[show abstract][hide abstract] ABSTRACT: The appropriate selection of empirical antibiotics based on the pattern of local antibiotic resistance can reduce the mortality rate and increase the rational use of antibiotics.
We analyze the pattern of antibiotic use and the sensitivity patterns of antibiotics to support the rational use of antibiotics in patients with sepsis.
A retrospective observational study was conducted in adult sepsis patient at one of Indonesian hospital during January-December 2011. Data were collected from the hospital medical record department. Descriptive analysis was used in the processing and interpretation of data.
A total of 76 patients were included as research subjects. Lung infection was the highest source of infection. In the 66.3% of clinical specimens that were culture positive for microbes, Klebsiella pneumoniae, Escherichia coli, Staphylococcus hominis were detected with the highest frequency. The six most frequently used antibiotics, levofloxacin, ceftazidime, ciprofloxacin, cefotaxime, ceftriaxone, and erythromycin, showed an average resistance above 50%.
The high use of antibiotic with a high level resistance requires a policy to support its rational use. Local microbial pattern based on site infection and pattern of antibiotics sensitivity test can be used as supporting data to optimize appropriateness of empirical antibiotics therapy in sepsis patients.
North American journal of medical sciences. 06/2013; 5(6):344-52.
[show abstract][hide abstract] ABSTRACT: As dengue fever is undifferentiated from other febrile illnesses in the tropics and the clinical course is unpredictable, early diagnosis is important. Several commercial assays to detect dengue NS1 antigen have been developed; however, their performances vary and data is lacking from hyper-endemic areas where all four serotypes of dengue are equally represented. To assess the sensitivity of the Bio-Rad platelia Dengue NS1 antigen assay according to virus serotype, immune status, gender, and parameters of severe disease, acute sera from 220 individuals with confirmed dengue and 55 individuals with a non-dengue febrile illness were tested using the Bio-Rad platelia Dengue NS1 antigen assay. The overall sensitivity of the NS1 ELISA was 46.8% and the specificity was 100%. The sensitivity in primary infections was significantly higher than in secondary infections (100% vs. 35.7%). In secondary infections, the sensitivity of NS1 detection was highest in DENV-3 (47.1%), followed by DENV-1 (40.9%), DENV-2 (30%) and DENV-4 (27%) infections. NS1 was less frequently detected in sera with high titers of HI antibodies or in acute samples from patients whose pre-illness sera showed neutralizing antibodies to more than one serotype. The detection of NS1 was higher in females, severe cases, and individuals with lower platelet counts (<100,000/mm(3)). While the overall sensitivity of this NS1 ELISA is poor, our data suggest that in secondary infections, detection may be predictive of a more severe illness.
PLoS ONE 01/2013; 8(11):e80891. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: HIV-associated subacute meningitis is mostly caused by tuberculosis or cryptococcosis, but often no etiology can be established. In the absence of CT or MRI of the brain, toxoplasmosis is generally not considered as part of the differential diagnosis.
We performed cerebrospinal fluid real time PCR and serological testing for Toxoplasma gondii in archived samples from a well-characterized cohort of 64 HIV-infected patients presenting with subacute meningitis in a referral hospital in Indonesia. Neuroradiology was only available for 6 patients. At time of presentation, patients mostly had newly diagnosed and advanced HIV infection (median CD4 count 22 cells/mL), with only 17.2% taking ART, and 9.4% PJP-prophylaxis. CSF PCR for T. Gondii was positive in 21 patients (32.8%). Circulating toxoplasma IgG was present in 77.2% of patients tested, including all in whom the PCR of CSF was positive for T. Gondii. Clinically, in the absence of neuroradiology, toxoplasmosis was difficult to distinguish from tuberculosis or cryptococcal meningitis, although CSF abnormalities were less pronounced. Mortality among patients with a positive CSF T. Gondii PCR was 81%, 2.16-fold higher (95% CI 1.04-4.47) compared to those with a negative PCR.
