Effect of the introduction of pneumococcal conjugate vaccines on serotype prevalence in Kuwait and Saudi Arabia.

BACKGROUND: Streptococcus pneumoniae infection is a major cause of morbidity and mortality. Although pneumococcal disease burden in Kuwait and Saudi Arabia is considered high, comprehensive surveillance data on pneumococcal conjugate vaccine (PCV) effects are lacking. METHODS: Sterile isolates from patients in Kuwait (2003-2016) and Saudi Arabia (aged ≤5 years, 2000-2010; all patients, 2011-2015) were included. Serotyped isolates were classified by inclusion in the 7-valent (PCV7) or 13-valent PCV (PCV13); isolates of other serotypes were classified as "non-PCV13". Isolate frequency (number of isolates/year) and classification of isolates according to vaccine type were assessed by period (before PCV, after PCV7, and after PCV13 introduction). RESULTS: In Kuwait, the frequency of collected isolates was highest after PCV7 introduction. Decreased frequency of PCV7 serotypes was seen after PCV13 introduction compared with before PCV and after PCV7 introduction. Increased frequency of the 6 additional serotypes in PCV13 and non-PCV13 serotypes was observed after PCV7 introduction with a subsequent decrease in the 6 additional serotypes in PCV13 and non-PCV13 serotypes after PCV13 introduction. The percentage of isolates of vaccine serotypes in Kuwait decreased over time. In Saudi Arabia, the frequency of collected isolates was highest after PCV7 introduction. An increased frequency of PCV7 serotypes was observed after PCV7 introduction, with a further decrease after PCV13 introduction. For the 6 additional serotypes in PCV13, an increased frequency was seen after PCV7 and PCV13 introduction compared to before PCV introduction. For non-PCV13 serotypes, an increased frequency was observed after PCV13 introduction compared to after PCV7 introduction. The percentage of isolates covered by PCV13 serotypes was similar across periods, while a substantial decrease in isolates covered by PCV7 was seen after PCV13 introduction. CONCLUSION: PCVs in Kuwait and Saudi Arabia resulted in decreased frequency of some vaccine serotypes and an emergence of some non-PCV13 serotypes. Further investigation is warranted.

A novel multiplex PCR for molecular characterization of methicillin resistant Staphylococcus aureus recovered from Jeddah, Kingdom of Saudi Arabia.

BACKGROUND: Molecular characterization of staphylococcal cassette chromosome mec (SCCmec) types of methicillin-resistant Staphylococcus aureus (MRSA) is very essential for studying the epidemiology of MRSA. OBJECTIVES: This study reports two multiplex PCR for molecular typing of MRSA collected from Jeddah, Kingdom of Saudi Arabia. MATERIALS AND METHODS: A total of 101 clinical isolates of strains were collected from major hospital laboratories and public health centres, Jeddah, Kingdom of Saudi Arabia during the period from August 2009 to May 2011. All the strains were tested phenotypically by conventional methods and genotypically by a novel multiplex PCR targeting at the same time S. aureus 16S rRNA, Panton - valentine leucocidin (PVL) and mecA resistance genes. All the strains were tested also by multiplex PCR for typing of SCC mec types. RESULTS: All the 101 strains previously identified phenotypically as S. aureus with bacteriological examination were positive for amplification of 756 base pair fragments specific for 16S rRNA of S. aureus. Moreover, all the strains were positive for amplification of 1339 base pair fragments specific for mecA gene, while only 38 strains (37.6%) showed positive amplification of 433 base pair fragments specific for PVL gene. The most predominant SCC mec type among the examined isolates is type V 43 (42.5) followed by SCCmec type III 39 (38.6%). CONCLUSION: The newly modified multiplex PCR is rapid and sensitive method for detection of MRSA. Moreover, the most predominant SCC mec type among the examined isolates from Jeddah, King Saudi Arabia is type V (42.5%), followed by Type III (38.6%).

Characterization of Enterococcus faecium isolates and first report of vanB phenotype-vanA genotype incongruence in the Middle East.

