Antibiotic Guidelines for Critically Ill Patients in Nigeria.

BACKGROUND: It is well documented that inappropriate use of antimicrobials is the major driver of antimicrobial resistance. To combat this, antibiotic stewardship has been demonstrated to reduce antibiotic usage, decrease the prevalence of resistance, lead to significant economic gains and better patients' outcomes. In Nigeria, antimicrobial guidelines for critically ill patients in intensive care units (ICUs), with infections are scarce. We set out to develop antimicrobial guidelines for this category of patients. METHODS: A committee of 12 experts, consisting of Clinical Microbiologists, Intensivists, Infectious Disease Physicians, Surgeons, and Anesthesiologists, collaborated to develop guidelines for managing infections in critically ill patients in Nigerian ICUs. The guidelines were based on evidence from published data and local prospective antibiograms from three ICUs in Lagos, Nigeria. The committee considered the availability of appropriate antimicrobial drugs in hospital formularies. Proposed recommendations were approved by consensus agreement among committee members. RESULTS: Candida albicans and Pseudomonas aeruginosa were the most common microorganisms isolated from the 3 ICUs, followed by Klebsiella pneumoniae, Acinetobacter baumannii, and Escherichia coli. Targeted therapy is recognized as the best approach in patient management. Based on various antibiograms and publications from different hospitals across the country, amikacin is recommended as the most effective empiric antibiotic against Enterobacterales and A. baumannii, while colistin and polymixin B showed high efficacy against all bacteria. Amoxicillin-clavulanate or ceftriaxone was recommended as the first-choice drug for community-acquired (CA) CA-pneumonia while piperacillin-tazobactam + amikacin was recommended as first choice for the treatment of healthcare-associated (HA) HA-pneumonia. For ventilatorassociated pneumonia (VAP), the consensus for the drug of first choice was agreed as meropenem. Amoxycillin-clavulanate +clindamycin was the consensus choice for CAskin and soft tissue infection (SSIS) and piperacillin-tazobactam + metronidazole ±vancomycin for HA-SSIS. Ceftriaxone-tazobactam or piperacillin-tazobactam + gentamicin was consensus for CA-blood stream infections (BSI) with first choice+regimen for HA-BSI being meropenem/piperacillin-tazobactam +amikacin +fluconazole. For community-acquired urinary tract infection (UTI), first choice antibiotic was ciprofloxacin or ceftriaxone with a catheter-associated UTI (CAUTI) regimen of first choice being meropenem + fluconazole. CONCLUSION: Data from a multicenter three ICU surveillance and antibiograms and publications from different hospitals in the country was used to produce this evidence-based Nigerian-specific antimicrobial treatment guidelines of critically ill patients in ICUs by a group of experts from different specialties in Nigeria. The implementation of this guideline will facilitate learning, continuous improvement of stewardship activities and provide a baseline for updating of guidelines to reflect evolving antibiotic needs.