Toxoplasmosis should be considered in HIV-infected patients with clinically suspected subacute meningitis in settings where neuroradiology is not available.
[show abstract][hide abstract] ABSTRACT: Fluorescence microscopy (FM) has not been implemented widely in TB endemic settings and little evaluation has been done in HIV-infected patients. We evaluated diagnostic performance, time and costs of FM with light-emitting diodes technology (LED-FM), compared with conventional (Zieh-Neelsen) microscopy in a hospital in Indonesia which acts as referral centre for HIV-infected patients.
We included pulmonary tuberculosis suspects from the outpatient and HIV clinic. Direct and concentrated sputum smears were examined using LED-FM and ZN microscopy by two technicians who were blinded for the HIV-status and the result of the comparative test. Mean reading time per slide was recorded and cost of each slide was calculated. Mycobacteria culture served as the reference standard.
Among 404 tuberculosis suspects from the outpatient clinic and 256 from the HIV clinic, mycobacteria culture was positive in 12.6% and 27%, respectively. The optimal sensitivity of LED-FM was achieved by using a threshold of ≥2 AFB/length. LED-FM had a higher sensitivity (75.5% vs. 54.9%, P<0.01) but lower specificity (90.0% vs 96.6%, P<0.01) compared to ZN microscopy. HIV was associated with a lower sensitivity but similar specificity. The average reading time using LED-FM was significantly shorter (2.23±0.78 vs 5.82±1.60 minutes, P<0.01), while costs per slide were similar.
High sensitivity of LED-FM combined with shorter reading time of sputum smear slides make this method a potential alternative to ZN microscopy. Additional data on specificity are needed for effective implementation of this technique in high burden TB laboratories.
PLoS ONE 01/2013; 8(4):e61727. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: Bacteriological confirmation of tuberculous (TB) meningitis is difficult. Culture is slow and microscopy has insufficient sensitivity. We evaluated real time PCR targeting insertion sequence IS6110 among 230 consecutive adult patients with subacute meningitis in a referral hospital in Indonesia.
Cerebrospinal fluid (CSF) samples were examined using microscopy, solid and liquid culture, and real time IS6110-PCR with a fluorescence-labeled probe using DNA extracted from CSF. CSF samples from 40 non-infectious neurology patients were used as negative controls. IS6110-PCR results were linked with clinical and CSF characteristics.
Most patients presented with subacute meningitis, after a median of 14 days of symptoms (range 7-30). After exclusion of cryptococcal and bacterial meningitis, 207 patients were classified as definite or probable TB meningitis; 17.9% with HIV infection. Among this group IS6110-PCR gave the highest positivity rate (68%, 95% CI 62-74%) compared with microscopy of ZN-stained slides (11%, 95% CI 7-15%), and mycobacterial culture using solid (36%, 95% CI 29-42%) and liquid (44%, 95% CI 37-51%) media. IS6110-PCR was positive in 92% of patients with culture-positive and 42% of patients with culture-negative probable TB meningitis. Among culture-negative patients, a positive PCR was associated with a history of TB treatment, a longer duration of illness, a higher CSF cell count and protein, and a lower CSF glucose. IS6110-PCR was negative in all CSF samples from non-meningitis control patients.
Real time IS6110-PCR is a quick, sensitive, and specific test for diagnosing of TB meningitis in this setting. Its performance in other (less-developed) settings needs further study.