We aimed to characterize the vancomycin genotype/phenotype, carriage of putative virulence genes, and genetic relatedness of Enterococcus faecium isolates in Saudi Arabia. E. faecium isolated from inpatients at our medical center were studied. Sensitivity to ampicillin, linezolid, teicoplanin, quinupristin/dalfopristin, tetracycline, and ciprofloxacin was determined. The presence of van genes and virulence genes for aggregation substance (Asa-1), enterococcal surface proteins (esp), cytolysin (cylA, cylL, cylM), gelatinase (gelE), E. faecium endocarditis antigen (EfaA( fm )), hyaluronidase (hyl), and collagen adhesion (Ace) was assessed. Genetic relatedness was determined by pulsed-field gel electrophoresis (PFGE). Twenty-nine E. faecium isolates were obtained and the majority of isolates (n/N = 22/29) were from stool specimens. PFGE analysis identified eight pulsotypes (A-H) based on 80 % similarities. Isolates were represented in five major pulsotypes: type A (n = 5), type B (n = 3), type D (n = 6), type E (n = 5), and type F (n = 7). All isolates were vanA gene-positive. Thirteen isolates had vanA(+)/vanB(+) genotype. Of these, ten exhibited a vanB phenotype and three had a vanA phenotype. Eight isolates with vanA(+)/vanB(-) genotype exhibited vanB phenotype. Six of these eight isolates belonged to the same pulsotype. All isolates were positive for gelE, esp, and EfaA( fm ) genes. Five were CylA-positive and 24 had the hyl genes. Of the eight isolates harboring a combination of gelE, esp, EfaA( fm ), and hyl genes, five showed vanB phenotype-vanA genotype incongruence. This is the first report of vanB phenotype-vanA genotype incongruent E. faecium in the Middle East region. Molecular typing indicates clonal spread and high occurrence of virulence genes, especially esp genes, associated with epidemic clones.

Distribution of serotypes and antibiotic resistance of invasive pneumococcal disease isolates among children aged 5 years and under in Saudi Arabia (2000-2004).

To determine vaccine coverage of invasive pneumococcal disease (IPD) in Saudi Arabian children aged 5 years and under, 350 IPD isolates were tested for antibiotic susceptibility. Of these 46%, 42% and 12% were penicillin-sensitive, pencillinintermediate, and penicillin-resistant, respectively. Rates of resistance to erythromycin and cefotaxime were 26% and 6%, respectively. The potential serotype coverage of the PCV7 vaccine in Saudi Arabia among children <5 years of age is 62%, and vaccine coverage significantly improved in children <2 years of age, to reach 83% against IPD isolates. PCV7 is expected to have a substantial impact on the burden of invasive and antibiotic-resistant pneumococcal disease in Saudi Arabia.

Emergence and trends of penicillin non-susceptible Streptococcus pneumoniae in Saudi Arabia and Kuwait - perspective and outstanding issues.

For many years in the past Streptococcus pneumoniae was uniformly susceptible to penicillin until the sudden and unexpected emergence of clinical infections caused by penicillin-resistant S. pneumoniae (PRSP) in 1967. Within the following decade, reports of nosocomial and community outbreaks of infections due to PRSP became widespread all over the world. Recent reports suggest that the incidence of resistance rates is rising in many countries although there are geographical variations in the prevalence and patterns of resistance between countries. The problem of antibiotic resistance is further compounded by the emergence of resistance to many beta-lactam antibiotics. The first report of PRSP in Saudi Arabia was in 1991. Barely a year after, PRSP infection was reported in Kuwait in 1992. Since then, studies from various parts of these countries have recorded prevalence rates ranging from 6.2% in Riyadh to 34% in Jeddah and 20% to 56% in neighboring Kuwait. These suggest considerable variation in the prevalence of PRSP in different cities in the Saudi Kingdom and Kuwait. The mechanism of resistance is due to chromosomally mediated alteration of penicillin-binding proteins (PBPs), which are target sites for beta-lactam antibiotics. It would appear that the spread of PRSP strains in Saudi Arabia is driven by the selective pressure created by excessive use and misuse of antimicrobial agents made possible by the easy availability of these agents, often frequently obtainable over the counter. In Kuwait, irrational and misguided use of antibiotics may be the major driving force favoring the spread of PRSP. The serotypes of strains encountered in Saudi Arabia and Kuwait are almost identical, with serotypes 19, 6, 15, 14 and 23 being the most common; together they constitute about 70% of the isolates circulating in these countries. In general, almost 90% of the serotypes included in the 23-polyvalent vaccine are present in the general population. However, a much lower percentage of these serotypes is found in the conjugated vaccines, which are more relevant to our communities. This paper reviews the emergence and the steady increase in the prevalence of penicillin-resistant pneumococcal strains in Saudi Arabia and Kuwait during the last 10 years. It discusses the trends, mechanisms of resistance and factors associated with the emergence, dissemination, and colonization of resistant organisms and suggests options available to clinicians for management of infections due to PRSP.

