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  1. Loh LC, Rosdara Masayuni MS, Nor Izran Hanim AS, Raman S, Thayaparan T, Kumar S
    Ann Acad Med Singap, 2007 Aug;36(8):642-6.
    PMID: 17767334
    INTRODUCTION: In Malaysia, Klebsiella pneumoniae ranks high as a cause of adult pneumonia requiring hospitalisation.

    PATIENTS AND METHODS: With concern over its rising microbial resistance, we explored the association of empiric antibiotics choices with the hospital outcomes of patients treated for microbial proven K. pneumoniae pneumonia in an urban-based teaching hospital.

    RESULTS: In 313 eligible cases reviewed retrospectively, hospital mortality and requirement for ventilation were 14.3% and 10.8% respectively. Empiric regimes that had in vitro resistance to at least one empiric antibiotic (n = 90) were associated with higher hospital mortality (23.3% vs. 10.8%, P = 0.004) with risk increased by about two-fold [Odds ratio (OR), 2.5; 95% confidence interval (CI), 1.3 to 4.8]. Regimes (n = 84) other than the commonly recommended "standard" regimes (a beta-lactam stable antibiotic with or without a acrolide) were associated with higher ventilation rates (16.7% vs. 8.8%, P = 0.047) with similar increased risk [OR, 2.0; 95% CI, 1.0 to 4.3].

    CONCLUSIONS: Our findings reiterate the clinical relevance of in vitro microbial resistance in adult K. pneumoniae pneumonia and support empiric regimes that contain beta-lactam stable antibiotics.

    Matched MeSH terms: Hospital Mortality
  2. Rushdan MN, Tay EH, Khoo-Tan HS, Lee KM, Low JH, Ho TH, et al.
    Ann Acad Med Singap, 2004 Jul;33(4):467-72.
    PMID: 15329758
    INTRODUCTION: The traditional indications for adjuvant pelvic radiotherapy (RT) for International Federation of Obstetrics and Gynecology (FIGO) stage Ib1 lymph nodes-negative cervix carcinoma following radical surgery based on histopathological factors, such as deep stromal invasion and lymphovascular space invasion (LVSI), were often inconsistently applied. The perceived risk of relapse was subjectively determined. This pilot study attempts to determine if the treatment outcome will be affected when the indication for RT is based on the Gynecologic Oncology Group (GOG) Risk Score (RS) and the field of adjuvant RT is tailored to the RS.

    MATERIALS AND METHODS: From 1997 to 1999, 55 patients with FIGO stage Ib1 lymph nodes-negative cervical carcinoma limited to the cervix were prescribed RT following radical surgery, based on their RS, as follows: RS <40, RT is omitted; RS >40 to <120, modified (smaller) field RT; and RS >120, standard field pelvic RT. Their incidence and site of recurrence were compared with a similar cohort of 40 patients who were treated prior to 1997.

    RESULTS: Prior to 1997, of the 40 patients, 10 patients were given standard field RT. There were 2 (5%) recurrent diseases. The mean duration of follow-up was 61.6 months (range, 1 to 103 months). The RS of 23 of the 30 patients who were not given RT were available. The mean RS was 22 with 5 patients having a score of >40. From 1997 onwards, of the 55 patients, 28 (51%) did not require RT, 13 (23%) were treated with modified (smaller) field RT and 14 (26%) were given standard field RT. There were 2 (3.6%) cases of relapse. The mean duration of follow-up was 36.4 months (range, 5 to 60 months). All patients with a RS of <40 did not suffer any relapse. Their survival outcomes were better when compared to patients who did not have any RT in the GOG Study.

    CONCLUSIONS: The results of this study indicated that postoperative adjuvant RT given to patients with a high GOG RS of >120, significantly improved their 5-year recurrence rate and disease-free survival, as compared with the similar group of patients who were without adjuvant therapy in the GOG study. Patients with a GOG risk-score of <40 may be safely spared from adjuvant pelvic RT. The current treatment protocol did not compromise the outcome in patients, compared with the use of a less precise treatment protocol in the past.

    Matched MeSH terms: Uterine Cervical Neoplasms/mortality
  3. Wong RS, Ismail NA, Tan CC
    Ann Acad Med Singap, 2015 Apr;44(4):127-32.
    PMID: 26041636
    INTRODUCTION: Intensive care unit (ICU) prognostic models are predominantly used in more developed nations such as the United States, Europe and Australia. These are not that popular in Southeast Asian countries due to costs and technology considerations. The purpose of this study is to evaluate the suitability of the acute physiology and chronic health evaluation (APACHE) IV model in a single centre Malaysian ICU.

