What is true community-acquired urinary tract infection? Comparison of pathogens identified in urine from routine outpatient specimens and from community clinics in a prospective study.

In order to identify the true nature of community-acquired urinary tract infections, the uropathogens isolated from 100 patients with urinary tract infection included in a prospective study conducted in community clinics were compared to 244 isolates from outpatient urine specimens routinely submitted to the laboratory. Significant differences in both the spectrum of bacteria and their antibiograms were found between the two groups. Laboratory data analysis of uropathogens from outpatient urine specimens may not reflect the true bacteriology of urinary tract infections acquired in the community. Hence, surveys based on laboratory data alone may overestimate resistance rates, leading to misinformed choices being made when treatment is empirical.

Interventions for treating melioidosis.

BACKGROUND: Melioidosis is an infectious disease that occurs in tropical regions, particularly in Thailand. It is caused by the bacterium Burkholderia pseudomallei and is a serious condition which can be fatal. Beta-lactam antibiotics have dramatically reduced the risk of death, but mortality still remains high. OBJECTIVES: To summarize reliable evidence on the effects of treatment regimens on death and relapse. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group trials register (July 2002), the Cochrane Controlled Trials Register (Issue 3, 2002), MEDLINE (1966 to July 2002), EMBASE (1980 to May 2002), BIOSIS (up to July 2002), Health Star (up to July 2002), and reference lists of articles. We also contacted pharmaceutical companies and researchers in the field. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials comparing antibiotic regimens in people with melioidosis. DATA COLLECTION AND ANALYSIS: We independently assessed the eligibility of studies and the methodological quality of the trials. Adverse effects information was collected from the trials. MAIN RESULTS: Nine trials, all from Thailand, involving a total of 872 participants were included. For intravenous therapy in the acute phase, we identified six trials with a total of 619 participants. Chloramphenicol, doxycycline, and co-trimoxazole (trimethoprim-sulphamethoxazole) combination regimens were associated with a mortality of 50% or more (two studies). Participants randomized to regimens including ceftazidime were more likely to survive (relative risk [RR] 0.46; 95% confidence interval [CI] 0.30 to 0.71). When ceftazidime-containing regimens were compared with beta-lactam or alternative beta-lactamase inhibitor regimens such as co-amoxiclav (amoxycillin-clavulanic acid) and cefoperazone-sulbactam, or with imipenem, mortality rates were similar (RR 1.06; 95% CI 0.81 to 1.39). For oral therapy in the maintenance phase, we found three trials of 253 participants. They compared the conventional regimen (chloramphenicol, doxycycline, and trimethoprim-sulphamethoxazole) with other regimens (amoxycillin-clavulanic acid, ciprofloxacin-azithromycin, and doxycycline alone). There were fewer deaths with the conventional regimen, but no statistically significant differences demonstrated. REVIEWER'S CONCLUSIONS: Regimens for the acute phase of illness should contain ceftazidime or imipenem. It is not yet clear if combinations of treatments in the early phase reduce relapse. For oral therapy after the acute phase of treatment, trials suggest that conventional four drug regimens can be used for treatment.

Interventions for treating melioidosis.

BACKGROUND: Melioidosis is an infectious disease caused by a bacterium (Burkholderia pseudomallei) found particularly in some areas in the tropics. It is a serious condition which can be fatal. Beta lactam antibiotics have dramatically reduced the risk of death, but mortality still remains high. OBJECTIVES: To summarise evidence from randomised trials on the effects of treatment regimens on death and relapse. SEARCH STRATEGY: Cochrane Controlled Trials Register, MEDLINE, EMBASE, BIOSIS from 1966 to September 2000 using MeSH terms "pseudomallei", "melioidosis" together with the terms "randomized-controlled-trial", "random allocation"; reference lists in articles on melioidosis; contact with trialists. SELECTION CRITERIA: Randomised and quasi-randomised trials assessing treatments in patients with melioidosis. DATA COLLECTION AND ANALYSIS: Eligibility and trial quality was assessed by two reviewers independently. MAIN RESULTS: For intravenous therapy in the acute phase, we identified five trials with a total of 519 patients. Chloramphenicol, doxycycline, and co-trimoxazole (trimethoprim-sulphamethoxazole) combination regimens were associated with a mortality of 50% or more (two studies). Patients randomised to regimens that included ceftazidime were more likely to survive (relative risk [RR] 0.46, 95% confidence interval [CI] 0.30 to 0.71). When ceftazidime-containing regimens were compared with beta lactam or alternative beta lactamase inhibitor regimens such as co-amoxiclav (amoxycillin-clavulanic acid) and cefoperazone-sulbactam, mortality rates were similar (RR 1.10, 95% CI 0.83 to 1.46), as was the case in one trial of imipenem. For oral therapy in the maintenance phase, we found two trials of 188 participants. Results showed that treatment with the conventional regimen (chloramphenicol, doxycycline, and trimethoprim-sulphamethoxazole) resulted in fewer fatalities in patients compared to a regimen of amoxycillin-clavulanic acid and doxycycline alone. REVIEWER'S CONCLUSIONS: Regimens for the acute phase of illness should contain ceftazidime or imipenem. It is not yet clear if combinations of treatments in the early phase reduce relapse. For oral therapy after the acute phase of treatment, trials suggest that conventional four drug regimens can be used for treatment.

