Distribution of CBP genes in Streptococcus pneumoniae isolates in relation to vaccine types, penicillin susceptibility and clinical site.

Choline-binding proteins (CBP) have been associated with the pathogenesis of Streptococcus pneumoniae. We screened, using PCR, for the presence of genes (cbpA, D, E, G) encoding these proteins in 34 isolates of pneumococci of known serotypes and penicillin susceptibility from invasive and non-invasive disease. All isolates harboured cbpD and cbpE whereas cbpA and cbpG were found in 47% and 59% respectively; the latter were more frequent in vaccine-associated types and together accounted for 77% of these isolates. No association was observed with penicillin susceptibility but 85% of non-invasive isolates were positive for these genes.

Invasive meningococcal disease in the University of Malaya Medical Centre, Kuala Lumpur, Malaysia.

BACKGROUND: Neisseria meningitidis (N. meningitidis) remains the leading worldwide cause of acute bacterial meningitis and fatal sepsis in healthy individuals. MATERIALS AND METHODS: A total of 12 cases of N. meningitidis from patients with invasive meningococcal infections in University of Malaya Medical Centre, Kuala Lumpur during the years 1987-2004 were reviewed together with details of age, sex, disease, risk factors treatment and outcome of these patients. RESULTS: Their ages ranged from 10 months to 64 years (median age 29.75 years). The male to female ratio was 1.42:1. Fever, neck stiffness, headache, vomiting and confusion were predominant symptoms. Upper respiratory tract viral infection and Hajj pilgrimage were directly associated with invasive meningococcal disease. Penicillin or ceftriaxone or both in some cases were administered as empirical therapy. All isolates were sensitive to penicillin, ceftriaxone, chloramphenicol and rifampicin. The case fatality ratio was 1:4. One Hajj pilgrim died despite having received polyvalent meningococcal vaccine. Amongst the survivors, two patients had neurological deficit, hearing loss and arthritis. CONCLUSION: Early antimicrobial therapy has been shown to reduce these adverse outcomes. Clinicians need to be alerted to the presence of the disease in the community and the disease should be made notifiable within 24 hours of detection both for early treatment of cases and to facilitate contact tracing, institution of prophylactic treatment and prevention of secondary cases.

Faecal prevalence of extended-spectrum Beta-lactamase (ESBL)-producing coliforms in a geriatric population and among haematology patients.

Antimicrobial resistance to the extended-spectrum cephalosporins is increasingly reported worldwide. In the local setting, nosocomial infections with multi-resistant Gram-negative bacilli are not uncommon and are a growing concern. However, there is limited data on the carriage rates of such organisms in the local setting. In May 2001, a prospective study was carried out to determine the enteric carriage rates of ceftazidime-resistant Gram negative bacilli (CAZ-R GNB) among residents of nursing homes and from in-patients of the geriatric and adult haematology wards of University Malaya Medical Centre. Ceftazidime-resistant Gram-negative bacilli (CAZ-R GNB) were detected in 25 samples (30%), out of which 6 were from nursing home residents, 5 from geriatric in-patients and 14 from the haematology unit. A total of 28 CAZ-R GNB were isolated and Escherichia coli (10) and Klebsiella pneumoniae (7) were the predominant organisms. Resistance to ceftazidime in E. coli and Klebsiella was mediated by extended-spectrum beta-lactamases (ESBLs). Although the majority of the CAZ-R GNB were from patients in the haematology ward, the six nursing home residents with CAZ-R GNB were enteric carriers of ESBL-producing coliforms. Prior exposure to antibiotics was associated with carriage of ESBL organisms and to a lesser extent, the presence of urinary catheters.

Antimicrobial susceptibility and distribution of non-typhoidal Salmonella serovars isolated in Malaysian children.