CONTEXTE: Il est bien établi que l'utilisation inappropriée des antimicrobiens est le principal moteur de la résistance aux antimicrobiens. Pour lutter contre ce phénomène, il a été démontré que la bonne gestion des antibiotiques permettait de réduire l'utilisation des antibiotiques, de diminuer la prévalence de la résistance, de réaliser des gains économiques significatifs et d'améliorer les résultats pour les patients. Au Nigéria, les directives antimicrobiennes pour les patients gravement malades dans les unités de soins intensifs (USI), souffrant d'infections, sont rares. Nous avons entrepris d'élaborer des lignes directrices sur les antimicrobiens pour cette catégorie de patients. MÉTHODES UTILISÉES: Un comité de 12 experts, composé de microbiologistes cliniques, d'intensivistes, de médecins spécialistes des maladies infectieuses, de chirurgiens et d'anesthésistes, a collaboré à l'élaboration de lignes directrices pour la prise en charge des infections chez les patients gravement malades dans les unités de soins intensifs nigérianes. Les lignes directrices sont basées sur des données publiées et des antibiogrammes prospectifs locaux provenant de trois unités de soins intensifs de Lagos, au Nigeria. Le comité a pris en compte la disponibilité des médicaments antimicrobiens appropriés dans les formulaires des hôpitaux. Les recommandations proposées ont été approuvées par consensus entre les membres du comité. RÉSULTATS: Candida albicans et Pseudomonas aeruginosa étaient les microorganismes les plus fréquemment isolés dans les trois unités de soins intensifs, suivis par Klebsiella pneumoniae, Acinetobacter baumannii et Escherichia coli. La thérapie ciblée est reconnue comme la meilleure approche pour la prise en charge des patients. Sur la base de divers antibiogrammes et publications provenant de différents hôpitaux du pays, l'amikacine est recommandée comme l'antibiotique empirique le plus efficace contre les entérobactéries et A. baumannii, tandis que la colistine et la polymixine B se sont révélées très efficaces contre toutes les bactéries. L'amoxicilline-clavulanate ou la ceftriaxone ont été recommandées comme médicaments de premier choix pour les pneumonies communautaires, tandis que la pipéracilline-tazobactam + amikacine ont été recommandées comme médicaments de premier choix pour le traitement des pneumonies associées aux soins. Pour les pneumonies acquises sous ventilation mécanique (PAV), le consensus sur le médicament de premier choix est le méropénem. L'amoxycilline-clavulanate +clindamycine était le choix consensuel pour les infections de la peau et des tissus mous et la pipéracilline-tazobactam + métronidazole ±vancomycine pour les infections de la peau et des tissus mous. HA-SSIS. Ceftriaxone-tazobactam ou pipéracilline-tazobactam + gentamicine a fait l'objet d'un consensus pour les infections de la circulation sanguine de l'AC (BSI), le premier choix de régime pour les HA-BSI étant le méropénem/pipéracilline-tazobactam +amikacine +fluconazole. Pour les infections urinaires communautaires, l'antibiotique de premier choix était la ciprofloxacine ou la ceftriaxone, le régime de premier choix pour les infections urinaires associées à un cathéter étant le meropenem +fluconazole. CONCLUSION: Les données issues d'une surveillance multicentrique de trois unités de soins intensifs, d'antibiogrammes et de publications de différents hôpitaux du pays ont été utilisées par un groupe d'experts de différentes spécialités nigérianes pour élaborer ces lignes directrices sur le traitement antimicrobien des patients gravement malades dans les unités de soins intensifs, fondées sur des données probantes et spécifiques au Nigeria. La mise en œuvre de ces lignes directrices facilitera l'apprentissage, l'amélioration continue des activités de gestion et fournira une base de référence pour la mise à jour des lignes directrices afin de refléter l'évolution des besoins en antibiotiques. Mots clés: Antimicrobiens, Résistance aux antimicrobiens, Gestion des antibiotiques, Lignes directrices, Soins intensifs, Unité de soins intensifs, Infections associées aux soins de santé.

Antibiotic susceptibility profiles and detection of genes mediating extended-spectrum ß-lactamase (Esbl) production in escherichia coli isolates from National Hospital, Abuja.

Background: Extended-spectrum beta-lactamases (ESBL) are the most widespread of the new beta-lactamases and are a significant threat to patient care in the hospital and the community. Aim: The study assessed the prevalence, antibiotic susceptibility profile, and major ESBL encoding genes among Escherichia coli isolated from clinical specimens of patients in the National Hospital, Abuja (NHA). Materials and Methods: E. coli isolated from diverse clinical specimens obtained from clinically proven cases of infection managed at the NHA were included in the study. The antimicrobial susceptibility was performed by the Kirby-Bauer method and E-test was used to confirm the ESBL phenotype. Multiplex polymerase chain reaction (PCR) was used to detect the genes mediating ESBL production. Results: Meropenem, fosfomycin, and tigecycline demonstrated excellent activities against all isolates: of the 400 isolates, 392 (98%), 386 (96.5%), and 362 (90.5%) were susceptible, respectively. Similarly, 358 (89.5%) were susceptible to amikacin, 323 (80.3%) nitrofurantoin, 281 (70.3%) ceftazidime, and 279 (69.8%) cefotaxime. A total of 271 (67.8%), 219 (54.8%), and 208 (52.0%) were resistant to amoxicillin-clavulanate, ciprofloxacillin, and gentamicin, respectively. However, all the isolates were resistant to ampicillin. There was a significantly higher proportion of multidrug resistance among ESBL-producing isolates compared to non-ESBL-producing isolates (P = 0.0001). Of the 121 phenotypically detected ESBL isolates, 119 (98.3%) harbored genes mediating the production of Cefotaximase- Munich (CTX-M), Temoniera (TEM) or Sulfhydryl Variable (SHV) enzymes. Conclusion: The prevalence of ESBLs among E. coli was relatively high, at 30.2%. About 81% of all blood isolates were ESBL-producers. blaCTX-M is the predominant type of ESBL gene among E. coli. A high proportion of the ESBL-producing isolates expressed a combination of two or three genes together.