PLoS ONE 01/2012; 7(12):e52001. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: Recent data suggest that autophagy is important for intracellular killing of Mycobacterium tuberculosis, and polymorphisms in the autophagy gene IRGM have been linked with susceptibility to tuberculosis (TB) among African-Americans, and with TB caused by particular M. tuberculosis genotypes in Ghana. We compared 22 polymorphisms of 14 autophagy genes between 1022 Indonesian TB patients and 952 matched controls, and between patients infected with different M. tuberculosis genotypes, as determined by spoligotyping. The same autophagy polymorphisms were studied in correlation with ex-vivo production of TNF, IL-1β, IL-6, IL-8, IFN-γ and IL-17 in healthy volunteers. No association was found between TB and polymorphisms in the genes ATG10, ATG16L2, ATG2B, ATG5, ATG9B, IRGM, LAMP1, LAMP3, P2RX7, WIPI1, MTOR and ATG4C. Associations were found between polymorphisms in LAMP1 (p = 0.02) and MTOR (p = 0.02) and infection with the successful M. tuberculosis Beijing genotype. The polymorphisms examined were not associated with M. tuberculosis induced cytokines, except for a polymorphism in ATG10, which was linked with IL-8 production (p = 0.04). All associations found lost statistical significance after correction for multiple testing. This first examination of a broad set of polymorphisms in autophagy genes fails to show a clear association with TB, with M. tuberculosis Beijing genotype infection or with ex-vivo pro-inflammatory cytokine production.
PLoS ONE 01/2012; 7(8):e41618. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: Five Mycobacterium tuberculosis isolates were obtained from three body sites from a Dutch patient. The isolates displayed a single genotype by 24-locus MIRU-VNTR typing (except for a single locus not amplified from one isolate) but were differentiated by small variations in IS6110 fingerprints, spoligotypes, 6 hypervariable MIRU-VNTR loci, and/or DiversiLab profiles, revealing patterns of microevolution in a clonal infection.
Journal of clinical microbiology 10/2010; 48(10):3813-6. · 4.16 Impact Factor
[show abstract][hide abstract] ABSTRACT: Animal studies have shown that the globally emerging Beijing genotype strains of Mycobacterium tuberculosis are more virulent than other strains. We examined whether Beijing strains increase treatment failure in a prospective cohort study in Indonesia. Among 818 tuberculosis cases, positive sputum culture results after 6 months of treatment were more common among patients infected with Beijing strains (33.4%) than among those infected with non-Beijing strains (relative risk, 1.94 [95% confidence interval, 1.26-3.00]), even after adjustment for differences in drug resistance. These data suggest that M. tuberculosis Beijing genotype strains have a higher capacity to withstand tuberculosis treatment, even in the absence of drug resistance.
The Journal of Infectious Diseases 02/2010; 201(4):553-7. · 5.85 Impact Factor
[show abstract][hide abstract] ABSTRACT: The wide geographic distribution of one clade of Mycobacterium tuberculosis, the Beijing genotype family, and its genetic homogeneity, suggests that strains belonging to this grouping might have a selective advantage over other M tuberculosis strains. This hypothesis was addressed by reviewing molecular-epidemiological, experimental, and clinical studies. Beijing strains represent about 50% of strains in east Asia and at least 13% of strains worldwide. Their emergence might be linked to escape from BCG vaccination, and to multidrug resistance, which is associated with the Beijing genotype in many areas. Different animal models have shown Beijing strains to be more virulent, and to cause more histopathological changes, higher outgrowth, and increased mortality. At a molecular level, Beijing strains have specific properties in terms of protein and lipid structures and their interaction with the human immune system. Finally, the Beijing genotype has been linked to polymorphisms in immune genes, suggesting the possibility of human-mycobacterial co-evolution. The emergence of the Beijing genotype family might represent an evolutionary response of M tuberculosis to vaccination or antibiotic treatment, with an important negative impact on tuberculosis control. More research is needed to further unravel the mechanisms underlying the emergence of M tuberculosis Beijing genotype strains, and examine the implications for future control strategies.