    MATERIALS AND METHODS: A prospective study was conducted at the single centre ICU in Hospital Sultanah Aminah (HSA) Malaysia. External validation of APACHE IV involved a cohort of 916 patients who were admitted in 2009. Model performance was assessed through its calibration and discrimination abilities. A first-level customisation using logistic regression approach was also applied to improve model calibration.

    RESULTS: APACHE IV exhibited good discrimination, with an area under receiver operating characteristic (ROC) curve of 0.78. However, the model's overall fit was observed to be poor, as indicated by the Hosmer-Lemeshow goodness-of-fit test (Ĉ = 113, P <0.001). Predicted in-ICU mortality rate (28.1%) was significantly higher than the actual in-ICU mortality rate (18.8%). Model calibration was improved after applying first-level customisation (Ĉ = 6.39, P = 0.78) although discrimination was not affected.

    CONCLUSION: APACHE IV is not suitable for application in HSA ICU, without further customisation. The model's lack of fit in the Malaysian study is attributed to differences in the baseline characteristics between HSA ICU and APACHE IV datasets. Other possible factors could be due to differences in clinical practice, quality and services of health care systems between Malaysia and the United States.

    Matched MeSH terms: Hospital Mortality
  4. Heng DM, Lee J, Chew SK, Tan BY, Hughes K, Chia KS
    Ann Acad Med Singap, 2000 Mar;29(2):231-6.
    PMID: 10895345
    INTRODUCTION: This is the first prospective cohort study in Singapore to describe the incidence of ischaemic heart disease (IHD) and stroke among Chinese, Malays and Asian Indians.

    MATERIALS AND METHODS: The Singapore Cardiovascular Cohort Study is a longitudinal follow-up study on a general population cohort of 5920 persons drawn from 3 previous cross-sectional surveys. Morbidity and mortality from IHD and stroke were ascertained by record linkage using a unique identification number with the death registry, Singapore Myocardial Infarct Registry and in-patient discharge databases.

    RESULTS: There were 193 first IHD events and 97 first strokes during 52,806 person-years of observation. The overall incidence of IHD was 3.8/1000 person-years and that of stroke was 1.8/1000 person-years. In both males and females, Indians had the highest IHD incidence, followed by Malays and then Chinese. For males after adjusting for age, Indians were 2.78 times (95% CI 1.86, 4.17; P < 0.0001) and 2.28 times (95% CI 1.34, 3.88; P = 0.002) more likely to get IHD than Chinese and Malays respectively. For females after adjusting for age, Indians were 1.97 times (95% CI 1.07, 3.63; P = 0.03) and 1.37 times (95% CI 0.67, 2.80; P = 0.39) more likely to get IHD than Chinese and Malays respectively. For stroke, male Chinese and Indians had higher incidence than Malays (though not statistically significant). However, in females, Malays had the highest incidence of stroke, being 2.57 times (95% CI 1.31, 5.05; P = 0.008) more likely to get stroke than Chinese after adjustment for age.

    CONCLUSIONS: This prospective study of both mortality and morbidity has confirmed the higher risk of IHD in Indians. It has also found that Malay females have a higher incidence of stroke, which deserves further study because of its potential public health importance.