A point-prevalence survey of carbapenem-resistant Enterobacteriaceae in two different cities in Kuwait and Nigeria

Background: The family Enterobacteriaceae belongs to the order Enterobacterales, a large diverse group of Gramnegative, facultatively anaerobic bacteria that sometimes cause multidrug-resistant infections which treatment options are often challenging. They are the leading cause of nosocomial bloodstream infection (BSI) and urinary tract infections (UTI). The objective of the study was to carry out a point-prevalence survey of antimicrobial resistance and carbapenem-resistant Enterobacteriaceae (CRE) clinical isolates in two hospitals in Kuwait and Nigeria. Methodology: Clinically significant bacterial isolates of patients from Kuwait and Nigeria, identified by VITEK-2 and MALDI-TOF mass spectrometry analysis were studied. Susceptibility testing of selected antibiotics was performed using E-test and broth dilution methods. Genes encoding carbapenemase, ß-lactamases, and extended-spectrum ßlactamases (ESBLs) were detected by conventional PCR and sequencing, and whole genome sequencing (WGS) analyses. Results: Of 400 isolates from Kuwait and Nigeria, 188 (47.0%) and 218 (54.5%) were Escherichia coli and 124 (31.0%) and 116 (29.0%) Klebsiella pneumoniae, respectively. The prevalence of CRE was 14.0% in Kuwait and 8.0% in Nigeria. The resistance rates of CRE isolates against colistin and tigecycline in Kuwait were 6.6% versus 25.0%, and in Nigeria were 14.2% versus 14.2%, respectively. blaOXA-181 gene was the commonest in CRE isolates in Kuwait and blaNDM-7 in Nigeria. The commonest ESBL gene among the CRE isolates was blaCTX-M-15 in both countries. AmpC resistance genes were present in only Kuwait isolates and mediated by blaEBC, blaCIT and blaDHA. WGS analysis of 12 selected CRE isolates with carbapenem MICs>32µg/ml but no detectable genes from conventional PCR, revealed the presence of multidrug efflux pump genes such as major facilitator superfamily antibiotic efflux pump and resistance-nodulation-cell division antibiotic efflux pump groups. Conclusion: The prevalence of CRE was higher among isolates from Kuwait than Nigeria and the genes encoding resistance in CRE were different. The presence of efflux pump was a main mechanism of resistance in most of the Nigerian CRE isolates.

Emergence of nosocomial-acquired extensively drug-resistant and pandrug-resistant Enterobacterales in a teaching hospital in Kuwait

Contexte: L'émergence et la montée en puissance des infections causées par des isolats d'entérobactéries ultrarésistantes (XDR) et pandrug-résistantes (PDR) constituent un sérieux défi clinique et de santé publique. L'isolement de bactéries Gram-négatives PDR (GNB) en milieu clinique est très rare et plus rare est l'infection causée par XDR GNB. En dehors des options thérapeutiques restreintes, ces infections sont associées à une augmentation de la mortalité et de la morbidité. Des études urgentes pour réévaluer les options thérapeutiques existantes et la recherche de nouvelles molécules antibiotiques sont désespérément nécessaires. Les objectifs de cette étude étaient de signaler l'émergence d'infections à CRE multirésistantes (MDR), difficiles à menacer, rarement rencontrées dans notre hôpital et d'enquêter sur leur épidémiologie moléculaire. Méthodologie: Il s'agissait d'une analyse observationnelle rétrospective de six patients atteints d'infections graves causées par des isolats d'entérobactéries XDR et PDR à l'hôpital universitaire Mubarak AL Kabeer, Jabriya, Koweït, sur une période d'un an et demi. Les mécanismes de résistance de ces isolats ont ensuite été étudiés de manière prospective par caractérisation moléculaire et études génomiques. Résultats: La majorité des infections ont été causées par Klebsiella pneumoniae (83,3%, 5/6) et une (16,6%) a été causée par Escherichia coli. Trois patients avaient une infection du sang (BSI), un avait à la fois une BSI et une infection des voies urinaires (UTI), un avait une infection des voies respiratoires et le dernier avait une UTI. Deux patients ont été infectés par des producteurs d'OXA-48, un patient a été infecté par un producteur de NDM-1, un patient a été infecté par un producteur de NDM-5, un patient a été infecté par un producteur de NDM-1 et d'OXA-48 et le dernier patient a été infecté avec le producteur NDM-5 et OXA-181. Pour un traitement définitif, tous les patients ont reçu une thérapie combinée. Le taux de mortalité était élevé (50.0%). Conclusion: Le taux de mortalité élevé associé aux infections XDR et PDR Enterobacterales et les options antimicrobiennes limitées pour le traitement soulignent la nécessité d'améliorer la détection de ces infections, l'identification de mesures préventives efficaces et le développement de nouveaux agents avec une efficacité clinique fiable contre elles.

Prevalence of target anaerobes associated with chronic periodontitis.