Rationale for producing evidence-based guidelines for community-acquired pneumonia in the Gulf Corporation Council.

World-wide community-acquired pneumonia (CAP) is a common respiratory tract infection and is now a growing public health concern in the GCC region. Practice guidelines are derived statements which lead to informed clinical decision making. National and regional guidelines have been developed in North America, South America, South Africa and Western Europe to assist practitioners managing patients with CAP and have demonstrated to improve patients outcome. Four years have elapsed since the publication of the Saudi Arabian CAP guideline and notable changes in the area of CAP demand revision of this earlier document. We expanded previous guidelines to a regional level in a number of ways: by incorporating changes in antimicrobial resistance profiles in the region, by considering the regional availability of antibiotics and diagnostic procedures, by including emerging data on new advancements in diagnosis and treatment of CAP and, finally, by adopting an evidence-based approach in grading relevant data. The current document seeks to target primary care physicians who manage most patients with CAP in the GCC region. All available and relevant peer reviewed studies published until June 2007 were considered in the literature review. Based on the strength of the evidence, we graded our recommendations to high-level (Level I), moderate-level (Level II), and low-level (Level III) evidence.

Microbiology of community-acquired pneumonia in the Gulf Corporation Council states.

In spite of advances in microbiological and serological investigations over the last two decades, etiological attribution remains difficult in community-acquired pneumonia (CAP). Even after exhaustive investigation, the etiology of CAP remains unknown in up to 50% of patients. Common pathogens include Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. In addition, several investigators document the importance of atypical pathogens including Mycoplasma pneumoniae, Chlamydophila pneumoniae and Legionella pneumophila in the etiology of CAP in the GCC region. Increasingly, other etiologies, particularly influenza viruses, varicella zoster virus and Mycobacterium tuberculosis, have been recognized as causative pathogens of CAP within the region. Rates of antimicrobial resistance of S. pneumoniae and other pathogens are rising in the Gulf Corporation Council (GCC) region and susceptibility profiles of antibiotics against intracellular pathogens such as Chlamydophila pneumoniae and Mycoplasma pneumoniae are not routinely performed. Injudicious prescribing and over-use of antibiotics drive much resistance. The GCC CAPWG calls for urgent governmental regulations to limit and monitor antibiotic prescription in the GCC region.

Clinical presentation and diagnostic workup for community-acquired pneumonia: the Gulf Corporation Council CAP Working Group consensus statement.

Community-acquired pneumonia (CAP) is diagnosed on the basis of a suggestive history and compatible physical findings and new infiltrates on a chest radiograph. No criteria or combination of criteria based on history and physical examination have been found to be gold standard. With the rise in elderly Gulf Cooperation Council (GCC) residents, CAP is likely to present with non-classical manifestations such as somnolence, new anorexia, and confusion and carries a worse outcome than CAP in their younger counterparts. Tuberculosis should be considered in the differential diagnosis of unresolving CAP in the GCC region. Diagnostic work up depends on severity of CAP, clinical course and underlying risk factors.

Management and prevention strategies for community-acquired pneumonia in the Gulf Corporation Council.

Risk factors identify likelihood and severity of community-acquired pneumonia (CAP) and may allow prognostication. Prognostic factors can focus resources and efforts on those who may need special observation. Several risk assessment tools are used to estimate the severity of CAP and whether these tools can be used to predict outcomes, to determine disposition or even used to determine ICU level of care is hotly under debate. Treating CAP depends on age and comorbidities, as well as local epidemiology and disease severity. The current guidelines for managing CAP categorize patients with CAP into the healthy outpatient, the outpatient with modifying factors or comorbidities, the inpatient with CAP and patients requiring intensive care unit admission. These guidelines took into account regional bacteriology, antibiotic resistance data and available antibiotics to formulate recommendations. Preventive strategies for CAP include the administration of pneumococcal and influenza vaccine in selected populations at risk.

Patterns of macrolide resistance determinants among S. pyogenes and S. pneumoniae isolates in Saudi Arabia.

In the study we characterized the macrolide sensitivity of recent clinical isolates of Streptococcus pyogenes and S. pneumoniae collected from major Saudi Arabian hospitals. Susceptibility testing was performed using standard National Committee for Clinical Laboratory Standards methodology on 335 S. pyogenes and 350 S. pneumoniae isolates. Macrolide resistance mechanism phenotypes were identified using double-disk diffusion. All S. pyogenes were penicillin sensitive, while 6.3% were macrolide resistant, the main mechanism of which was of M phenotype (96%). Approximately 51% of S. pneumoniae were penicillin non-susceptible. Macrolide resistance in S. pneumoniae accounted for 18.8%, the majority of which were M phenotype (91%). Low-level resistance mediated by mef-bearing strains pre-dominated. Newer macrolides, including azithromycin, are still considered drugs of choice for empirical treatment of respiratory infection in such circumstances.