    Matched MeSH terms: Myocardial Ischemia/mortality; Stroke/mortality
  5. Sivanesaratnam V
    Ann Acad Med Singap, 1998 Sep;27(5):622-6.
    PMID: 9919328
    Although the primary operative mortality following radical hysterectomy for stage IB and early stage IIA cervical carcinoma is less than 1%, survival is poor in those patients with histological evidence of "risk" features--lymph node metastases, lymphatic vascular tumour permeation and clinically undetected parametrial metastases. In the 7-year period 1983 to 1989, 239 patients with stage IB and early IIA disease had radical hysterectomy and pelvic lymphadenectomy. One hundred and eight patients (45.2%) had various poor prognostic histological features and received adjuvant chemotherapy--70 had cisplatin, vinblastine, bleomycin (PVB), 16 had mitomycin C (MMC) and 22 others received mitomycin C + 5-fluorouracil (5-FU). Although not randomised, the risk factors present in each group were identical. These patients have now been followed up for periods ranging from 8 to 14 years. All recurrences, except one, occurred within 23 months of surgery; in the remaining this occurred 8 years later. This suggests that very close long-term follow-up is needed. Recurrences were markedly higher in the group who refused adjuvant chemotherapy (31.6%). The 10-year survival in patients without risk factors was 97.2%. In those patients with risk factors refusing adjuvant therapy it was 73.7%. The adjuvant chemotherapy group had a better survival of 86.1% (P = 0.001). The 10-year survivals in patients with positive nodes were similar--66.7% in the MMC group and 71.4% in the PVB group. The 10-year survival in patients with squamous cell carcinoma was significantly better (90.3%) in the mitomycin C (and MMC + 5-FU) group compared to the PVB group (80.1%) (P = 0.005). The 10-year survival in patients with adenocarcinoma and adenosquamous carcinoma was significantly better (96.3%) in the PVB group compared to those receiving MMC (and MMC + 5-FU) (57.1%) (P = 0.01). It would, thus, appear that the adjuvant chemotherapy of choice for patients with squamous cell carcinoma would be MMC (and MMC + 5-FU) and for those with adenocarcinoma, the PVB regime.
    Matched MeSH terms: Uterine Cervical Neoplasms/mortality
  6. Lun KC
    Ann Acad Med Singap, 1995 May;24(3):382-92.
    PMID: 7574420
    General life tables for the 1990 Singapore resident population are given in this paper. Analyses were carried out separately for males and females for all ethnic groups as well as for Chinese, Malays and Indians. Average fractions of the last age interval lived were used to give a more precise derivation of the life table death rates from their corresponding age-specific death rates. The results show that in 1990, Singapore males had achieved a life expectancy at birth of 73.7 years while the females had attained a level of 78.6 years. These levels were comparable to those of many developed countries. Other interesting features include higher differentials in the life expectancies between sexes among the Chinese and the Indians taking over the Malays for second placing in terms of life expectancy at birth for both sexes. As a result, the Indians registered a 12% gain in life expectancy at birth for males for the decade 1980 to 1990, compared to only 7.1% for Chinese and 4.4% for Malays as well as nearly 10% for females compared to only 6.2% for Chinese and 6.3% for Malays. A subsequent paper will highlight the results of multiple-decrement life table analyses which will summarise the mortality of the 1990 Singapore resident population for various component causes of death rather than for all causes combined.
    Matched MeSH terms: Mortality*
  7. Lin HP
    Ann Acad Med Singap, 1993 Mar;22(2):182-6.
    PMID: 8363329
    Significant advances in diagnosis and management have cured the majority of children with cancer. In the leukaemias, the commonest childhood malignancy, intensive induction-consolidation is important to ensure a lasting cure in about 65-80% and to eliminate the traditionally bad prognostic risk factors associated with less intensive treatment. Bone marrow transplantation (BMT) has a curative role in the minority who relapse particularly while on treatment. With few exceptions, most paediatric solid tumours are curable. Although the multimodal approach is responsible for the progress made, chemotherapy has emerged to play a dominant role. It has, in several tumours, obviated or reduced the need for radiotherapy and/or surgery. In Wilms' tumour and Hodgkin's disease, refinement of treatment is now in progress to reduce therapy-related morbidity while not sacrificing efficacy.
    Matched MeSH terms: Neoplasms/mortality
  8. Mustaffa BE
    Ann Acad Med Singap, 1985 Apr;14(2):272-6.
    PMID: 4037685