Hospital acquired pneumonia in the medical intensive care unit--a prospective study.

AIM OF STUDY: The aim of the study was to define the prevalence, risk factors, spectrum of organisms and sensitivity patterns, and the outcome in patients with severe hospital acquired pneumonia (HAP) in the Medical Intensive Care Unit (SCU) in a hospital in Singapore. METHOD: Consecutive patients admitted to the MICU over a 6-month period were studied and assessed daily to determine whether patients had developed HAP based on defined clinical criteria. Sputum or endotracheal aspirate was obtained and results recorded from each patient on admission and every subsequent three days throughout the stay in the MICU. Mortality during hospital stay was the main outcome measure recorded. RESULTS: A total of 136 patients (150 admissions) were studied; 24 patients were identified as having HAP. The prevalence of HAP was 17% [both ventilator-associated pneumonia (VAP) and pneumonia acquired from the ward (WAP)]. Cerebral disease was the main risk factor for VAP (OR 4.94, 95% CI 1.33-18.4). The spectrum of organisms which caused HAP were polymicrobial, Klebsiella pneumoniae, Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus and coagulase negative Staphylococcus. The mortality of patients with VAP and WAP were 72.7% and 76.9% respectively. CONCLUSION: This study concludes that HAP in the MICU is common with a high mortality. The spectrum of organisms was comparable to previous studies.

The athlete's heart: is this an entity in paediatrics?

A case report of a boy who demonstrates features of an athlete's heart, associated with dilatation of the coronary artery, is presented. The importance of distinguishing this benign condition from pathologic causes such as cardiomyopathy, and risk of sudden death in these athletes is discussed.

Necrotizing fasciitis--an unusual presentation of miliary mycobacterium tuberculosis.

We report an immunocompromised patient who presented with necrotizing fasciitis as the initial presentation of miliary tuberculosis. The diagnosis of miliary tuberculosis was delayed resulting in prolonged morbidity and hospital stay. The lesson from this report is that tuberculosis should be recognised as an uncommon cause of necrotizing fasciitis in an immunocompromised patient, especially if the response to prompt and standard initial treatment is unsatisfactory.

Disposition of intravenous metronidazole in Asian surgical patients.

Steady-state peak and trough concentrations of metronidazole and its metabolites were measured in the sera of 54 surgical patients who were on intravenous metronidazole, 500 mg every 8 h. These patients had no significant renal or hepatic impairment. High-pressure liquid chromatography was used to determine the concentrations of metronidazole and its metabolites. The mean peak and trough metronidazole concentrations were 28.9 +/- 11.0 and 18.0 +/- 9.9 micrograms/ml, respectively. The acid metabolite was not detectable in all the blood specimens. The mean peak concentration of the hydroxy metabolite (MH) was 6.6 +/- 4.3 micrograms/ml, the mean trough concentration of MH was 6.2 +/- 4.2 micrograms/ml, and the MH concentration/metronidazole concentration ratio was 0.4 +/- 0.24. Using a population-based method for the pharmacokinetic analysis and stepwise regression between parameters and covariables (sex, age, and weight), we found that weight showed the highest correlation with the total body clearance (CL). The mean CL was 0.89 +/- 0.3 ml min-1 kg-1 (3.029 liters/h), the mean volume of distribution was 0.73 +/- 0.14 liter/kg, and the mean elimination half-life was 10.6 +/- 4.5 h. For the patients in our study, the CL was lower and the elimination half-life was longer compared with those for healthy volunteers, but the values of these parameters were comparable to those found for hospitalized patients. There was an inverse correlation between age and CL.