Beta-lactam and macrolide resistance and serotype distribution among Streptococcus pneumoniae isolates from Saudi Arabia.

Three hundred thirty-six clinically significant Streptococcus pneumoniae isolates were collected from laboratories of different hospitals in Riyadh, Saudi Arabia. Most of these isolates were from pulmonary and otitis media (68.2%), and 31.8% were extrapulmonary (blood and CSF). Of the 336 isolates, 44.6% were susceptible to penicillin, and 55.4% were penicillin non-susceptible (35.7% were intermediate and 19.7% were fully resistant). The isolates showed 9.0% resistance to co-amoxiclav, 31.8% to cefuroxime and 39.4% to cefprozil. None of the isolates were resistant to ceftriaxone. Overall macrolide resistance rates were 22.6% to erythromycin, 18.5% to roxithromycin, 17.9% to azithromycin and 17.3% to clarithromycin. Most penicillin non-susceptible pneumococci were of serogroups/types 19 (21.0%), 6 (10.8%), 18 (8.6%), 23 (8.1%) and 14 (7.0%). Serogroups 9, 15, and 1 were found in 5.4%, 4.3%, and 2.2% of the isolates, respectively. Nontypeable strains constituted 6.5%. In exploring the mechanism of resistance to macrolides, 28 of 76 (36.8%) of isolates were erythromycin-resistant due to ribosomal mechanism (all were constitutive type, none were inducible), whereas 48 (63.2%) isolates were resistant due to an efflux mechanism. Good antibiotic control with periodical antibiotic surveillance and appropriate use of pneumococcal vaccine may improve current treatment of pneumococcal infections.

Elucidation of antibiotic effectiveness against Staphylococcus epidermidis during intraocular lens implantation.

The effect of various antimicrobial agents commonly used in irrigating solutions on the hydrophobicity and adherence of Staphylococcus epidermidis ATCC 14990 was investigated. The longest post-antibiotic effect (PAE=3.2 h) was obtained with gentamicin followed by ciprofloxacin (2.7 h), clindamycin (2.2 h), ceftazidime (1.8 h) and vancomycin (1.6 h). The post-antibiotic effect on surface hydrophobicity of cells previously treated with gentamicin, ciprofloxacin, or clindamycin for 120 min resulted in a substantial decrease in affinities to hexadecane (31.4, 28.5 and 27%, respectively) compared with control untreated cells. Less effect was noted with cells previously treated with ceftazidime or vancomycin (20.5 and 15.8%, respectively). Similar but less marked results were obtained when the cells were exposed to antibiotics for 30 or 60 min. The post-antibiotic effect on adherence of cells to both intraocular lenses and to epithelial cells showed that adherence to lenses decreased as the time of exposure to antimicrobial agents increased. Adherence was greatly diminished with cells treated with gentamicin or ciprofloxacin compared with control untreated cells. Adherence was less affected by clindamycin, ceftazidime and vancomycin. The data supported the use of antimicrobial agents in irrigating solution during intraocular surgery, since, reduced adherence (colonization) and might result in a lower incidence of endophthalmitis.

Antibiotic resistance in developing countries.

During the past decade there have been major changes in the susceptibility of bacteria that cause various infections. Resistance to anti-infective agents, including antibiotics, is worldwide, both in developed and developing countries. Almost all bacterial species can develop resistance to anti-infective agents and resistance can readily be transferred among bacteria by transmissible elements (plasmids). Measures to prevent the emergence of resistance must be implemented urgently. A multiplicity of factors drive antibiotic resistance and solutions require the collaboration of governmental agencies, pharmaceutical companies, healthcare providers and consumers. Knowledge of resistance patterns and of the ways by which resistance is overcome is vital to the future of antimicrobial chemotherapy.

Carriage of antibiotic-resistant pneumococci among Asian children: a multinational surveillance by the Asian Network for Surveillance of Resistant Pathogens (ANSORP).