INTRODUCTION: Periodontal diseases are a group of chronic infections that destroy tissues surrounding and supporting the teeth. Data on the anaerobes associated with periodontal infections in Kuwait is lacking. AIM: To investigate the target anaerobes associated with chronic periodontitis (CP) in patients admitted to Dental Clinics in Kuwait University Health Sciences Center, Kuwait. METHODOLOGY: Patients with CP (severe and moderate) were recruited into this study during a period of 15 months. Samples were collected directly from inside the gingival pockets and subjected to semi-quantitative PCR assays. RESULTS: A total of 30 patients, stratified into moderate and severe CP and 31 healthy individuals, used as controls, were studied. Nine (30 %) of the 30 patients were in the 50-59-year age group. The detection rate of Aggregatibacter actinomycetemcomitans between the patients (9 : 30 %) versus the controls (5 : 16.1 %) was non-significant (P >0.05). Fusobacterium spp., were detected in all patients versus 29 (93.1 %) controls, (P >0.05). However, four target anaerobes were significantly associated with CP patients; Porphyromonas gingivalis was detected in ten (33.3 %) patients versus two (6.4 %) controls (P <0.0001); Tannerella forsythia 25 (83.3 %) versus 16 (51.6 %) controls (P <0.0001); Parvimonas micra 27 (90 %) versus 16 (51.6 %) controls (P <0.0001) and Treponema denticola, 18 (60 %) versus nine (29 %) controls (P <0.0001), respectively. Prevotella spp. were detected in 27 (90 %) patients and 30 (96.7 %) controls (P>0.5). There was no significant difference in the burden of Prevotella spp. between patients and controls determined by semi-quantitative PCR assays. CONCLUSION: Some (4/7) of the target anaerobes were significantly associated with CP in our study. P. gingivalis was the most strongly associated anaerobe with CP, although not the keystone bacteria, while Prevotella spp. was similar to the healthy controls.

Antimicrobial susceptibility profiles of anaerobic bacteria, isolated from human clinical specimens, within different European and surrounding countries. A joint ESGAI study.

OBJECTIVES: Studies on the antimicrobial susceptibility profile of anaerobic bacteria are underrepresented in the literature. Within this study we aim to give an extensive overview of the differences in antimicrobial susceptibility profiles between different European and surrounding countries. METHODS: Minimal inhibitory concentration (MIC) data of different antibiotics were collected from 10 participating laboratories, representing an equal number of countries. All MIC's were determined using Etest, according to the protocol used by the participating laboratory. Anaerobic genera represented by at least 10 clinical isolates were included in the study. RESULTS: Each country tested different antibiotics, sometimes depending on the kind of infection and/or the anaerobic species isolated. All countries tested clindamycin and metronidazole. Resistance rates differed remarkably between the different countries. Especially in Kuwait, resistance was high for all tested antibiotics. Unexpected metronidazole resistance was observed for Finegoldia magna isolates, Peptoniphilus isolates and Eggerthella lenta isolates. CONCLUSIONS: Due to the extensive differences in antimicrobial susceptibility profile of anaerobic bacteria isolated within different countries, we strongly recommend to perform this kind of study on a regular basis.

Comparative evaluation of two matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) systems for the identification of clinically significant yeasts.

OBJECTIVES: To prospectively evaluate the performance of two matrix-assisted laser desorption/ionization time-of-flight mass spectrometry systems (MALDI-TOF MS) for the identification of clinically significant yeast isolates compared to the VITEK 2 system. METHODS: One hundred and eighty-eight consecutive yeast isolates were analyzed by Bruker Biotyper and VITEK MS. The results were compared with the conventional VITEK 2 yeast identification system. Discrepant results were resolved by direct sequencing of rDNA. RESULTS: Accurate identification by VITEK 2, VITEK MS, and Bruker Biotyper MS was 94.1% (177/188), 93.0% (175/188), and 92.6% (174/188), respectively. Three isolates were not identified by VITEK MS, while nine Candida orthopsilosis were misidentified as Candida parapsilosis, as this species is not present in its database. Eleven isolates were not identified or were wrongly identified by Bruker Biotyper and although another 14 were correctly identified, the score was unreliable at <1.7. CONCLUSION: The overall accuracy of rapid MALDI-TOF MS systems was essentially comparable to that of the conventional VITEK 2 yeast identification system. However, future expansion of the databases may further improve the outcome and accuracy of identification of yeast species.

Three distinct clones of carbapenem-resistant Acinetobacter baumannii with high diversity of carbapenemases isolated from patients in two hospitals in Kuwait.