Paracetamol and its metabolites in saliva and plasma in chronic dialysis patients.

1. Many pharmacokinetic studies on paracetamol are based on saliva paracetamol concentrations. The utility of saliva in patients with chronic renal failure is unclear. In this study, concentrations of saliva and plasma paracetamol and its major metabolites, sulphate and glucuronide conjugates were determined at 0.5, 1, 2 and 3 h after the ingestion of 1 g paracetamol in 20 patients with endstage renal failure. Ten haemodialysis patients were studied on a non-haemodialysis day and during a haemodialysis session. The other 10 patients were on chronic ambulatory peritoneal dialysis. 2. The plasma paracetamol concentrations attained in all groups were not different from those reported previously in healthy subjects. Mean +/- s.d. plasma paracetamol concentrations at 0.5 h in haemodialysis patients on a non-haemodialysis day, during haemodialysis and in those on chronic ambulatory peritoneal dialysis were 15.3 +/- 8.2, 21.5 +/- 10.9 and 18.2 +/- 12.3 micrograms ml-1 respectively. 3. The saliva paracetamol concentrations were highly variable and unpredictable. Saliva paracetamol concentrations at 1, 2 and 3 h after ingestion in the haemodialysis group during haemodialysis were 31.5 +/- 20.1, 14.1 +/- 10.4 and 7.3 +/- 3.8 micrograms ml-1 respectively, significantly (P < 0.05; paired t-test) higher than the corresponding plasma paracetamol concentrations which were 11.0 +/- 2.8, 6.5 +/- 2.8 and 3.2 +/- 0.9 micrograms ml-1 respectively. 4. Correlation coefficients between saliva and plasma paracetamol concentrations in haemodialysis patients on a non-haemodialysis day and during haemodialysis and in chronic ambulatory peritoneal dialysis patients were poor; r = 0.58 (P < 0.0002); r = 0.40 (P < 0.02); and r = 0.13 (P = 0.49) respectively. 5. Three hours after paracetamol ingestion, plasma paracetamol, sulphate and glucuronide concentrations were significantly (P < 0.05) reduced in haemodialysis patients during haemodialysis when compared with the same patients on a non-haemodialysis day (paired t-test) and to the chronic ambulatory peritoneal dialysis group (Kruskal-Wallis ANOVA) except for plasma glucuronide. This indicates the effective removal of paracetamol and metabolites by haemodialysis. In contrast, chronic ambulatory peritoneal dialysis seemed to remove glucuronide only. 6. In the light of the poor correlation between saliva and plasma paracetamol in dialysis patients in this study, we would like to caution against using saliva paracetamol concentrations for pharmacokinetic studies in this group of patients.

Tuberculosis and invasive pulmonary aspergillosis in a young woman with a myelodysplastic syndrome.

A 29-year-old Chinese woman developed pyrexia, multiple skin abscesses and bilateral fine nodular lung infiltrates about 3 months after the commencement of therapy for idiopathic thrombocytopenic purpura (ITP). Pseudomonas aeroginosa was isolated from the abscesses but multiple blood and sputum cultures, as well as a broncho-alveolar lavage did not yield any microorganisms. The persistence of fever and pulmonary infiltrates warranted an open lung biopsy which provided a definitive diagnosis of tuberculous-aspergillus granulomatous lung disease. Bone marrow re-examination revised the primary haematological disorder to that of a trisomy 8 associated myelodysplastic syndrome.

Antimicrobial resistance problem in a university hospital.