There is widespread resistance of Salmonella species to commonly prescribed antimicrobials the world over. We aimed to determine the antimicrobial susceptibility and serovar distribution of non-typhoidal Salmonella (NTS) isolated from blood cultures of Malaysian children. Positive isolates of NTS from blood cultures obtained from children admitted to the pediatric wards of University of Malaya Medical Center (UMMC), a large urban hospital from Kuala Lumpur (1991-2001), and Hospital Kota Bharu (HKB), from the predominantly rural state of Kelantan (1991-1999), Malaysia, were reviewed retrospectively. Serovar distribution and antimicrobial susceptibility were ascertained. A total of 64 and 55 isolates of NTS were obtained from blood cultures of children admitted to UMMC and HKB, respectively. The commonest serovar isolated was Salmonella enteritidis in both centers. The NTS isolated were highly sensitive to the antimicrobials tested: ampicillin 98 per cent, chloramphenicol 98 per cent, gentamicin 97 per cent, trimethoprim-sulfamethoxazole (TMP-SMX) 98 per cent, and ceftriaxone 100 per cent in UMMC; ampicillin 100 per cent, chloramphenicol 87 per cent, kanamycin 100 per cent, streptomycin 96 per cent, TMP-SMX 93 per cent, and tetracycline 89 per cent in HKB. There were only one and five multi-resistant isolates in UMMC and HKB, respectively. In conclusion, NTS isolated from blood cultures of Malaysian children from Kuala Lumpur and Kota Bharu were highly sensitive to commonly prescribed antibiotics. We speculate that this is due to the restriction of sales of antimicrobials in Malaysia except by prescription. Continuing vigilance and frequent antmicrobial surveillance is necessary.

The racial cohort phenomenon: seroepidemiology of Helicobacter pylori infection in a multiracial South-East Asian country.

BACKGROUND: Malaysia is a multiracial country where three major Asian races live together: Malay, Chinese and Indian. In addition, there are a number of native or indigenous races, particularly in East Malaysia. Differences in prevalence of gastric diseases between races have been noted, particularly with respect to peptic ulcer disease and gastric cancer. The aim of this study is to determine the prevalence rates and risk factors for Helicobacter pylori infection among various races in Malaysia. METHODS: A large-scale prospective seroepidemiological study in West and East Malaysia using the HEL-p II commercial enzyme-linked immunosorbent assay kit (AMRAD, Melbourne, Australia) to detect H. pylori antibodies. Populations surveyed in West Malaysia were a rural community from Kuala Pilah, and blood donors from Kuala Lumpur and Kota Baru. Subjects studied in East Malaysia were volunteer blood donors from Kota Kinabalu, and blood donors and healthy volunteers from Sibu. Statistical analyses using multiple logistic regression analysis were carried out to identify independent risk factors for H. pylori infection RESULTS: A total of 2,381 subjects were evaluated. H. pylori prevalence varied from different areas of study and ranged from a low of 26.4% in blood donors from Kota Baru to a high of 55.0% in Kota Kinabalu. The most striking differences, however, were noted in the prevalence rates among different racial groups. Prevalence rates among the Malays ranged from 11.9 to 29.2%, while the Chinese ranged from 26.7 to 57.5%, and those of Indians in two studies were 49.4 and 52.3%. In every location, Malays had a significantly lower prevalence compared with the other races. The highest prevalence rates were recorded among the indigenous races in Kota Kinabalu, East Malaysia. There was no difference between males and females in the studies. An increasing trend with age was noted in the majority of studies; however, no increase in prevalence rates was noted among the Malays. CONCLUSIONS: The pattern of infection in a multiracial population in Malaysia points to a 'racial cohort' phenomenon. The infection appears to be confined to a racial group, with the Malays having consistently low prevalence rates. This observation may provide clues to the mode of transmission of infection.

Comparison of three different methods for the presumptive detection of ESBL production in ceftazidime-resistant strains of Klebsiella pneumoniae.

Twenty-eight (28) strains of ceftazidime-resistant Klebsiella pneumoniae were isolated from blood cultures of in-patients from University Hospital, Kuala Lumpur between March 1995 and August 1996. Three methods were used to detect the production of ESBL enzymes by these strains. These three methods include the double-disc synergy test (DDST), inhibitor-potentiated disc-diffusion test (IPDD) and the E-test ESBL method. All strains could be identified as ESBL producers using the DDST method by a minimum of two beta-lactams and these included either a combination of ceftazidime and ceftriaxone with clavulanate respectively or cefotaxime and aztreonam with clavulanate respectively. Similarly using a combination of either cefotaxime and ceftriaxone with clavulanate or ceftriaxone and aztreonam with clavulanate respectively would have detected all strains as ESBL producers. The IPDD method could also detect for ESBL activity based on combinations of beta-lactam antibiotics with clavulanate respectively. All combinations of beta-lactam antibiotics could detect for ESBL activity in all the strains except a combination of either ceftazidime and aztreonam or cefotaxime and ceftriaxone with clavulanate respectively. The E-Test method using ceftazidime alone and in combination with clavulanate was found to be the most effective method in the presumptive identification of ESBL activity in all the strains.