OBJECTIVES: This study was undertaken to investigate the clonal relatedness of multidrug-resistant (MDR) Acinetobacter baumannii isolates collected from patients in two teaching hospitals in Kuwait. MATERIALS AND METHODS: Clinically significant consecutive isolates of A. baumannii obtained from patients in the Mubarak (36) and Adan (58) hospitals over a period of 6 months were studied. These isolates were identified using molecular methods, and their antimicrobial susceptibility was determined by the Etest method. The mechanism of resistance to carbapenem was investigated by PCR, and pulsed-field gel electrophoresis (PFGE) was used to determine the clonal relatedness of MDR isolates. RESULTS: Of the 94 isolates investigated, 80 (85.1%) were multidrug resistant (MDR). The A. baumannii PFGE clone A and subclone A1 were the most prevalent in patients infected with MDR isolates. Fifty-five (94.8%) and 15 (41.7%) of the MDR isolates from the Adan and Mubarak hospitals, respectively, belonged to PFGE clone A; isolates in this group showed higher resistance rates to antibiotics than isolates form other groups. Of the 94 isolates, 40 (42.6%) were resistant to either imipenem or meropenem or to both (CRAB). Most CRAB isolates (29/40 or 72.5%) carried bla genes, which code for MBL (VIM-2 and IMP-1) enzymes. Two isolates harbored bla(OXA-23). CONCLUSION: Three distinct clones of CRAB were isolated, providing evidence of a high diversity of carbapenemases among our geographically related isolates.

The prevalence of Chlamydia trachomatis and Neisseria gonorrhoeae infections among men with urethritis in Kuwait.

PURPOSE: Chlamydial non-gonococcal urethritis and gonorrhoea are the most common sexually transmitted bacterial infections worldwide. Data on these infections are scanty in the Islamic world, especially Kuwait. The objective of this study was to establish the prevalence of Chlamydia trachomatis and Neisseria gonorrhoeae among men with symptomatic urethritis in Kuwait. METHODS: Men with urethral discharge seen and managed at eight governmental hospitals were recruited into the study. A pair of urethral swab and first-voided urine sample were taken from the patients and sent immediately to the laboratory where they were processed using strand displacement nucleic acid amplification kits (SDA; ProbeTec, Becton Dickinson); one pair per patient was studied. RESULTS: A total of 426 symptomatic men were studied, out of whom 155 (36.4%) were infected by either C. trachomatis or N. gonorrhoeae, or both. The overall prevalence rates of C. trachomatis and N. gonorrhoeae were 12.4% and 23.9%, respectively. There was no significant difference in chlamydial and gonococcal prevalence between Kuwaiti men and non-Kuwaitis (P>0.05). Infection rates were much lower in married men than unmarried men. Men in the age range of 21-35 years were more vulnerable to both infections. CONCLUSION: The findings show that N. gonorrhoeae and, to a lesser extent, C. trachomatis are common in men with urethritis in Kuwait. Appropriate preventive strategies that conform to Islamic rules and values should be of highest priority of the policymakers.

An outbreak of CTX-M-15-producing Klebsiella pneumoniae isolates in an intensive care unit of a teaching hospital in Kuwait.

OBJECTIVE: This study reports an outbreak of Klebsiella pneumoniae infections in 14 patients during a 2-month period (August-September, 2008) in the intensive care unit (ICU) of a teaching hospital in Kuwait. MATERIALS AND METHODS: The clinical sources were blood (9), urine (3) and respiratory secretions (2) identified by the automated VITEK-2 ID System. Susceptibility testing was performed by the E-test method. Extended-spectrum ß-lactamase (ESBL) production was assessed using the ESBL E-test and confirmed by PCR. Carriage of bla genes was determined by PCR and sequence analysis. The transferability of resistance phenotypes was demonstrated by conjugation experiments and clonal relatedness was determined by PFGE. RESULTS: The isolates were susceptible to imipenem, meropenem, and tigecycline and produced ESBL. All isolates yielded an amplicon of 499 bp with universal consensus primers (MA primers). DNA sequence analysis showed that they all harboured bla CTX-M-15 and bla TEM-1 genes. The environmental isolate obtained from a suction machine was also CTX-M-15/TEM-1 producer. The resistance phenotypes were transferrable to the Escherichia coli J53 r strain. PFGE, revealed two clones, A and B, related with a Dice coefficient of >94.1%. A mortality rate of 21.4% was recorded. CONCLUSION: The outbreak was contained by robust and aggressive infection control measures. This study highlights the first outbreak of CTX-M-15-producing K. pneumoniae associated with high mortality in an adult medical ICU in Kuwait.

Emergence of tigecycline and colistin resistance in Acinetobacter species isolated from patients in Kuwait hospitals.

The development of resistance is a compelling reason for reviewing administration of antibiotics. Recently, most Acinetobacter infections are caused by multidrug-resistant (MDR) strains which have necessitated the use of tigecycline or colistin. This study was undertaken to determine the susceptibility of Acinetobacter spp. to these and other drugs. A total of 250 Acinetobacter isolates were collected from the 8 government hospitals over a period of 6 months. Susceptibility to 18 antibiotics, including tigecycline and colistin, was investigated by determining their minimum inhibitory concentrations using E test. Of the 250 isolates, 13.6% and 12% were resistant to tigecycline and colistin. A total of 25.2% and 37.2% were resistant to imipenem and meropenem, respectively. Of the 250 isolates 88.4% were MDR. This relatively high prevalence of tigecycline and colistin-resistant isolates indicates an emerging therapeutic problem which may severely compromise the treatment of MDR Acinetobacter spp. infections in Kuwait.

