region.

First Detection of GES-5 Carbapenemase-Producing Acinetobacter baumannii Isolate.

This study was conducted to investigate the molecular epidemiology of resistance in Acinetobacter baumannii isolates collected at a hospital in Riyadh, Saudi Arabia, from January through December 2010. Twenty-seven A. baumannii were highly resistant (MIC90 > 256 µg/ml) to ceftazidime, cefepime, and aztreonam. Imipenem resistance was seen in 24 isolates, of which 18 had an minimum inhibitory concentration (MIC) >32 µg/mL. Ciprofloxacin, gentamicin, and amikacin resistance was found in 93%, 52%, and 37% of all the isolates, respectively. Moreover, 8 (30%) isolates showed colistin resistance, and 15 (56%) were found to have MICs ≥4 µg/mL for tigecycline. The frequency of ADC, GES-1, GES-11, and GES-5 were 96.3% (n = 26), 18.5% (n = 5), 11% (n = 3), and 3.7% (n = 1), respectively. OXA-23 was found in 63% (n = 17) of the isolates; ISAba1 was found upstream of OXA-23 in 16. OXA-24/40 was detected in only one strain. Multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) analysis revealed that the 27 strains were distributed in 8 sequence types (STs) and 16 clonal pulsotypes (A-P). Five singleton STs were identified, including ST15 and ST113-ST116. The emergence of multidrug-resistant A. baumannii is becoming a major concern in Saudi Arabia. Metallo-ß-lactamases have no role in carbapenem resistance in this collection. The spread of OXA-23 in our strains occurred across different STs and pulsotypes, unlike what has been observed in many other countries. PFGE typing was more discriminatory than MLST. The high frequency of colistin and tigecycline resistance found in the isolates calls for continuous monitoring. This study describes the first identification of GES-5 conferring carbapenem resistance in A. baumannii.

Fecal Colonization with Extended-Spectrum Beta-Lactamase and AmpC-Producing Escherichia coli.

Background. Extended-spectrum ß-lactamases (ESßLs) and AmpC ß-lactamases cause ß-lactam resistance in Escherichia coli. Fecal colonization by ESßL- and/or AmpC-positive E. coli is a source of nosocomial infections. Methods. In order to investigate inpatient fecal colonization by ESßLs and AmpC, antibiotic sensitivity tests were conducted and minimum inhibitory concentrations (MICs) were determined using the disk diffusion method and E-test, respectively. Characterization of ESßL and AmpC was performed using E-test strips, and a set of PCRs and DNA sequence analyses were used to characterize the ESßL and AmpC genes. Results. The whole collection of E. coli isolates (n = 50) was sensitive to imipenem, tigecycline, colistin, and fosfomycin, while 26% of the isolates showed reduced susceptibility to ceftazidime (MIC ≥ 4 µg/mL). ESßL was phenotypically identified in 26% (13/50) of cases, while AmpC activity was detected in two ESßL-producing E. coli isolates. All ESßL-producing E. coli were positive for the CTX-M gene, eleven isolates carried bla CTX-M-15, and two isolates carried bla CTX-M-14 gene. Two CTX-M-positive E. coli isolates carried bla CMY-2. Conclusions. The alimentary tract is a significant reservoir for ESßL- and/or AmpC-producing E. coli, which may lead to nosocomial infection.

Epidemiology of invasive pneumococcal disease in Saudi Arabian children younger than 5years of age.

This study evaluated the incidence, serotype distribution, and antimicrobial susceptibility of invasive pneumococcal disease (IPD) in Saudi Arabian children. This multicenter, prospective, clinical surveillance study included children under 5years of age, residents of one of the seven study health areas, who were brought to a study hospital with suspicion of IPD. Bacterial isolates from sterile site samples, collected less than 24h after hospital visit/admission, were identified, serotyped, and tested for antibiotic susceptibility. Between June 2007 and January 2009, 631 episodes of suspected IPD were recorded, and 623 were included in the analysis. One child (0.2%) had previously received one dose of a pneumococcal vaccine. Forty-seven episodes were positive for Streptococcus pneumoniae and three for Haemophilus influenzae. The incidence of confirmed IPD cases was estimated to be 2.5-21.6 per 100,000 children (<5years). Among the 46 S. pneumoniae isolates serotyped and tested for antibiotic susceptibility, the most common serotypes were 5 and 23F (20% each), 6B (17%), and 1 and 14 (11% each). Sixty-three percent of isolates were multidrug-resistant. Vaccination of Saudi Arabian children with expanded-coverage conjugate pneumococcal vaccines containing serotypes 1 and 5 could have a substantial impact to prevent IPD in this population.