The Lancet Infectious Diseases 02/2010; 10(2):103-11. · 19.97 Impact Factor
[show abstract][hide abstract] ABSTRACT: Differences in host immune genes may predispose to tuberculosis caused by particular Mycobacterium tuberculosis genotypes. We examined this hypothesis in Indonesia by spoligotyping M. tuberculosis isolates recovered from 336 patients with pulmonary tuberculosis and typing the patients' SLC11A1 gene (formerly known as "NRAMP1"), which is involved in susceptibility to tuberculosis. The M. tuberculosis Beijing genotype, which comprised 29.8% of all isolates, was strongly associated with 2 polymorphisms in SLC11A1: the D543N G allele (odds ratio [OR], 2.15; P=.005) and the 3' untranslated region (3'UTR) insertion/insertion genotype (OR, 2.5; P=.001). This finding supports the hypothesis of coevolution of M. tuberculosis and the human immune system.
The Journal of Infectious Diseases 12/2009; 200(11):1671-4. · 5.85 Impact Factor
[show abstract][hide abstract] ABSTRACT: Indonesia has a concentrated but rapidly growing HIV epidemic. We examined the effect of HIV on causative organisms, clinical features and prognosis of adult meningitis.
A prospective cohort study.
All adult patients at a referral hospital who underwent cerebrospinal fluid examination for suspected meningitis were examined for HIV and included in a prospective cohort study. Microbiological testing was done for common bacterial pathogens, mycobacteria and fungi. Patients were followed for at least 6 months, and logistic regression models were used to identify risk factors for mortality.
Among 185 patients who mostly presented with subacute meningitis, 60% were male and the median age was 30 years. HIV infection was present in 25% of the patients; almost two-thirds were newly confirmed, and all presented with severe immunosuppression (median CD4 cell count 13/microl, range 2-98). One-third of HIV-infected patients had cryptococcal meningitis whereas two-thirds suffered from tuberculosis. After 1 month, 41% of patients had died. HIV infection was strongly associated with 1-month mortality (adjusted odds ratio 12.15; 95% confidence interval 3.04-15.72) and death during extended follow-up (hazard ratio 2.48; 95% confidence interval 1.97-5.74).
Although HIV is still uncommon in the general population in Indonesia, its prevalence among adult meningitis cases already seems high. Mycobacterium tuberculosis and Cryptococcus neoformans are the main causes of meningitis in this setting, and mortality is very high, especially in HIV-infected patients. Our data suggest that adult meningitis cases in Indonesia should be screened routinely for HIV infection. Further studies are needed to address the high mortality.
AIDS (London, England) 09/2009; 23(17):2309-16. · 4.91 Impact Factor
[show abstract][hide abstract] ABSTRACT: to examine among high-risk populations or patients with signs or symptoms suggesting HIV-infection, two tests or even one single test might be sufficiently accurate for diagnosis of HIV in a hospital setting in Indonesia.
we retrospectively examined the rate of false-positive results of initial HIV-tests for all subjects tested in the referral hospital for HIV in West-Java, Indonesia, between 2006 and 2008. We also calculated the positive and negative predictive value of single test results and dual-testing, based on sensitivity and specificity of commonly used methods and prevalence data from Indonesia.
among 3121 subjects, 803 were tested positive (25.7%). The initial rapid HIV-tests did not show a single false positive result, and no discrepancy was found between the second and third supplemental tests. Based on their high accuracy, most rapid tests carry a low risk of false-positive results among risk groups. Dual testing algorithms almost eliminate the risk of false-positive HIV-results, and are probably as accurate as three tests, even in low prevalence settings.
based on expected prevalence rates and the accuracy of methods used in Indonesia, one or two tests are usually accurate for HIV-diagnosis, especially for high risk populations. The possible implications and optimal conditions for more simple testing algorithms warrant further investigation.
[show abstract][hide abstract] ABSTRACT: To investigate the hematologic manifestation and the relationship of the abnormalities with mortality.
We examined hematologic data from 10 Avian influenza patients in Hasan Sadikin Hospital Bandung between November 2005 and March 2007.