In a study conducted in 1991 in the National University Hospital, Singapore, the susceptibilities of a total of 2156 recent clinical isolates were tested against 25 antimicrobial drugs. The organisms were those isolated from routine specimens received in the microbiology laboratory. About 40% Staphylococcus aureus isolations in the hospital were resistant to methicillin. A high incidence of the resistance was noted among Staphylococcus aureus and coagulase negative staphylococci to antistaphylococcal drugs. Acinetobacter sp. and Klebsiella sp. are becoming major threats with regard to antimicrobial treatment as they are multi-drug resistant. Pseudomonas aeruginosa did not show a resistance problem except to pefloxacin (74%). Ampicillin resistance of Acinetobacter sp. (93%) was reduced to 71% by ampicillin/clavulanic acid and to 7% by ampicillin/sulbactam. With regards to the urinary isolates higher rates of resistance were noticed with Pseudomonas aeruginosa to antipseudomonas drugs and for co-trimoxazole with other Gram negative organisms, compared to non-urinary isolates.

Nonfatal and fatal infections caused by Chromobacterium violaceum.

Human infection caused by Chromobacterium violaceum is rare, but when it occurs it is associated with a high mortality rate. We report the cases of two patients with infection due to Chromobacterium violaceum. One patient presented early in the course of disease and survived after receiving appropriate antibiotic therapy. The other patient presented late in the course of disease and died of fulminant sepsis with abscesses in multiple organs. We discuss the similarity between C. violaceum infection and the septicemic form of melioidosis.

The role of the doctor in drug safety.

The safe use of drugs is the collective responsibility of the doctor, the patient and the pharmaceutical industry. The risk of adverse drug reactions though not totally preventable, can be minimised. The doctor can help to decrease the frequency and severity of adverse drug reactions by observing the basic principles of "good prescribing", namely: (i) the benefits of drug therapy should outweigh the risks of adverse drug reactions; (ii) individualization of drug therapy; and (iii) monitoring efficacy and adverse reactions.

Paracetamol elimination in Chinese and Indians in Singapore.

The 24 h urinary excretion of paracetamol and its conjugates after oral administration of about 15 mg/kg was studied in 24 Chinese and 24 Indian healthy young adult male volunteers living in Singapore. The Indians excreted a significantly lower fraction of sulphate conjugate (28.9% compared to 35.9% in the Chinese), and a correspondingly higher fraction as glucuronide conjugate (62.2% compared to 54.5% in the Chinese). There was no difference between the ethnic groups in terms of the urinary recovery of unchanged paracetamol (Indians 3.4%, Chinese 3.6%), glutathione-derived cysteine (Indians 2.3% and Chinese 2.2%) and mercapturic acid (Indians 3.6%, Chinese 3.8%) conjugates. The total fraction of administered paracetamol recovered in the urine was 84.7% and 85.7% in the Indian and the Chinese groups, respectively. Although the total glutathione derived conjugates recovered in the two ethnic groups were similar (Indians 5.9%, Chinese 6%), the values were lower than those reported previously for Caucasians in Scotland (9.3%).

Adverse drug reactions: an integrated approach.

The need for early detection and a better understanding of adverse drug reactions (ADRs) is well recognized today. This paper describes an approach to the study of ADRs characterized by the integration of pharmacoepidemiology, clinical pharmacology and molecular/cellular biology (pharmacogenetics). Merging of these disciplines would greatly enhance our approach to unanticipated drug toxicity and would narrow the risk/benefit margin of pharmacotherapeutic interventions. Such an integrative strategy is a key element in any initiative directed toward the promotion of optimal drug therapy. (Ref. 16.)

Serodiagnosis of melioidosis in Singapore by the indirect haemagglutination test.

Melioidosis is endemic in Singapore, with diagnosis dependent upon both bacteriological culture and serodiagnosis. Using the polysaccharide (melioidin)-sensitized turkey red cells in the indirect haemagglutination test (IHAT), 20 (100%) of the Pseudomonas pseudomallei culture-positive cases were detectable by the IHAT with titles ranging from 1:16 to 1:32, 768. Eight of these patients who died within a few days after the IHAT was performed had titres ranging from 1:16 to 1:1028. Five culture-negative patients, with clinical symptoms suggestive of melioidosis infection and who responded to treatment with ceftazidime, showed IHA titres between 1:64 and 1:8,192. One hundred and twenty one sera from patients with pneumonia, abscesses, or diabetes mellitus were IHAT negative. The IHAT showed good specificity since negative titres were seen in tests using sera from 2 patients with culture-positive Pseudomonas aeruginosa and 4 patients positive for Legionella. IHAT negative results were obtained from tests of 50 normal blood donors and 50 sewerage workers. Of 683 national servicemen tested, 5 (0.73%) had IHAT titres ranging from 1:16 to 1:128. Unlike hyperendemic areas such as Thailand where interpretation of IHAT is seriously hampered by IHA titres found in one-third to half of the population, serodiagnosis of melioidosis by the sensitive IHAT may be employed in Singapore as a routine procedure since background IHA titres are low.