Genetic Characterization of Staphylococcus aureus Isolated from Retail Meat in Riyadh, Saudi Arabia.

Limited data exist from the Gulf Cooperation Council states on the prevalence and population dynamics of Staphylococcus aureus colonizing livestock or contaminating retail meat. This study was designed to determine the presence and genetic characteristics of Staphylococcus aureus isolated from raw retail meat sold in Riyadh, Saudi Arabia. Over a period of 9 months, different raw retail meat types were aseptically processed using the double broth enrichment technique, characteristic colonies from chromogenic and mannitol salt agar were further identified using conventional methods. Susceptibility to 9 antibiotics was determined using the disc diffusion technique. Interpretation of inhibition zone was done according to Clinical and Laboratory Standards Institute guidelines. Molecular characterization was carried out using the StaphyType DNA microarray technology. Twenty-five meat samples yielded Staphylococcus aureus isolates. Camel meat had the highest contamination rate with Methicillin resistant Staphylococcus aureus (MRSA) (20%) and Methicillin susceptible Staphylococcus aureus (28%), while poultry meat had the least contamination rate with MRSA (4%). The MRSA isolates were grouped into 4 clonal complexes (CCs) namely CC1-MRSA-IV/SCCfus (n = 2), CC15-MRSA-V/SCCfus (n = 4), CC80-MRSA-IV/PVL+ (n = 5), and CC88-MRSA-IV/PVL+ (n = 2). All CC15-MRSA-V/SCCfus isolates were obtained from camel meat. This is the first study to demonstrate the novel CC15-MRSA-V/SCCfus in retail camel meat. We recommend that surveillance studies should be incorporated in public health and food hygiene programs.

The molecular basis of ß-lactamase production in Gram-negative bacteria from Saudi Arabia.

Resistance to ß-lactams among Gram-negative bacteria is a worldwide issue. Increased prevalence of extended-spectrum ß-lactamase (ESBL)-producers and the dissemination of carbapenem-resistance genes are particularly concerning. ESBL-producing strains are common in the Kingdom of Saudi Arabia, particularly among the Enterobacteriaceae, and carbapenem resistance is on the increase, especially among the non-fermenters. ß-lactamase production is a major mechanism of resistance to these agents and although ß-lactamase-producing strains have been documented in the Kingdom, relatively few reports characterized the molecular basis of this production. Nevertheless, available data suggest that CTX-M (CTX-M-15 in particular) is the predominant ESBL in the Enterobacteriaceae, with SHV also being prevalent in Klebsiella pneumoniae. Carbapenem resistance in the latter is mainly due to OXA-48 and NDM-1. In Pseudomonas aeruginosa, VEB-like enzymes are the most common ESBLs, and VIM is the prevalent metallo-ß-lactamase. OXA-10 extended-spectrum enzymes are also frequent. PER and GES ESBLs have been reported in Acinetobacter baumannii, and oxacillinases (OXA-23 in particular) are the dominant carbapanamases in this species.

Characterization of Carbapenem-Resistant Enterobacteriaceae with High Rate of Autochthonous Transmission in the Arabian Peninsula.