A 4-year prospective study of septicemia in pediatric surgical patients at a tertiary care teaching hospital in Kuwait.

BACKGROUND: Critically ill children are at high risk for developing nosocomial infections that contributes to death in 4% of all pediatric intensive care unit admissions. This prospective study was undertaken to determine the prevalence of septicemia in the pediatric surgery department of a large tertiary care teaching hospital in Kuwait and to evaluate the risk factors, the microbial etiology, and the antimicrobial susceptibility pattern of the isolated microorganisms. METHODS: All patients admitted to the pediatric surgery department from January 2001 until December 2004 with the diagnosis of septicemia were included in the study, and the microbiologically proven cases were then analyzed. The patients' demographics and risk factors for sepsis were recorded. All positive blood cultures were subjected to identification and antimicrobial susceptibility testing by VITEK 2(bioMerieux, Marcy l'Etoile, France). RESULTS: Of 3408 patients suspected to have septicemia, 78 (2.3%) patients developed microbiologically documented septicemias, 26% of those were low-birth weight patients, and 82% were patients with congenital anomalies; 87% of those needed surgical intervention. More than 50% were admitted to the intensive care unit, and 80.5% needed ventilatory support. Fifty-seven percent had early onset septicemia. Gram-positive and gram-negative bacteria accounted for 54% and 39% of the septicemia cases, respectively, whereas Candida spp was responsible for 7%. More than 50% of the staphylococci were resistant to cloxacillin, and all gram-positives were uniformly susceptible to glycopeptides and linezolid. Gram-negative bacteria showed variable resistance to cephalosporins (65%), piperacillin/tazobactam (29%), and carbapenems (11%). The attributable mortality rate for these septic episodes was 19% mainly because of gram-negative bacteria and Candida. CONCLUSION: The main etiologic agents of neonatal septicemia were coagulase-negative Staphylococcus, Pseudomonas aeruginosa, and members of the family Enterobacteriaceae. Empirical therapy with piperacillin/tazobactam or carbapenems for gram-negative septicemia and glycopeptides for gram-positive septicemia was effective.

Sequence analysis of bla(CTX-M) genes carried by clinically significant Escherichia coli isolates in Kuwait hospitals.

OBJECTIVE: To investigate the extent, distribution and sequence analysis of bla(CTX-M) genes carried by Escherichia coli isolated from patients admitted to all government hospitals in Kuwait. METHODS: Extended-spectrum ß-lactamase (ESBL)-producing E. coli isolates were collected from the 8 major hospitals in Kuwait. CTX-M ESBLs were analyzed by PCR and sequenced. Clonality of the positive isolates was determined for genetic relatedness using pulsed-field gel electrophoresis (PFGE) with XbaI digestion of the genomic DNA. RESULTS: Of the 136 ESBL-positive isolates, 106 (77.9%) harbored bla(CTX-M) genes. Among these, bla(CTX-M-15) was the most frequent with a prevalence rate of 84.1%, followed by bla(CTX-M-14) (6.8%), bla(CTX-M-14b) (5.7%) and bla(TOHO-1) (3.4%). Ninety-three (87.7%) were isolated from Kuwaiti (35.9%), Egyptian (31.1%) and Indian (20.8%) nationals; the majority of isolates positive for bla(CTX-M-15) were mainly from these 3 nationalities. PFGE analysis did not demonstrate any clustering of positive isolates in any particular hospital. CONCLUSION: This study confirms an explosive emergence of CTX-M-15 ß-lactamase among E. coli isolates in Kuwait and shows that the strains were clonally heterogeneous with no evidence of inter- or intra-hospital spread. Thus Kuwait may represent an important source of CTX-M-15-positive E. coli.

Analysis of prevalence, risk factors and molecular epidemiology of Clostridium difficile infection in Kuwait over a 3-year period.

We conducted a prospective study to evaluate the prevalence and epidemiology of CDI in Kuwait government hospitals over a 3-year period, January 2003 to December 2005, to determine the ribotypes responsible for CDI and to estimate the prevalence of ribotype 027. We also conducted a case-control study to identify the risk factors in our patient population. A total of 697 stool samples from patients with suspected CDI were obtained and sent to Anaerobe Reference Laboratory, Faculty of Medicine, Kuwait University for Clostridium difficile toxin detection, culture and PCR ribotyping. During the period, 73 (10.5%) out of 697 patients met the case definition of CDI. Of these, 56 (76.7%) were hospital-acquired and 17 (23.3%) were from outpatient clinics. Thus, the prevalence of hospital-acquired CDI amongst patients with diarrhoea was 8% over the study period; the prevalence in 2003, 2004 and 2005 was 9.7%, 7.8% and 7.2%, respectively. Our data showed that 42.9% of the CDI patients were above 60 years, of which >79% were aged 71 years and above. Patients with CDI were more likely than the controls to have been exposed to immunosuppressive drugs and feeding via nasogastric tube. The most common ribotypes isolated during this study were 002, 001, 126 and 140 and they represent 55.1% of all isolates. PCR ribotype 027 was not isolated.