Pasteurella multocida osteomyelitis of the cervical spine in a patient on chronic haemodialysis.

Osteomyelitis due to Pasteurella multocida has been frequently documented but virtually all previous cases have resulted from direct inoculation of the organism or contiguous spread of local infection, following animal bites or scratches. Infections often occur in patients with serious underlying illnesses. Haematogenous osteomyelitis due to P multocida has very rarely been reported particularly in patients with chronic renal failure. We describe a patient on chronic haemodialysis who developed an acute febrile illness, two months following a monkey bite, caused by haematogenous cervical vertebral osteomyelitis due to P multocida.

Serum digoxin concentration in a neonate with renal and hepatic impairment.

This report demonstrates the questionable usefulness of monitoring digoxin concentrations using the available immunoassays in some clinical situations. The patient reported here showed three characteristics (being a neonate with hepatic and renal impairment) that are associated with the presence of digoxin-like immunoreactive substances. The patient's serum digoxin concentration continued to rise to a peak of 43.7 nmol/L (34.1 ng/mL), 19 days after administration of the drug was discontinued.

Pharmacokinetics of intravenous vancomycin in patients with end-stage renal failure.

The pharmacokinetics of a 500-mg dose of i.v. vancomycin were studied in six Chinese patients with end-stage renal failure. Serum vancomycin concentrations were determined by high-performance liquid chromatography. Observed peak and trough (at 168 h postinfusion) concentrations were in the range of 14.2-35.0 micrograms/ml and 2.8-5.5 micrograms/ml, respectively. The data were analyzed using the PCNONLIN. In all six patients, the data could be fitted well by both the biexponential and triexponential models, but in three patients the latter model provided a better fit. Two-compartment pharmacokinetic parameters obtained from the six patients were t 1/2 alpha 1.13 +/- 0.25 h (mean +/- SEM), t 1/2 beta 121.3 +/- 8.2 h, Vc 0.45 +/- 0.09 L/kg, Vss 1.00 +/- 0.12 L/kg, ClT 5.90 +/- 0.69 ml/kg/h, and the calculated Cmax 25.0 +/- 6.1 micrograms/ml. The mean vancomycin serum protein binding was 18.5 +/- 12.0% as compared with a mean of 46.0% in pooled serum from normal controls. Hemodialysis had no significant effect on vancomycin protein binding or clearance. On the basis of our kinetic study, 500 mg of vancomycin given every seven days is probably adequate treatment for methicillin resistant Staphylococcus aureus infection in end-stage renal failure patients, but further clinical studies are necessary to confirm this.

Population pharmacokinetics of phenytoin in Singapore Chinese.

The pharmacokinetics of phenytoin was studied in 66 epileptic Chinese children and adults. The data were analysed by the population approach, using the non-linear mixed effect model, in the MULTI (ELS) program. There was no age or gender-related effect on either the apparent maximum elimination rate (kmax) or Michaelis-Menten constant (KM). Kmax was related to body weight 0.656. The population pharmacokinetics was similar in children and adults. Kmax and KM were estimated to be 30.72 mg.kg-0.656 day-1 and 2.307 mg.l-1, respectively. Kmax was higher than reported values, and KM was comparable to that reported in a study in Japanese, but was much lower than that reported in studies of European patients. The inter-individual variability of KM (CV 65.58%) was substantially higher than that of kmax (CV 28.49%), and the residual (intra-individual) variability was found 21.33% (CV).

Murine typhus infection complicated by dengue haemorrhagic fever.

Murine typhus is endemic in many South East Asian countries but it has not been reported from the island of Borneo. Recently we attended to an English lady who contracted the disease in Brunei. Her clinical course unexpectedly turned stormy in the third week of the illness accompanied by severe thrombocytopenia. She made a complete recovery. Serological studies here and subsequently in England confirmed that she suffered from recent murine typhus infection complicated by dengue haemorrhagic fever.