Efficacy of a 1-week pantoprazole triple therapy in eradicating Helicobacter pylori in Asian patients.

BACKGROUND: The aim of the present paper was to determine the efficacy and tolerability of a 1-week treatment regimen consisting of pantoprazole and two antibiotics: clarithromycin and amoxycillin, in the eradication of Helicobacter pylori. METHODS: The patients selected had unequivocal evidence of H. pylori infection based on urease test, culture and histology on antral and corpus biopsies obtained at endoscopy. Patients received pantoprazole 40 mg twice a day, clarithromycin 500 mg twice a day and amoxycillin 1 g twice a day for 1 week and were assessed for successful eradication at least 4 weeks after completion of therapy by repeat gastroscopy and gastric biopsies. Eradication was defined as absence of bacteria in both antral and corpus biopsies tested by culture, histology and urease test. RESULTS: One hundred and six patients were recruited for the study. The mean age was 48.0 years (range: 23-74 years). Four patients defaulted follow up and five patients were not compliant (taking less than 85%) with medications. Eradication rates on per-protocol analysis were: 88/97 (90.7%; 95% CI: 83.1-95.7); and on intention-to-treat analysis they were: 88/106 (83.0%; 95% CI: 75.9-90.2). Side-effects were in general mild and tolerable: 57 of 106 (53.7%) patients complained of a bitter taste; 15 (14.1%) complained of giddiness; 10 (9.4%) complained of increased abdominal pain; 11 (11.5%) complained of lethargy and 16 (15.1%) complained of loose motions. Pre-treatment metronidazole resistance was encountered in 57/74 strains (77.0%). Clarithromycin resistance was not encountered in any of the strains. CONCLUSIONS: The pantoprazole 1-week triple therapy with amoxycillin and clarithromycin is effective in H. pylori eradication. The treatment was well tolerated by patients. Metronidazole resistance was reported in a high percentage of strains isolated from patients. Clarithromycin resistance was, however, not detected in any of the strains.

Extra-intestinal non-typhoidal Salmonella infections in children.

Extra-intestinal non-typhoidal Salmonella (NTS) infections are uncommon in developed countries but common in developing ones. The risk factors, clinical features and outcome of children admitted to the Department of Paediatrics, University of Malaya Medical Center, Kuala Lumpur from 1978 to 1998 with extra-intestinal NTS infections were reviewed. All positive cultures of NTS, blood, cerebrospinal fluid, urine, synovial, pericardial and other body secretions (except stools), were included. Of the 98 cases reviewed, 56 were boys and 42 girls. The mean age was 2.1 years (range: newborn to 14 years). Twenty-seven children were severely immunocompromised and 21 had underlying chronic medical disorders. Bacteraemia was the most commonly detected type of infection and meningitis the commonest focal infection. The overall mortality rate was 15%. An immunocompromised state or underlying chronic medical disorder was associated with increased mortality. The three serotypes most commonly isolated were S. enteritidis, S. paratyphi B and S. typhimurium. Most isolates were sensitive to antibiotics commonly used in salmonellosis.

Seroprevalence of Helicobacter pylori infection in Malaysian children: evidence for ethnic differences in childhood.

OBJECTIVES: To determine the prevalence of Helicobacter pylori (H. pylori) in healthy Malaysian children and to discover whether differences exist among children of different races. METHODS: Serum samples from asymptomatic children tested for H. pylori seropositivity using an ELISA test. RESULTS: Five hundred and fourteen healthy urban Malaysian children aged 0.5 to 17 (mean 5.9) years from three different racial groups had their blood tested for H. pylori antibodies. The overall prevalence was 10.3%. There was no significant difference in the prevalence of infection between boys and girls, but a significant rise was noted with increasing age (P = 0.009). Seropositivity was most common in the Indians and lowest in the Malays (P = 0.001). Father's level of education did not affect the child's rate of H. pylori seropositivity. CONCLUSION: The prevalence of H. pylori seropositivity among asymptomatic urban Malaysian children is lowest in Malays. Intermediate in Chinese and highest in Indians. The racial differences found in children are consistent with those found in Malaysian adults.