    Estimated prevalence of diabetes mellitus in Malaysia was about 2%. Diabetes was most common in Indians especially males and least common in Chinese. There was a slight male preponderance seen in Malays and Indians. Positive family history was obtained in 14% of cases most commonly in Malays, almost 1/3 of whom had more than one family member with diabetes. Familial association was uncommon in Chinese. Over 50% of patients were overweight. Obesity was noted in nearly 70% of female Malays and Indians while the majority of Chinese were not overweight. More than 80% of patients were non insulin requiring. Youth onset diabetes was considered rare; those 10 years and below were estimated to be only 0.4% and below 20 years of age between 2%-4% of the diabetic population. Females were twice as common than males in this type of diabetes and familial association was greater. Malnutrition-related diabetes and pancreatic calcification were not well-documented but youth-onset non insulin requiring diabetics with mild symptoms but strong family history of diabetes were observed. More than half of hospital-based patients had evidence of complications, mainly amongst Malays and Indians. Hypertension was the most frequent associated disease followed by foot ulcers and ischaemic heart disease. Hypertension usually associated with chronic renal failure was most common amongst Malays while gangrenic ulcers and heart diseases were seen mainly in Indians. The major causes of death were chronic renal failure, myocardial infarction, ketoacidosis, stroke and septicaemia related to gangrene.(ABSTRACT TRUNCATED AT 250 WORDS)
    Matched MeSH terms: Diabetes Mellitus/mortality
  9. Ng CS, Lim LS, Chng KP, Lim P, Cheah JS, Yeo PP, et al.
    Ann Acad Med Singap, 1985 Apr;14(2):297-302.
    PMID: 4037689
    225 women with diabetes in pregnancy were managed by a team of obstetricians, physicians (endocrinologists) and paediatricians from the National University of Singapore. A protocol of management was formulated and followed. The incidence of 1.1% or 1 in 90 pregnancies was found, with significantly higher incidence in Indians and lower in Malays. There were 37 established diabetics and 188 diagnosed during pregnancy. Of these (188), 74 were gestational diabetics. All the women were treated with Insulin and Diet or Diet alone. 177 (79%) were treated with Insulin and Diet. Blood sugar profiles were done for monitoring diabetic control. 72.8% of the women were between para 0 and 1 and 85.2% between the ages of 20 and 34. 72.5% of the women delivered at 38 weeks gestation or later. 48.9% went into spontaneous labour, 32.4% were induced and 18.7% had elective caesarean section. 62.2% of the women had labour of less than 12 hours. The overall caesarean section rate was 41.7%. There were 3 stillbirths and 2 neonatal deaths. The perinatal mortality rate was 2.2%. Thirteen babies had congenital malformations (5.8%). 77.8% of the babies had Apgar score of 7 or more at 5 minutes after delivery. 79.1% of the babies weighed between 2.5 kgm and 3.9 kgm. Pre-eclamptic toxaemia was the commonest complication in pregnancy followed by Urinary Tract Infection and Polyhydramnios. Postpartum complications in the mother were confined to 14 women (6.2%), and wound infection or breakdown was the commonest cause.
    Matched MeSH terms: Infant Mortality
  10. Saw HS, Chong KT, Singham AM
    Ann Acad Med Singap, 1981 Oct;10(4 Suppl):93-8.
    PMID: 7344608
    Updated data on permanent cardiac pacing in Malaysia is presented. Over the past 3 1/2 years (1976-1980), 75 patients underwent insertion of pacemakers giving an annual incidence of about 20 cases as compared with a total of 21 cases in the previous 8 years (1968-1977). Many of the features reported in an earlier paper in 1977 viz mode of presentation, age and sex distribution and indications for pacing remain unchanged. Over this period only 4 patients required lead replacement. Since concentrating mainly on the use of epicardial leads implanted via a subxiphoid approach, complications have been remarkably low. The problem of availability of pacemakers has been averted. Cost remains a major consideration when recommending one pacemaker in preference over another. The details concerning clinical features, indications for pacing, complications and other problems encountered in the management of these patients are discussed.
    Matched MeSH terms: Heart Diseases/mortality
  11. Goh KT
    Ann Acad Med Singap, 1980 Apr;9(2):136-41.
    PMID: 6775577
    257 cases of acute hepatitis B were reported between January 1977 and June 1979. This constituted about one-third of all reported acute viral hepatitis cases in Singapore. The mean annual morbidity and mortality rates per 100,000 was 4.4 and 0.12 respectively. The case-fatality rate was 2.7%. The age-specific morbidity rates were high in the 15-24 and 25-34 years age groups, while the ethnic specific morbidity rate was highest in Indians. The male to female ratio was 4.6: 1. Cases were concentrated in urban and suburban areas with high population density. Three outbreaks, one traced to contaminated needles and syringes, one to contaminated tattoo neeedles, and amongst close contacts, were described. Although parenteral procedures were associated with hepatitis B infection (p < 0.005), non-parenteral or inapparent parenteral mode of transmission probably contributes to a significant extent in the transmission of hepatitis B in Singapore. Studies to determine the role of perinatal transmission, and of vectors, in maintaining the endemicity of the disease, were suggested.
