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.

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.

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.

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.

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.

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.

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.

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.

Prevalence and characteristics of Streptococcus pneumoniae "putative serotype 6E" isolates from Asian countries.

The prevalence, antimicrobial susceptibility, and genotypes of Streptococcus pneumoniae "putative serotype 6E" isolates from Asian countries were investigated. A total of 244 S. pneumoniae serogroup 6 isolates obtained from 11 Asian countries were included in this study. Of the 244 serogroup 6 isolates, 101 (41.4%) were typed as "putative serotype 6E," followed by serotypes 6A, 6B, 6C, and 6D (27.0, 20.1, 5.7, and 5.7%, respectively). Multilocus sequence typing revealed that clonal complex (CC) 90, including ST90 and its variants, was the most prevalent clonal group of "putative serotype 6E" isolates (n = 63; 62.4%). CC146 and CC315 were also found frequently in some of the countries. Most of the "putative serotype 6E" isolates showed very high resistance rates against cefuroxime, erythromycin, azithromycin, clarithromycin, clindamycin, and trimethoprim/sulfamethoxazole, probably due to their highly resistant to antimicrobials clone, CC90. Our results indicate that "putative serotype 6E" is prevalent in Asian countries. The clonal dissemination of "putative serotype 6E" isolates was also identified.

A prospective, observational, epidemiological evaluation of the aetiology and antimicrobial susceptibility of acute otitis media in Saudi children younger than 5years of age.

BACKGROUND: Information regarding acute otitis media (AOM) aetiology is important for developing effective vaccines. Here, bacterial aetiology and antimicrobial susceptibility of AOM were determined in young Saudi children. METHODS: Children aged 3-60months with a new episode of AOM, who had not received antibiotics or had received antibiotics for 48-72h but remained symptomatic, were enrolled in this prospective, observational, epidemiological study in Riyadh. Middle ear fluid (MEF) samples were collected by tympanocentesis or from spontaneous otorrhea, and tested for the presence of Streptococcus pneumoniae, Haemophilus influenzae, Streptococcus pyogenes and Moraxella catarrhalis. Antimicrobial susceptibility of the identified pathogens was assessed using E-tests. RESULTS: Between June 2009 and May 2011, 66 children were enrolled. S. pneumoniae was detected in 6 episodes and non-typeable H. influenzae (NTHi) in 8 episodes. Moreover, Staphylococcus aureus, which is an uncommon cause of AOM, was detected in 17 episodes. Pneumococcal serotypes were 7F (n=2), 23F (n=2), 19F (n=1) and 15F (n=1). Susceptibility to cefotaxime was observed in all pneumococcal and H. influenzae isolates, to cefuroxime in 4/6 pneumococcal and 8/8 H. influenzae isolates, and to penicillin in 5/6 pneumococcal isolates. CONCLUSIONS: S. pneumoniae and NTHi were major bacterial contributors for AOM in Saudi children.

Molecular characterization of carbapenem-insensitive Acinetobacter baumannii in Egypt.

OBJECTIVES: This study investigated the prevalence of diverse Ambler class ß-lactamase-encoding genes in 40 carbapenem-insensitive Acinetobacter baumannii isolates collected from two hospitals in Egypt during the period January-March 2012. METHODS: The resistance levels to different groups of antimicrobial agents were determined. PCR was used to detect the different Ambler class ß-lactamases encoding the following genes: blaTEM, blaSHV, blaCTX-M, blaVEB, blaPER, blaGES, blaVIM, blaIMP, blaSIM, blaSPM, blaGIM, blaNDM, blaADC, blaOXA-23, blaOXA-24, blaOXA-51, and blaOXA-58. ISAba1 and int1 were detected by PCR. RESULTS: The isolates were 100% resistant to amoxicillin-clavulanate, aztreonam, cefepime, cefotaxime, and ceftazidime. Of the isolates, 5% were resistant to colistin, 45% to amikacin, 70% to imipenem, and 85% to ciprofloxacin. The blaADC- and blaOXA-51-like genes were detected in the entire collection. The prevalences of blaOXA-23, blaOXA-24, and blaOXA-58 were 50%, 7.5%, and 5%, respectively. However, the prevalences of blaTEM-, blaPER-, and blaGES-like genes were 87.5%, 55%, and 27.5%, respectively. SHV, CTX-M, VEB, KPC, and MBL encoding genes were not detected. The ISAba1 was found upstream to blaOXA-51, blaOXA-23, and blaADC in 85%, 80%, and 50%, respectively. Of note, 45% (18/40) of the isolates co-produced extended-spectrum ß-lactamases (PER and GES) and carbapenemases (OXA-23 and OXA-58). CONCLUSIONS: The blaADC-, blaTEM-, blaPER-, blaOXA-23-, and blaGES-like genes were found to be the most prevalent types of ß-lactamase-encoding gene in A. baumannii collected from Egypt. A high level of carbapenem resistance is mediated by blaOXA-23, blaOXA-24, and blaOXA-58 (minimum inhibitory concentration (MIC) 32 to >256µg/ml), and a low level of carbapenem resistance is mediated by blaGES (MIC 4-16µg/ml) and by up-regulation of ISAba1-OXA-51 (MIC 1-4µg/ml). Class B MBL was not identified to play a role in carbapenem resistance in A. baumannii isolates from Egypt.