To establish the role of local transmission versus possible pathogen import due to previous foreign exposure in infections caused by carbapenem non-susceptible Enterobacteriaceae in the Arabian Peninsula, 200 independent isolates collected in 16 hospitals of Saudi Arabia, Kuwait, Oman and the United Arab Emirates were studied. All strains were multidrug resistant; 42.5% of them also qualified as extremely drug resistant. The frequency of various carbapenemases varied according to the participating countries, but in the collection, as a whole, blaNDM-1 was the most frequently encountered carbapenemase gene (46.5%) followed by blaOXA-48-like gene (32.5%). A comparatively high rate (8.9%) of multi-clonal strains carrying both blaNDM and blaOXA-48-like genes in the United Arab Emirates, representing the most resistant subgroup, was encountered. No KPC-expressing isolates were detected. Three major clones of blaNDM-1 carrying Klebsiella pneumoniae of ST152 (n = 22, Saudi Arabia), ST14 (n = 7, United Arab Emirates) and ST147 types (n = 9, Oman) were identified, the latter two clones carrying similar, but not identical HI1b incompatibility type plasmids of >170 kb. While from 78.6% of the cases with documented foreign hospitalization blaNDM positive strains were isolated, these strains formed only 25.6% of all the isolates expressing this enzyme. In fact, 56.8% of the NDM, 75.7% of OXA-48-like and 90.9% of VIM positive strains were recovered from patients without documented foreign exposure, neither in the form of travel or prior hospitalization abroad, suggesting a high rate of autochthonous infections. This, considering the extensive links of these countries to the rest of the world, predicts that trends in the local epidemiology of carbapenem resistant strains may increasingly affect the spread of these pathogens on the global scale. These results call for improved surveillance of carbapenem resistant Enterobacteriaceae in the countries of the Arabian Peninsula.

Impact of travel on international spread of antimicrobial resistance.

Antimicrobial resistance, an escalating problem worldwide, affects a broad range of human diseases. Excessive and inappropriate drug usage is the key driver for the emergence of resistant organisms. Travel, trade and mass migration form an important mode for their spread. The use of molecular biology provides the means of understanding the genesis and spread of the genes for drug resistance. Antimicrobial use in veterinary practice as food additives causes selection of resistant zoonotic pathogens that may spread to humans. Comprehensive surveillance systems should be designed and implemented at local and national levels and a national resistance surveillance database operationalized. There is also need for better regulation of the use of antibiotics and education of the medical fraternity, veterinarians and the public in the appropriate use of antimicrobials.

Guidelines for the management of community-acquired pneumonia in Saudi Arabia: a model for the Middle East region.

Worldwide, community-acquired pneumonia (CAP) is a common respiratory tract infection and is now a growing public health concern in Saudi Arabia. In an effort to simplify treatment regimens to aid the practitioner, empirical treatment guidelines for CAP have evolved across the international medical community, reducing the number of antibiotics used and improving outcomes. Saudi Arabia and the surrounding region have no such consensus guidelines and this document aims to redress this lack. The potential impacts of developing and implementing CAP treatment guidelines in Saudi Arabia, which are new to the Kingdom, will be examined. Widespread adoption of these SACAP guidelines could lead to nationwide reductions of antibiotic resistance and improvement of clinical outcomes. Ultimately, Kingdomwide uniformity of treatment algorithms provides a foundation for both database generation and valuable outcomes of research in the future.

Streptococcus pneumoniae in Saudi Arabia: antibiotic resistance and serotypes of recent clinical isolates.

During 2000, 154 clinical Streptococcus pneumoniae isolates were collected from or through three major hospitals serving the Western, Central, and Eastern regions of the Kingdom of Saudi Arabia. Ninety-one (59.1%) of the 154 isolates were resistant to penicillin with 23 strains (14.9%) highly resistant. Resistance was more prevalent among isolates obtained from patients <10 years of age and from isolates cultured from blood and cerebral spinal fluid. Decreased sensitivity to ceftriaxone, erythromycin, trimethoprim-sulphamethoxazole, and levofloxacin was found in 14.9, 15.6, 9.7, and 1.3% of isolates, respectively. There were no significant differences in the resistance pattern between isolates obtained from patients in the three different geographical areas. Serotypes of 116 isolates revealed the most prevalent types to be (descending order) 4, 3, 19F, 9V, 6A, 19A, 14 and 23F, comprising 75% of all strains typed; 9.5% of isolates were nontypable. S. pneumoniae isolates from Saudi Arabia have become more resistant to penicillin and other antimicrobials over the past 20 years.