Comparative in vitro activity of tigecycline and other antimicrobial agents against Shigella species from Kuwait and the United Arab of Emirates.

Shigella species isolated from stool samples of symptomatic patients of all age groups at the Mubarak Al Kabir Hospital and Infectious Diseases Hospital, Kuwait and Tawam Hospital, UAE during a 2-year period were investigated for their susceptibility to tigecycline and several other antibiotics by determining the minimum inhibitory concentrations (MICs) using the E test method. A total of 100 and 42 strains were collected from UAE and Kuwait, respectively. The extent of drug resistance in the Shigella spp. isolates from these two countries was analyzed by criteria recommended by the Clinical and Laboratory Standards Institute (CLSI). Amikacin, cefotaxime, cefuroxime, ciprofloxacin, imipenem, meropenem, piperacillin-tazobactam and tigecycline had excellent activities against all isolates from UAE and Kuwait with MIC(90s) of 12, 0.094, 4, 0.012, 0.25, 0.032, 3 and 0.25 microg/ml and 4, 1, 4, 0.125, 0.38, 0.19, 3 and 0.25 microg/ml, respectively. Half of all isolates from both countries were resistant to ampicillin. None of the isolates in Kuwait was resistant to amoxicillin-clavulanic acid compared with 22% in UAE. Resistance to chloramphenicol was recorded in 50 and 36% of the isolates in Kuwait and UAE, respectively. The percentages of non-susceptibility to trimethoprim-sulfamethoxazole and tetracycline were very high in Kuwait and UAE (76% vs. 92% and 76% vs. 98%, respectively). Notably, one isolate, S. flexneri, from UAE had reduced susceptibility to ciprofloxacin (MIC, 0.25 microg/ml). Four (2.8%) of the isolates were ESBL producers by the E test ESBL method but could not be confirmed by PCR using primers for bla(CTX-M), bla(SHV) and bla(TEM). In conclusion, Shigella spp. isolated from symptomatic patients in Kuwait and the UAE demonstrated high rates of resistance to the first-line antibiotics but very susceptible to the carbapenems, cephalosporins, fluoroquinolones and tigecycline. Tigecycline holds promise as a potential drug of choice for the therapy of severe shigellosis.

National surveillance of antimicrobial susceptibility of CTX-M-positive and -negative clinical isolates of Escherichia coli from Kuwait government hospitals.

Antibiotic resistance in Escherichia coli is becoming a complex therapeutic problem. Surveillance programs are valuable tools and offer important information on bacterial resistance trends. This study was undertaken to determine the susceptibility of clinically significant isolates of E. coli obtained from patients admitted to 8 Kuwait government hospitals and to examine how this was influenced by the production of CTX-M extended-spectrum beta-lactamases (ESBLs). The susceptibility of 876 consecutive clinically significant strains of E. coli to 13 antibiotics was determined by Etest. ESBL production was assessed by ESBL-Etest method and the presence of CTX-M beta-lactamases was confirmed by PCR technique. Of the 876 isolates, 604 (69%) were highly non-susceptible to ampicillin with MIC(90 )of >256 microg/ml. Resistance to the 3(rd)-generation cephalosporins ranged from 7.5% in the Maternity hospital to 29% in the Ibn Sina hospital; ciprofloxacin resistance rates ranged from 14% and 40%, respectively. Carbapenems and amikacin demonstrated excellent activity. The minimum inhibitory concentrations (MIC(90)) of cefotaxime, ceftazidime, cefepime and ciprofloxacin were >256, 64, >256 and >32 microg/ml, respectively for CTX-M-positive isolates versus 0.5, 1, 025 and 0.125 microg/ml for CTX-M-negative strains. Frequencies of CTX-M-positive isolates within the cefotaxime MIC ranges of 1-2, 3-8, 9-16 and >16 microg/ml were 0, 4, 15 and 81%, respectively. In conclusion, the susceptibility of E. coli to the 3(rd )generation cephalosporins and ciprofloxacin was influenced by the presence of CTX-M ESBL and a high proportion of the CTX-M-producing isolates were in the susceptibility ranges of cefotaxime.

A case of community-onset meningitis caused by hospital methicillin-resistant Staphylococcus aureus successfully treated with linezolid and rifampicin.