Prevalence and antimicrobial resistance among Gram-negative pathogens in Saudi Arabia.

Antimicrobial resistance among Gram-negative bacteria is a worldwide problem, including in the Kingdom of Saudi Arabia, with major concerns regarding Pseudomonas aeruginosa, Acinetobacter baumannii, and Enterobacteriaceae. Although over half of the isolates of P. aeruginosa remain susceptible to carbapenems, quinolones, and aminoglycosides in most reports from Saudi Arabia, resistance is on increase, with a worrying high prevalence of multidrug resistance. Ceftazidime, ciprofloxacin, and aminoglycosides remain active against A. baumannii isolates in some studies from the Kingdom, but recent data suggest increased resistance. Carbapenems are now the treatment of choice for Acinetobacter infections but their activity too is being eroded. Among Enterobacteriaceae, Escherichia coli, Klebsiella pneumoniae, and Enterobacter spp. are the most clinically relevant species. Rates of extended-spectrum beta-lactamase (ESBL) production by these species vary among studies but are generally high in Saudi Arabia, with many ESBL-producing isolates multiresistant to other agents, except carbapenems and nitrofurantoin. A similar pattern is seen for Klebsiella, although with more resistance to quinolones, aminoglycosides, and to nitrofurantoin than in E. coli. Enterobacter is commonly resistant to penicillins, monobactams, and cephalosporins but mostly susceptible to carbapenems. Carbapenemases are beginning to emerge in Enterobacteriaceae.

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.

Characterization of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae from Riyadh, Saudi Arabia.

The objectives of this study were to determine the prevalences, genotypes, and clonal relationships of extended-spectrum beta-lactamase (ESBL)-producing strains in 98 Klebsiella pneumoniae isolates from Riyadh. The prevalence of ESBLs in these strains was 37·75%. All isolates that were confirmed to have ESBLs were completely resistant to amoxicillin/clavulanate, aztreonam, cefotaxime, ceftazidime, cefoxitin, and gentamicin and were susceptible to tigecycline, colistin, and imipenem. In total, 16·6, 77, and 91·6% of isolates were resistant to amikacin, ciprofloxacin, and piperacillin/tazobactam, respectively. The prevalences of isolates producing the beta-lactamases SHV, CTX-M, and TEM were 91·9, 86·5, and 54·05%, respectively. The most frequent ESBL gene detected was blaCTX-M-15, which was observed in 75% of isolates. Other frequent ESBL genes were blaSHV-12 (29·73% of isolates) and blaSHV-5 (5·4% of isolates); additionally, blaCTX-M-3, blaCTX-M-27, blaCTX-M-57, and blaCTX-M-82 were each detected in one isolate. Pulsed-field gel electrophoresis (PFGE) analysis revealed the presence of diverse and unrelated clones. The high prevalence of ESBL producers among the strains examined in our study was not due to the spread of a single clone of bacteria. Clone A was detected in six isolates, indicating intra-hospital spread. Our study documented a high prevalence of the CTX-M-15 product in K. pneumoniae and demonstrated that SHV-12 was also highly prevalent. This study represents the first report of CTX-M-3, CTX-M-27, CTX-M-57, and CTX-M-82 beta-lactamases in K. pneumoniae isolates from Saudi Arabia.

National surveillance of antimicrobial resistance among Gram-positive bacteria in Saudi Arabia.

BACKGROUND: Antimicrobial-resistant Gram-positive bacteria are important causes of serious infections. METHODS: Between January and December 2009, we examined clinical Gram-positive isolates from 24 hospitals across Saudi Arabia. RESULTS: Among the 13750 isolates, Staphylococcus aureus (62.3%) was the commonest, followed by non-group A beta-haemolytic streptococci (14.8%), group A beta-haemolytic streptococci (7.1%), coagulase-negative staphylococci (6.6%), pneumococci (6.0%), and enterococci (3.1%). Resistance rates were high among S. aureus (methicillin-resistant S. aureus: 32%), coagulase-negative staphylococci (oxacillin: 63%) and pneumococci (penicillin G: 33%; erythromycin: 26%; ceftriaxone: 11%); low among enterococci (vancomycin: 1%) and among beta-haemolytic streptococci. Resistance rates varied between regions, but comparison was complicated by differences in antibiotics tested. Many relevant antibiotics were tested against few isolates (e.g. ampicillin, vancomycin, and high-level gentamicin versus enterococci) while unhelpful tests were widely performed (e.g. cefotaxime, ceftriaxone, and imipenem versus staphylococci. CONCLUSION: Resistance is widespread in staphylococci and pneumococci, but not enterococci and beta-haemolytic streptococci in Saudi Arabia. Rationalization of antibiotic panels tested is urgently needed.