The mortality rate was 70%. Anemia was found in 30% (3 of 10 patients). Leukopenia was found in 60% (6 of 10 patients. Lymphopenia and neutropenia were found in 50% (4 of 8 patients) and 62.5% (5 of 8 patients). Sixty percent (6 of 10 patients) had thrombocytopenia. Anemia was not correlated with mortality (OR=0.08). Leukopenia, neutropenia and lymphopenia were correlated with mortality (OR=5, OR=8 and OR=12, respectively). Thrombocytopenia was also correlated with mortality (OR=5).
Leukopenia, neutropenia, lymphopenia and thrombocytopenia were common findings among avian influenza patients in Hasan Sadikin Hospital. Decreased white blood cells and platelets were correlated with mortality.
[show abstract][hide abstract] ABSTRACT: HIV infection hampers diagnosis of pulmonary tuberculosis (PTB) because many pathogens cause pulmonary infection in HIV people and the load of Mycobacterium tuberculosis is lower in HIV patients. We conducted a literature review and prospectively examined clinical, radiological, and laboratory diagnosis of PTB in 71 HIV-patients (29 inpatients and 42 outpatients) in a teaching hospital in West Java, Indonesia. For both in- and outpatients, signs and symptoms were sensitive but not specific for PTB. Chest X-ray (CXR) was sensitive but less specific. Among hospitalized PTB suspects, 28,8% could not expectorate sputum. Compared to culture, ZN had a sensitivity of 11.1% and 66.7% for in- and outpatients, respectively. From the literature, fluorescence microscopy, liquid culture, and nucleic acid assays can improve diagnosis of PTB in HIV, while IFNg-release assays lack sensitivity, especially in advanced HIV. The current practice of using CXR and microscopy lacks sensitivity for diagnosing PTB in HIV patients. Sputum culture is more sensitive but slow. Fluorescence microscopy might be a quick, relatively sensitive and feasible option in Indonesia. However, because of the frequent absence of sputum, especially in patients with advanced HIV-AIDS patients, there is an urgent need for alternative diagnostic methods using blood or urine.
[show abstract][hide abstract] ABSTRACT: Comparison of Mycobacterium tuberculosis genotype distributions in different areas might help to find determinants of the emergence of certain genotypes, such as the Beijing family. In this study, M. tuberculosis isolates originating from patients from two Indonesian islands were genotyped, and possible associations with patients' characteristics and drug resistance were explored. A high degree of genetic diversity was observed among the M. tuberculosis strains, and a significant difference was found in the geographical distribution of genotype families. The predominant Beijing genotype family was isolated from 268 of 813 patients from West Java (33.0%) versus 12 of 84 patients from Timor (14.3%) (P = 0.002). Family F (East African-Indian) (33.3%) and family D (Latin American and Mediterranean) (20.0%) were more prevalent in Timor. No significant associations were found between genotype families and age, vaccination with Mycobacterium bovis BCG, previous treatment, disease localization, or drug resistance. Possible explanations for the differences in the geographical distribution of the M. tuberculosis genotypes are discussed.
Journal of clinical microbiology 11/2008; 46(11):3639-45. · 4.16 Impact Factor
[show abstract][hide abstract] ABSTRACT: Diabetes mellitus (DM) is a known risk factor for tuberculosis (TB), and with the increasing prevalence of type 2 DM in less developed regions, many patients with TB will have concomitant DM. Presently, little is known about the effect of DM on the clinical presentation and treatment outcome of TB.
In an urban setting in Indonesia, 737 patients with pulmonary TB were screened for DM and were followed up prospectively during TB treatment. Clinical characteristics and outcome were compared between patients with TB who had DM and patients with TB who did not have DM.
DM was diagnosed in 14.8% of patients with TB and was associated with older age and a greater body weight. On presentation, diabetic patients with TB had more symptoms but had no evidence of more-severe TB. After 2 months, results of sputum microscopic examination was more often positive in diabetic patients (18.1% vs. 10.0%). After 6 months, 22.2% of cultured sputum specimens from diabetic patients were positive for Mycobacterium tuberculosis (adjusted odds ratio, 7.65; P=.004).