    Matched MeSH terms: Hepatitis B/mortality
  12. Suleiman AB, Morad Z, Tong CT
    Ann Acad Med Singap, 1987 Jan;16(1):175-8.
    PMID: 3496037
    In a review of 112 patients with SLE nephritis treated between 1976 and 1982, 31 were known to have died. Renal failure (32.2%) was the commonest cause of death. Gastrointestinal haemorrhage (16%), infections (12.8%) and central nervous system involvement (6.5%) were important causes of death. Thirteen out of 17 patients dying in the presence of renal failure had initially presented with renal impairment. Renal biopsies in 16 patients who have died showed diffuse proliferative glomerulonephritis in all except 1 patient, and uraemia was the commonest cause of death in these patients. Pregnancies terminating in abortions were followed by complications in 5 patients. Discontinuation of steroid therapy by patients was followed by complications, and ended in death in 6 patients.
    Matched MeSH terms: Gastrointestinal Hemorrhage/mortality; Lupus Nephritis/mortality*; Uremia/mortality
  13. Tan KL
    Ann Acad Med Singap, 1984 Apr;13(2):252-63.
    PMID: 6497323
    Perinatal mortality rates have been gradually declining in all countries. The initial decline mainly resulted from improvements in the late foetal mortality rates. Later with improvements in neonatal care, early neonatal mortality rates also improved. The developed countries have consistently shown better results than the developing countries, an indication of the higher standard of living, general health as well as the delivery of health care in these countries. In the Singapore situation, a rapid improvement in perinatal mortality was initially observed due to improvements in the late foetal mortality, followed later by reduction in the early neonatal mortality due to upgrading of neonatal intensive care. The perinatal mortality rate is lowest in the Chinese compared to the Indians and Malays, most likely due to the dietary practices of the three ethnic groups in Singapore; while the Chinese encourage extra nutrition in the pregnant female, the Malays and Indians tend to practise dietary restriction during this period. The improved nutrition of the pregnant mother is a factor in improving the perinatal mortality.
    Matched MeSH terms: Infant Mortality*
  14. Hughes K, Yeo PP, Lun KC, Sothy SP, Thai AC, Wang KW, et al.
    Ann Acad Med Singap, 1989 May;18(3):245-9.
    PMID: 2774470
    Mortality from ischaemic heart disease in Singapore is now reaching comparability with the West. For the early 1980s, rates for Indians and Malays were higher than in U.S.A. and England and Wales and while those for Chinese were lower they were considerably higher than in Japan. In keeping with this the levels of the major risk factors in Singapore are now comparable to the West. Cigarette smoking in males is virtually the same as in Britain, while the proportion of hypertensives on medication is higher than in the West. The main cause for concern is the current high levels of serum cholesterol in Singapore and strenuous health education efforts are needed to bring about dietary changes.
    Matched MeSH terms: Coronary Disease/mortality*
  15. Lyn PC
    Ann Acad Med Singap, 1987 Apr;16(2):310-2.
    PMID: 3318659
    Of the seventy cases of cerebral malaria seen at the Duchess of Kent Hospital, Sandakan between January 1984 and June 1986, 57 (81.4%) were due to plasmodia falciparum and 13 (18.6%) were due to mixed p. vivax--p. falciparum infections. Mixed infection cerebral malaria was associated with a more severe anaemia and may carry a poorer prognosis. Indigenous children under five years of age are particularly at risk of death from mixed infections.
    Matched MeSH terms: Brain Diseases/mortality*; Malaria/mortality*
  16. Hughes K
    Ann Acad Med Singap, 1989 Nov;18(6):642-5.
    PMID: 2624412
    Age-standardised death rates, for ages 35-64 years in both sexes, from ischaemic heart disease, cerebrovascular disease, and hypertensive disease for Chinese, Malays, and Indians in Singapore (1980-84) have been compared with those in England and Wales, USA and Japan (1982). For ischaemic heart disease Indians have the highest mortality, then Malays, with Chinese less than the Western countries but more than Japan. For cerebrovascular disease the Malays have highest mortality, then Indians, then Chinese, followed by Japan, England and Wales, and USA in that order. For hypertensive disease it is again Malays, then Indians, then Chinese, but followed by the different order of USA, England and Wales, and Japan. The differences are discussed in the light of declining trends in mortality from these disease in Singapore over the preceding 25 years. The special problems of ischaemic heart disease in Indians and hypertension and it's sequelae in Malays are highlighted.
