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.

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.

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.

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.

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.

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.

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.

Surveillance of antibacterial resistance in Staphylococcus aureus isolated in Kuwaiti hospitals.

OBJECTIVE: To investigate the prevalence of antibiotic resistance among Staphylococcus aureus isolated in Kuwaiti hospitals. MATERIALS AND METHODS: S. aureus were isolated and identified following standard microbiological methods. Antibacterial susceptibility test was performed by disk diffusion and the measurement of minimum inhibitory concentration with E-test strips. RESULTS: A total of 1,846 S. aureus isolates were analyzed from 13 hospitals between 1 March and 30 October 2005. They were isolated from 1,765 (95.6%) inpatients and 81 (4.4%) outpatients. Methicillin resistance was detected in 588 (32.0%) of the isolates. The methicillin-resistant S. aureus (MRSA) consisted of 461 (78%) multiresistant and 127 (22%) nonmultiresistant isolates. The nonmultiresistant MRSA consisted of epidemic MRSA-15 and community-associated MRSA. The community-associated MRSA was detected in all hospitals with MRSA, indicating its establishment in Kuwaiti hospitals. The proportion of isolates resistant to gentamicin, kanamycin, erythromycin, tetracycline, ciprofloxacin, fusidic acid and trimethoprim was higher among MRSA than methicillin-susceptible S. aureus (MSSA) isolates. Twenty-four and 22% of MRSA and MSSA isolates, respectively, expressed reduced susceptibility to vancomycin (minimum inhibitory concentration = 3-4 mg/l). CONCLUSION: The study revealed the presence of methicillin resistance in 32% of S. aureus isolated in Kuwaiti hospitals and revealed an increase in the number of MRSA and MSSA with reduced susceptibility to vancomycin.

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.

In vitro activity of linezolid and other antibiotics against Gram-positive bacteria from the major teaching hospitals in Kuwait.

Multidrug-resistant Gram-positive bacteria are an increasingly pressing problem in the clinic. Consequently, linezolid, a recently introduced oxazolidinone with Gram-positive activity, was tested in comparison with 10 other antibiotics against 8103 clinically significant Gram-positive cocci by Etest, disk diffusion and Vitek methods. Linezolid demonstrated excellent activities against all isolates. Vancomycin and teicoplanin demonstrated equally excellent activity against almost all isolates. The methicillin-resistant Staphylococcus aureus (MRSA) strains were all susceptible to the glycopeptides and linezolid, but resistant to erythromycin (96%), fusidic acid (91.5%), gentamicin (84%) and clindamycin (73%). Forty one and 39% of the Streptococcus pneumoniae isolates were resistant to penicillin (MIC >0.5 microg/ml) and erythromycin (MIC >1 microg/ml), respectively. S. agalactiae susceptibility was 9% and 10% resistant to clindamycin and erythromycin, respectively. In conclusion, all the Gram-positive isolates tested were susceptible to linezolid. With its oral bioavailability profiles, it obviously holds great promise. Our data should be a useful addition to the literature from the Middle East.

High frequency of isolation of antibiotic-resistant oral Viridans streptococci from children in Kuwait.

Antimicrobial resistance among the Viridans group of streptococci (VGS) has emerged as a hindrance to effective antibiotic therapy. Our objective was to evaluate the prevalence of antibiotic-resistant VGS in healthy children. Plaque samples were collected from tooth and tongue surfaces of 102 healthy subjects. Serially diluted samples were inoculated onto BHI agar plates and Mitis Salivarius Agar (MSA) plates and incubated as appropriate. Representative colonies were identified to species level by standard methods. Susceptibility of the VGS was performed by determining the minimum inhibitory concentrations (MICs) of 11 antibiotics using Etest. Of the 540 VGS isolates from both sites, 58% were from the tooth surfaces and 42% from the tongue. The most prevalent were S. salivarius (21.5%) and S. sanguis (16.3%). Imipenem and vancomycin had excellent activities. Resistance rates to trimethoprim, amoxicillin, piperacillin, erythromycin, cefuroxime and cephalothin, were 60.7, 40.8, 34.7, 32.6, 27.5 and 25.3%, respectively. Resistance rates to penicillin and clindamycin were 15.9% and 15.4%, respectively. The majority of the erythromycin-resistant isolates were from the tongue; 41% versus 29%. At the species level, 26% and 23% of S. salivarius and 23% and 14% of S. mutans from the tooth and tongue, respectively were resistant to penicillin. The data show species-related and site-related variations in the susceptibility pattern and an emerging high prevalence of antibiotic-resistant VGS. The difference in the susceptibilities between the species underscores the importance of accurate-identification and the need for surveillance of antimicrobial resistance among clinical isolates in our hospitals.