OBJECTIVE: To report a relatively rare presentation of methicillin-resistant Staphylococcus aureus (MRSA) meningitis in a previously healthy boy in Kuwait. CLINICAL PRESENTATION AND INTERVENTION: A 14-year-old boy presented with a 2 weeks' history of headache and fever with increasing severity. He developed photophobia and double vision 2 days prior to his hospital visit and received ceftriaxone for 6 days prior to admission to the hospital. There was no history of head trauma or neurosurgical operation. Lumbar puncture revealed a slightly turbid cerebrospinal fluid with pleocytosis and greatly reduced glucose, elevated protein level and on culture grew MRSA. Staphylococcal chromosome cassette mec (SCCmec) typing revealed that it belonged to SCCmec type III and sequence type 238 (ST238-SCCmec-III). Polymerase chain reaction screening for the presence of Panton-Valentine leukocidin (PVL) genes yielded a negative result; all these findings were consistent with hospital-acquired MRSA. He was treated with intravenous linezolid and rifampicin for 2 weeks, made good response and was discharged home fully recovered and well. CONCLUSION: Hospital MRSA should be considered in the differential diagnosis of the causative agents of community-onset meningitis in healthy patients even without predisposing factor.

Surveillance and trends of antimicrobial resistance among clinical isolates of anaerobes in Kuwait hospitals from 2002 to 2007.

The susceptibility trends for all anaerobes processed by the Anaerobe Reference Laboratory against various antibiotics were determined by using data for 2557 isolates referred by all government hospitals in Kuwait from 2002 to 2007. MIC were determined for the following anti-anaerobic antibiotics: amoxicillin-clavulanic acid, clindamycin, imipenem, meropenem, metronidazole, penicillin, piperacillin, piperacillin-tazobactam and vancomycin (for Gram-positive anaerobes only), using E-test method. The commonest isolates were Bacteroides fragilis (36.8%), followed by Peptostreptococcus spp. (21.9%), Bacteroides ovatus (15.5%) and Prevotella bivia (12.1%). In addition, Prevotella oralis and other Bacteroides spp. represented 8.5% and 8.1% of total number of isolates, respectively. Resistance rate varied among the antimicrobial agents and the species tested. The beta-lactams, with the exception of penicillin, were the most active drugs. Piperacillin-tazobactam was the only antimicrobial agent to which all the isolates were uniformly susceptible. Imipenem and metronidazole were highly active with resistance rate of only <5% recorded against most isolates. However, 42.8, 55.8 and 9.3% of Clostridium difficile isolates were resistant to imipenem, clindamycin and meropenem, respectively. It is noteworthy that from 2002 to 2007, there was a gradual increase in resistance rates to clindamycin, amoxicillin-clavulanic acid and piperacillin among B. fragilis. Periodic surveillance of antibiotic resistance among the anaerobic bacteria is recommended as a guide to empiric antibiotic use and formulation of guideline for appropriate choice of antimicrobial therapy in anaerobic infections.

Correlation of multidrug resistance, toxinotypes and PCR ribotypes in Clostridium difficile isolates from Kuwait.

Clostridium difficile is a common cause of nosocomial diarrhea. its role in community-acquired diarrhea is also becoming an important public health concern. Hardly any studies have correlated strain ribotypes, toxinotypes and multidrug resistant (MDR) profiles. To investigate these characteristics, 65 C. difficile isolates obtained from stool samples of patients whose cultures were negative on admission but became positive after 48 h of admission to the ICUs of our hospitals were studied to determine the prevalent ribotypes, toxinotypes and their relationship with the MDR profiles using ELISA/cytotoxicity assays, PCR and Etest methods. The toxin-producing strains were toxinotyped by the PCR-RFLP technique. Of the 65 isolates, 42 (64.6%) were toxigenic (T). The isolates were of diverse ribotypes but types 097, 078, 056 and 039 (NT) were predominant. thirty (71.4%) of 42 T and 13 (56.5%) of 23 NT strains were multiresistant to 3 or more antibiotics. Only 3 toxinotypes (0, "V-like" and XII) were encountered. Of the 42 t strains, 30 (71.4%) were of toxinotype 0, and 12 belonged to variant toxinotypes: 4 (9.4%) to toxinotype XII and 8 (19%) to "V-like" toxinotype in which amplified B1 PCR fragments was amplified as expected for toxinotype V but the A3 PCR fragment could not be amplified. The 43 mDR strains were assigned to 3 arbitrary resistance groups; groups 1, 11 and III. the most prevalent isolates (37; 86.1%) were in group II. Of the predominant T ribotypes (097, 078 and 056), c. 62% clustered in group II. Although the number of strains toxinotyped was small, ribotyping and toxinotyping correlated well with the published literature, except for 078 with a novel "V-like" toxinotype. Antibiogram was not as clear-cut.