Bacterial infection of central venous catheters in short-term total parenteral nutrition.

Fourteen severely ill ventilated patients in an intensive care unit, requiring short-term total parenteral nutrition, were examined for catheter-related infection. Microbiological analysis using Maki's SQ technique was carried out on catheter exit site, catheter hub, proximal subcutaneous segment of catheter and catheter up. Qualitative cultures were carried out on total parenteral nutrition and peripheral blood samples. Twenty six of 29 catheters removed (90%) were culture positive but only 7 catheters were related to positive blood cultures, giving a catheter-related bacteremia (CRB) rate of 24%. Haematogenous seeding was strongly implicated in 7/29 (24%) of catheters. Patients' skin flora appeared to be the main source of catheter-related infection. The organisms isolated for patients with CRB included coagulase-negative staphylococci, Acinetobacter and Klebsiella. It is suggested that to control infective complications of central venous catheters, emphasis should be focused on specialised intravenous therapy teams and the use of strict protocols for insertion and care of central lines.

Management of Helicobacter pylori infection--a Working Party Report of the Malaysian Society of Gastroenterology and Hepatology.

The Working Party Report on the Management of Helicobacter pylori serves as a clinical practice guideline for Malaysian doctors. H. pylori is not uncommon in the Malaysian population. Marked racial differences and the consistently low prevalence rates amongst Malays are noted. The working party recommends that if endoscopy is to be performed, a rapid urease test should be used for diagnosis. Where suspicion of the infection is strong and the urease test is negative, histology should be performed on gastric biopsies. Culture should be used to monitor resistance patterns to antibiotics and regional laboratories should assume this responsibility. The urea breath tests are highly accurate tests for diagnosis of H. pylori but is as yet not widely available in Malaysia. The working party strongly recommends that all peptic ulcer patients infected with H. pylori whether active, in remission and complicated ulcers should be treated for the infection. Patients with low-grade gastric mucosal lymphoid tissue lymphoma should also be treated for H. pylori infection. It is considered advisable that patients on long term nonsteroidal antinflammatory drug (NSAID) treatment with a history of peptic ulcers or dyspepsia and patients following resection of early gastric cancer or those with a family history of gastric cancer should also be tested and treated for H. pylori. The working party recommends, as first line treatment a 7-day combination therapy of a proton pump inhibitor, clarithromycin and metronidazole or amoxicillin. High metronidazole resistance rates locally may adversely affect regimens containing the antibiotic. It should also be noted that regimens that yield lower eradication rates may result in higher long term expenditure.

Septicaemia in paediatric cancer patients: a 5-year surveillance study in university hospital, Kuala Lumpur, Malaysia.

Infectious complications are the major cause of morbidity and mortality in children with malignancy. Empirical antimicrobial therapy in the management of fever of unknown origin should be tailored to local bacteriological data and antibiotic sensitivity patterns. Five-hundred-and-fifty-nine cases of culture-proven septicaemia occurring in pediatric cancer patients between 1990 and 1994 were retrospectively analysed and compared with a similar study done in our centre between 1976 and 1979. A wide spectrum of organisms was isolated. Staphylococcus epidermidis, Staphylococcus aureus, and Klebsiella pneumoniae were the most common and consistent bacteria isolated during the 5 year period. More than 70 per cent of the staphylococci were sensitive to methicillin and universally sensitive to vancomycin. However, a worrying trend of ceftazidime-resistance amongst gram-negative organisms was found. In these situations, the use of imipenem is recommended as resistance to this antimicrobial agent was exceedingly rare.

Group B streptococcus: maternal carriage rate and early neonatal septicaemia.