The bacteriology of infected malignant ulcers.

Infected ulcerated malignant tumours are often foul smelling and covered with necrotic tissue. We have studied 70 patients with infected ulcers; 30 of the underlying lesions in these patients were carcinoma of the breast, and 19 were a variety of skin cancers. Anaerobes were the predominant organisms isolated from individual ulcers. Of the 179 anaerobes isolated, 37 were Bacteroides asaccharolyticus, 31 each were B melaninogenicus and anaerobic streptococci, 29 B fragilis, and 17 B ureolyticus. Among the facultative organisms Escherichia coli was the commonest and was isolated mainly from patients with carcinoma of the breast. Most infections were mixed, yielding both anaerobes and aerobes and this made interpretation of the role of individual pathogens difficult to assess.

Bacteraemia due to a rifampicin-resistant strain of Bacteroides fragilis.

A strain of Bacteroides fragilis with high-level chromosomal resistance to rifampicin was isolated by blood culture from a patient with bacteraemia after gastrointestinal surgery. He had been receiving antituberculous therapy with rifampicin for nine months. This resistance led to some difficulty in the recognition and identification of the isolate by methods that depended upon antibiotic sensitivity patterns.

Increased serum levels of interferon-gamma and interleukin-12 during human brucellosis.

Brucellosis is a zoonotic disease that often becomes chronic with a high rate of recurrence. To understand the cytokines induced during this infection we determined the levels of interleukin (IL)-1beta, IL-2, IL-4, IL-8, IL-12, tumor necrosis factor-of (TNF-alpha) and interferon-gamma (IFN-gamma) in serum of patients with brucellosis and compared with those without brucellosis and controls. Control sera were taken from healthy persons residing in an area that was not endemic for brucellosis. The levels of IL-1, IL-2, IL-4, and TNF-alpha were not detectable in all the sera from patients. There was no difference in the level of IL-8 in patients with brucellosis and those without this disease. However, IL-8 was significantly higher in these two groups of patients compared with the controls. Significantly higher levels of IL-12 and IFN-alpha were found in the serum of patients with brucellosis compared with patients without brucellosis and controls. These data indicate that there is induction of Thl type cytokines during human brucellosis.

The prevalence and antibiotic susceptibility pattern of gram-negative bacterial isolates in two ICUs in Saudi Arabia and Kuwait.

In surveys of the prevalence and antibiotic susceptibility pattern of consecutive Gram-negative bacterial isolates in two intensive care units (ICUs) in Saudi Arabia (Jeddah) and Kuwait, 106 and 101 isolates, respectively, were analyzed. The most common bacterial isolates in Jeddah versus Kuwait ICUs were Pseudomonas aeruginosa (26%, 26%), Escherichia coli (23%, 3%), Klebsiella pneumoniae (20%, 17%), inducible Enterobacteraecae group (17%, 14%), and Acinetobacter spp. (9%, 33%). Overall, about 99% of all isolates were susceptible to ciprofloxacin in both centers, whereas 87 and 96% were susceptible to imipenem, 69 and 64% to ceftazidime, 59 and 52% to cefotaxime, and 25 and 67% to piperacillin, respectively, in Jeddah and Kuwait. Prior antibiotic usage was more common among patients in Jeddah than in Kuwait. Dominant features of the study in Jeddah were the E. coli and Klebsiella spp. demonstrating multiresistance to monobactams, cephems, and all three aminoglycosides, and evidence of two classes of resistance to beta-lactam antibiotics which were not seen among the Kuwaiti isolates. The Kuwaiti Pseudomonas spp. were more sensitive to imipenem than the Jeddah Pseudomonas spp. (100% versus 68%). The higher number of resistant bacteria seen in Jeddah than Kuwaiti may be a reflection of the higher antibiotic consumption, in particular higher usage of broad spectrum cephalosporins in Jeddah ICU.