    Matched MeSH terms: Cardiovascular Diseases/mortality*; Cerebrovascular Disorders/mortality*
  17. Choo KE, Wan Ariffin WA, Chua SP
    Ann Acad Med Singap, 1988 Jul;17(3):438-42.
    PMID: 3218934
    A retrospective study of 84 cases of neonatal septicaemia admitted into a neonatal unit in a rural area of Malaysia for 1 year between 1st September 1985 to 31st August 1986 was carried out to determine the spectrum of micro-organisms and predisposing factors in relation to early and late onset septicaemia. The incidence of neonatal septicaemia was 2.13 per 1,000 live-births per year and the case fatality was 41.7% with higher case fatality in those who were premature, those who presented as early onset and those who had gram negative septicaemia. The mean age of onset of septicaemia was 7.8 days (range from 2 hours to 27 days). Forty four (52%) neonates had early onset septicaemia with mean age of onset at 2.7 days; forty (48%) neonates had late onset septicaemia presenting at 13.6 days of life. Gram negative organisms such as Klebsiella, Pseudomonas, sp., E. coli and Streptococcus, especially group B Streptococcus were the major organisms in the early onset septicaemia. Staphylococcus aureus and Staphylococcus epidermidis were the major organisms responsible for the late onset septicaemia. Obstetrical factors played an important role in early onset septicaemia. Prematurity was the most common predisposing factor. Invasive diagnostic and therapeutic procedures including surgery highlighted once again the importance of these procedures in predisposing the newborn to infection.
    Matched MeSH terms: Infant, Premature, Diseases/mortality; Sepsis/mortality
  18. Suleiman AB
    Ann Acad Med Singap, 1982 Jan;11(1):32-5.
    PMID: 7073225
    Over a five year period, 184 patients were treated for acute renal failure. Uraemia was usually treated by peritoneal dialysis, and haemodialysis was reserved for post surgical and hypercatabolic patients. The overall mortality was 33.2% and was highest among surgical patients. These results were similar to previous reports. Peritoneal dialysis was usually effective in controlling uraemia. Uncontrolled sepsis remains a major problem, and septicaemia and gastrointestinal bleeding were adverse factors affecting the outcome. The combination of septicaemia and gastrointestinal bleeding commonly led to a fatal outcome.
    Matched MeSH terms: Acute Kidney Injury/mortality
  19. Lee WS, Puthucheary SD, Parasakthi N
    Ann Trop Paediatr, 2000 Jun;20(2):125-9.
    PMID: 10945063
    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.
    Matched MeSH terms: Salmonella Infections/mortality
  20. Abdul-Aziz MH, Abd Rahman AN, Mat-Nor MB, Sulaiman H, Wallis SC, Lipman J, et al.
    Antimicrob Agents Chemother, 2016 01;60(1):206-14.
    PMID: 26482304 DOI: 10.1128/AAC.01543-15
    Doripenem has been recently introduced in Malaysia and is used for severe infections in the intensive care unit. However, limited data currently exist to guide optimal dosing in this scenario. We aimed to describe the population pharmacokinetics of doripenem in Malaysian critically ill patients with sepsis and use Monte Carlo dosing simulations to develop clinically relevant dosing guidelines for these patients. In this pharmacokinetic study, 12 critically ill adult patients with sepsis receiving 500 mg of doripenem every 8 h as a 1-hour infusion were enrolled. Serial blood samples were collected on 2 different days, and population pharmacokinetic analysis was performed using a nonlinear mixed-effects modeling approach. A two-compartment linear model with between-subject and between-occasion variability on clearance was adequate in describing the data. The typical volume of distribution and clearance of doripenem in this cohort were 0.47 liters/kg and 0.14 liters/kg/h, respectively. Doripenem clearance was significantly influenced by patients' creatinine clearance (CL(CR)), such that a 30-ml/min increase in the estimated CL(CR) would increase doripenem CL by 52%. Monte Carlo dosing simulations suggested that, for pathogens with a MIC of 8 mg/liter, a dose of 1,000 mg every 8 h as a 4-h infusion is optimal for patients with a CL(CR) of 30 to 100 ml/min, while a dose of 2,000 mg every 8 h as a 4-h infusion is best for patients manifesting a CL(CR) of >100 ml/min. Findings from this study suggest that, for doripenem usage in Malaysian critically ill patients, an alternative dosing approach may be meritorious, particularly when multidrug resistance pathogens are involved.
    Matched MeSH terms: Gram-Negative Bacterial Infections/mortality; Sepsis/mortality
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