Between January 1984 and December 1994, 30 cases of early neonatal group B streptococcus (GBS) septicaemia were managed in the Neonatal Unit, University Hospital, Kuala Lumpur. Two neonates were outborn and 28 were inborn, giving an average annual incidence of neonatal GBS septicaemia of 0.4/1000 livebirths among inborn babies. In a separate survey over a three-month period, GBS genital carriage rate among 196 parturients was found to be 9.7%. Of the infants with GBS septicaemia, the mean gestational age was 37.5 +/- 3.8 weeks and the mean birthweight was 2540 +/- 716 g. Twelve (40%) were preterm infants and 14 (47%) were low birthweight infants. Male and female infants were almost equally affected. Prolonged rupture of membranes and maternal pyrexia accounted for only 5 (17%) and 3 (10%) of the cases respectively. Twenty-four (80%) neonates had onset of symptoms within 6 hours of life and respiratory symptoms were observed in 24 (80%) of the cases, while meningitis was uncommon. Six (20%) neonates died. Preterm and low birthweight infants had higher mortality than their term counterparts: 42% versus 6% and 36% versus 6% respectively. Of those who died, 4 (67%) required respiratory support right from birth and the mean time of onset of symptoms was 4 hours (range 0 to 21 hours) and the duration of survival was only 28.8 hours (range 12 to 38 hours). As the incidence of neonatal GBS septicaemia was low, mass screening and chemoprophylaxis for GBS were not recommended. All the GBS isolates were sensitive to penicillin and ampicillin, thus one of these antibiotics should be included in the antimicrobial therapy of septic neonates.

Characteristics of childhood diarrhea associated with enterotoxigenic Escherichia coli in Malaysia.

Amongst 107 diarrheal cases studied a bacterial agent was isolated from 71 (66%) cases of which 60 (85%) were due to a single agent and the remaining 11 (15%) were of mixed infections. Enterotoxigenic Escherichia coli (ETEC) was isolated from 65 cases. Other pathogens isolated included Salmonella spp, Shigella spp and rotavirus. There was a higher isolation rate of ETEC from females and rotavirus from males. The infection rate was found to higher for the 0-2 year age group as compared to the 3-5 year age group. Amongst the ETEC isolated the STa 2 toxotype was the predominant type.

Comparison of two 1-week low-dose omeprazole triple therapies--optimal treatment for Helicobacter pylori infection?

OBJECTIVES: To determine and compare the efficacy and tolerability of two 1-week regimen comprising omeprazole, clarithromycin and amoxycillin or metronidazole in the eradication of Helicobacter pylori, and to determine the influence of bacterial resistance to metronidazole and clarithromycin on the outcome of treatment. PATIENTS AND METHODS: Patients with unequivocal evidence of H. pylori infection based on culture, histology and rapid urease test of both antrum and corpus biopsies were recruited for the study. The study was a randomized, investigator-blind, comparative study. Patients received either omeprazole 20 mg o.m., clarithromycin 250 mg b.d. and amoxycillin 500 mg b.d. (OAC) or omeprazole 20 mg o.m., metronidazole 400 mg b.d. and clarithromycin 250 mg b.d. (OMC) for 1 week. Patients were assessed for successful eradication, which was defined as absence of bacteria in all tests (culture, histology and urease test on both antral and corpus biopsies), at least 4 weeks after completion of therapy. RESULTS: Eighty-two patients were recruited for the study. Eradication rates on intention-to-treat analysis were--OAC: 36/41 (87.8%, 95% CI: 73.8, 95.9); OMC: 33/41 (80.5%, 95% CI: 65.1, 91.2). On per protocol analysis were--OAC: 36/40 (90%, 95% CI: 76.3, 97.2); OMC: 32/38 (84.2%, 95% CI: 68.7, 94.0). All side-effects encountered were mild and no patient discontinued treatment because of intolerance to medications. The most common side-effects were altered taste (OAC 31.7%, OMC 53.7%) and lethargy (OAC 14.6%, OMC 19.5%). Pre-treatment metronidazole resistance was encountered in 34/63 (54.0%) patients. No bacterial strains were found with primary resistance to clarithromycin. Metronidazole resistance did not significantly affect eradication rates. Emergence of resistance to clarithromycin was not seen post-therapy. CONCLUSIONS: Both the OAC and the OMC regimens were convenient and well-tolerated treatments for H. pylori. However, eradication rates were lower than anticipated.

Combination amoxycillin and metronidazole with famotidine in the eradication of Helicobacter pylori--a randomized, double-blind comparison of a three times daily and twice daily regimen.