To investigate the nasal carriage of antibiotic-resistant pneumococci by children, anterior nasal swabs were done for 4963 children <5 years old in 11 countries in Asia and the Middle East. In total, 1105 pneumococci isolates (carriage rate, 22.3%) were collected, 35.8% of which were found to be nonsusceptible to penicillin. Prevalence of penicillin nonsusceptibility was highest in Taiwan (91.3%), followed by Korea (85.8%), Sri Lanka (76.5%), and Vietnam (70.4%). Penicillin resistance was related to residence in urban areas, enrollment in day care, and a history of otitis media. The most common serogroups were 6 (21.5%), 23 (16.5%), and 19 (15.7%). The most common clone, as assessed by pulsed-field gel electrophoresis, was identical to the Spanish 23F clone and to strains of invasive isolates from adult patients. Data in this study documented the high rate of penicillin or multidrug resistance among isolates of pneumococci carried nasally in children in Asia and the Middle East and showed that this is due to the spread of a few predominant clones in the region.

Antibiotics in the irrigating solutions reduce Staphylococcus epidermidis adherence to intraocular lenses.

PURPOSE: To investigate the effect of antibiotics in the irrigating solutions on hydrophobicity, slime production and the adherence of Staphylococcus epidermidis to intraocular lenses (IOLs). METHODS: A standard culture of S. epidermidis was incubated with a control phosphate-buffered saline (PBS) or PBS containing vancomycin (20 micrograms/ml) or gentamicin (8 micrograms/ml) or a combination of gentamicin and vancomycin (8 and 20 micrograms/ml, respectively) for 30, 60 and 120 min at 35 degrees C. The bacteria were harvested by centrifugation, and washed with PBS before incubation with IOLs for 1 h. Adhesion of bacterial cells to IOLs was determined by counting the viable cells attached to the lenses. Slime production on IOLs was measured using safranin staining. Hydrophobicity of the control cultures and cultures treated with antibiotics was assayed on the basis of the hexadecane droplet method. RESULTS: Bacterial exposure to antibiotics produced a time-dependent significant decrease in bacterial hydrophobicity and adherence to IOLs compared with the untreated control cells (p < 0.001). Hydrophobicity showed a significant correlation with adherence (r = 0.89, p < 0.001). Gentamicin was significantly more effective than vancomycin, and the synergistic combination of gentamicin and vancomycin was the most effective in reducing bacterial adherence to IOLs, hydrophobicity and slime production. CONCLUSIONS: The use of antibiotics in the irrigating solutions during cataract surgery may be useful in reducing bacterial adherence to IOLs. Further studies are needed to determine the clinical implications of these findings in reducing the incidence of post-operative endophthalmitis associated with IOL implantation.

Penicillin-resistant and -intermediate Streptococcus pneumoniae in Saudi Arabia.

The antibiotic susceptibility was analyzed of approximately 400 consecutive isolates of S. pneumoniae isolated from different regions of Saudi Arabia. Most of these isolates were from respiratory (sputum, otitis, 53.8%), blood/CSF (26.3%) and ophthalmic (20%) specimens. Overall 6.2% of the isolates were penicillin-resistant (MICs > or =2 microg/ml) and 51.2% were -intermediate (MICs 0.1-1 microg/ml). The resistance rates to cefuroxime, clarithromycin and ceftriaxone were 14.9%, 14.8% and 4.5% respectively. Only 3.5% of S. pneumoniae showed resistance to amoxycillin/clavulanic acid. The MICs of all tested antibiotics increased as did the penicillin MICs. Penicillin resistance was significantly associated with resistance to cefuroxime (p<0.001) but not with the others. These data indicate the presence of penicillin and multiple-resistant pneumococci in Saudi Arabia and that these strains can spread among individuals. A greater awareness with extended indications for microbiological diagnosis, antimicrobial susceptibility testing and restrictive prescription of antibiotics are needed.

Reduction of mucoid Staphylococcus epidermidis adherence to intraocular lenses by selected antimicrobial agents.

The effect of low concentrations of various antimicrobial agents on the adherence of mucoid Staphylococcus epidermidis to intraocular lenses was investigated. Adherent growth of S. epidermidis on to polymethylmethacrylate lenses was greatly diminished by ciprofloxacin and clindamycin (>75%), followed by ceftazidime ( approximately 50%) and less affected by gentamicin and vancomycin (<25%) compared to the adherent growth of control untreated cells. The reduction in adherence growth was concentration-dependent and found to be due to the inhibition of slime production since no growth inhibition was observed at the concentrations used. Cell surface hydrophobicity was markedly reduced in parallel to the inhibition of adherence as compared to the control cells. The differential effect of antibiotics on adherence, regardless of their antimicrobial activity, may have a clinical significance in reducing the incidence of postoperative endophthalmitis and intraocular inflammation due to the reduction of cell adherence.