The bactericidal action of human serum on Bacteroides species.

Sera obtained from 60 healthy normal subjects were tested for their inhibitory action against four clinical isolates of the Bacteroides fragilis group. All the sera inhibited clinical strains of B. vulgatus and B. ovatus, 92% of 60 sera inhibited B. thetaiotaomicron and 62% inhibited B. fragilis. Bacterial inhibition required components of uninactivated serum and was related to the serum concentrations and species of the bacteria. The viable counts of all the strains, except B. fragilis, were significantly reduced in pooled sera from patients with anaerobic systemic infections and from non-infected patients. The bactericidal activity of the sera from infected patients was more pronounced than that of the 'normal' sera, on all strains except B. fragilis. These observations may explain in part the predominance of B. fragilis in serious clinical infections involving anaerobes.

The effect of crude extracts of nine African chewing sticks on oral anaerobes.

Chewing sticks are widely used in Nigeria for dental and oral hygiene. In-vitro susceptibility tests were done with crude extracts from nine popular sticks on four species of Bacteroides. Serindeia warneckei chewing stick had the greatest and most consistent inhibitory effect on the four species; extracts from bark and pulp were bactericidal at concentrations of less than or equal to 1%. Extracts of other sticks, when inhibitory, were only so at higher concentrations--in the range 2-30%. All the black-pigmented oral anaerobes were very susceptible to eight of the nine chewing-stick extracts but non-pigmented anaerobes showed variable susceptibilities.

The development of the bacterial flora in normal neonates.

The development of the bacterial flora of neonates during the first week of life was studied in 23 babies. Specimens of meconium or faeces were collected and swabs taken from the umbilicus and mouth on days, 1, 2, 3 and 6. The bacteria present were isolated on a variety of plain and selective media. The predominant faecal organisms by the end of the first week were anaerobes. Bifidobacteria were isolated from all the neonates and bacteroides and clostridia were isolated from 78.3%. Bifidobacteria and bacteroides were present in large numbers; other species were isolated in smaller numbers. Enterococci were isolated from all neonates, enterobacteria from 82.6%, anaerobic cocci from 52.2%, and streptococci and staphylococci from 34.8% each. Staphylococcus aureus was the predominant species isolated from the umbilicus; it was isolated from 21.7% of neonates on the first day rising to 87.0% by the sixth day and represented 49% of isolates from this site. S. albus, streptococci, enterococci and Escherichia coli were each isolated from a few neonates. Viridans streptococci (31.4% of isolates) and Streptococcus salivarius (25.1%) were the commonest species recovered from the mouth. They were present from 8 h after birth; S. albus and Neisseria spp. were isolated later on the first day, and anaerobic species of Veillonella and Bifidobacterium appeared on the second day.

Transferable plasmid-mediated antibiotic resistance in Bacteroides.

Plasmid-mediated resistance to chloramphenicol (Chlr), erythromycin (Eryr), tetracycline (Tetr) and clindamycin (Clindr) was transferred from three clinical isolates of Bacteroides fragilis and one faecal isolate of B. thetaiotaomicron to strains of B. fragilis, B. distasonis and Escherichia coli, and subsequently to B. fragilis and E. coli second-and third-stage recipients in series. Successful transfer was achieved by membrane-filter and centrifugation techniques that provide stable cell-to-cell contact but not by simple mixed broth culture. Chlr Eryr Tetr and Clindr Eryr were transferred at high frequency (1.9 x 10(-3)-1.8 x 10(-4)) but Tetr was transferred at low frequencies (1-1.6 x 10(-6)). Segregation of resistance markers was observed with selection for Tetr when donors were Chlr Eryr Tetr and Chlr Tetr. All transcipients were identical with the parent recipient strains but had the resistance markers of the donor strains. Resistance to antibiotics other than tetracycline was cured by growth with subinhibitory concentrations of aminoacridines and ethidium bromide for 24 h; cure of solitary Tetr required longer incubation (21 days). Identical plasmid DNA bands were demonstrated by agarose-gel electrophoresis in all the donor and corresponding transcipient strains but plasmids were not found in the recipient strains or in strains cured of resistance. Plasmid-mediated transferable antiobiotic resistance in Bacteroides spp. may compromise the treatment of infections and may provide a reservoir of antibiotic resistance in the intestinal flora.