OBJECTIVES: To determine the efficacy of a three times daily (t.i.d.) versus a twice daily (b.i.d.) regimen of combination amoxycillin and metronidazole and famotidine in the eradication of Helicobacter pylori and the influence of metronidazole resistance on the outcome of treatment. PATIENTS: Patients selected had unequivocal evidence of H. pylori infection based on the urease test, culture and histology and had either peptic ulcer disease or non-ulcer dyspepsia. DESIGN: The study was a comparative and double-blind study and patients were randomized to receive either amoxycillin 750 mg t.i.d. and metronidazole 500 mg t.i.d. for 12 days or amoxycillin 1000 mg b.i.d. and metronidazole 500 mg b.i.d. for 12 days. Both groups also received famotidine 40 mg for 6 weeks. MAIN OUTCOME MEASURE: Patients were assessed for successful eradication, defined as absence of bacteria in all tests, at least 4 weeks after completion of antibiotic therapy by repeat gastroscopy. RESULTS: One hundred and twenty-nine patients were recruited for the study. Two patients defaulted follow-up, two patients were withdrawn from the study and six patients were found to be non-compliant with medications. The eradication rates of the t.i.d. regimen was higher than the b.i.d. regimen (per protocol (PP) analysis: 83.3% (50/60) vs. 76.3% (45/59), P=0.337; intention-to-treat (ITT) analysis: 78.5% (51/65) vs. 75.0% (48/64), P=0.642). Seventy-five patients had pre-treatment cultures checked for metronidazole resistance, 33 (44.0%) were found to be resistant. Acquired resistance occurred in 3/40 (7.5%) patients. Eradication rates of metronidazole-sensitive and metronidazole-resistant patients: t.i.d. regimen - 100% (17/17) and 88.2% (15/17), b.i.d. regimen - 19/21 (90.5%) and 11/15 (73.3%). Side effects were reported in up to 70% of patients but were mild and tolerable in the majority. Two patients were withdrawn from the study because of a fixed drug eruption in one and generalized macular rash in the other. CONCLUSION: Combination amoxycillin and metronidazole is effective in eradicating H. pylori. There was a tendency for the t.i.d. regimen to be better than the b.i.d. regimen and for metronidazole-resistant infections to be associated with a lower eradication rate but these differences did not reach statistical significance.

Does Helicobacter pylori infection affect gastric emptying in patients with functional dyspepsia?

The objectives of the study were first, to determine if gastric emptying was altered in patients with functional dyspepsia with and without Helicobacter pylori infection compared with normal healthy volunteers; and second, to determine if there were further alterations in gastric emptying when the infection was eradicated. Gastric emptying was measured using a 99mtechnetium radiolabelled solid meal and gastric emptying time was measured as t1/2, viz. time taken for half the radiolabelled meal to be emptied from the stomach. The mean gastric emptying time for H. pylori-positive patients (n=20) was 56.4+/-24.8 min; H. pylori-negative patients (n=19) 67.8+/-31.8 min; and normal controls (n=20) 58.8+/-18.8min. No significant difference was obtained between the groups (ANOVA; P=0.348). Thirteen of 18 H. pylori-positive patients successfully eradicated the infection following treatment with omeprazole 40 mg o.m. and amoxycillin 500 mg t.d.s. for 2 weeks. The mean difference in the gastric emptying time before and after H. pylori eradication was 23.9+/-13.2 min (P= 0.556). There was no significant difference in the frequency of specific dyspeptic symptoms as well as the overall mean symptom score between the H. pylori-positive and -negative patients. Gastric emptying was not different between patients with functional dyspepsia and normal controls. Helicobacter pylori infection does not appear to affect gastric emptying in patients with functional dyspepsia.

Emerging problems of antibiotic resistance in community medicine.

Emergence of antimicrobial resistance in bacteria associated with community acquired infections has made the choice of empirical therapy more difficult and more expensive. The problems due to possible spread of MRSA to the community, emergence of penicillin resistance in S. pneumoniae, ampicillin resistance in H. influenzae, and multiresistance among common enteric pathogens are highlighted. Bacteria have a remarkable ability to develop resistance to many of the newly synthesized antimicrobial agents but the appropriate use of antibiotics will delay and in many cases prevent the emergence of resistance.