DM seems to have a negative effect on the outcome of TB treatment. The underlying mechanisms for the different response to treatment in diabetic patients with TB must be explored. Screening for DM and subsequent glycemic control may improve the outcome of TB treatment.
[show abstract][hide abstract] ABSTRACT: Rifampin is a key drug for tuberculosis (TB) treatment. The available data suggest that the currently applied 10-mg/kg of body weight dose of rifampin may be too low and that increasing the dose may shorten the treatment duration. A double-blind randomized phase II clinical trial was performed to investigate the effect of a higher dose of rifampin in terms of pharmacokinetics and tolerability. Fifty newly diagnosed adult Indonesian TB patients were randomized to receive a standard (450-mg, i.e., 10-mg/kg in Indonesian patients) or higher (600-mg) dose of rifampin in addition to other TB drugs. A full pharmacokinetic curve for rifampin, pyrazinamide, and ethambutol was recorded after 6 weeks of daily TB treatment. Tolerability was assessed during the 6-month treatment period. The geometric means of exposure to rifampin (area under the concentration-time curve from 0 to 24 h [AUC(0-24)]) were increased by 65% (P < 0.001) in the higher-dose group (79.7 mg.h/liter) compared to the standard-dose group (48.5 mg.h/liter). Maximum rifampin concentrations (C(max)) were 15.6 mg/liter versus 10.5 mg/liter (49% increase; P < 0.001). The percentage of patients for whom the rifampin C(max) was > or =8 mg/liter was 96% versus 79% (P = 0.094). The pharmacokinetics of pyrazinamide and ethambutol were similar in both groups. Mild (grade 1 or 2) hepatotoxicity was more common in the higher-dose group (46 versus 20%; P = 0.054), but no patient developed severe hepatotoxicity. Increasing the rifampin dose was associated with a more than dose-proportional increase in the mean AUC(0-24) and C(max) of rifampin without affecting the incidence of serious adverse effects. Follow-up studies are warranted to assess whether high-dose rifampin may enable shortening of TB treatment.
Antimicrobial Agents and Chemotherapy 07/2007; 51(7):2546-51. · 4.57 Impact Factor
[show abstract][hide abstract] ABSTRACT: The Direct Repeat locus of the Mycobacterium tuberculosis complex (MTC) is a member of the CRISPR (Clustered regularly interspaced short palindromic repeats) sequences family. Spoligotyping is the widely used PCR-based reverse-hybridization blotting technique that assays the genetic diversity of this locus and is useful both for clinical laboratory, molecular epidemiology, evolutionary and population genetics. It is easy, robust, cheap, and produces highly diverse portable numerical results, as the result of the combination of (1) Unique Events Polymorphism (UEP) (2) Insertion-Sequence-mediated genetic recombination. Genetic convergence, although rare, was also previously demonstrated. Three previous international spoligotype databases had partly revealed the global and local geographical structures of MTC bacilli populations, however, there was a need for the release of a new, more representative and extended, international spoligotyping database.
The fourth international spoligotyping database, SpolDB4, describes 1939 shared-types (STs) representative of a total of 39,295 strains from 122 countries, which are tentatively classified into 62 clades/lineages using a mixed expert-based and bioinformatical approach. The SpolDB4 update adds 26 new potentially phylogeographically-specific MTC genotype families. It provides a clearer picture of the current MTC genomes diversity as well as on the relationships between the genetic attributes investigated (spoligotypes) and the infra-species classification and evolutionary history of the species. Indeed, an independent Naïve-Bayes mixture-model analysis has validated main of the previous supervised SpolDB3 classification results, confirming the usefulness of both supervised and unsupervised models as an approach to understand MTC population structure. Updated results on the epidemiological status of spoligotypes, as well as genetic prevalence maps on six main lineages are also shown. Our results suggests the existence of fine geographical genetic clines within MTC populations, that could mirror the passed and present Homo sapiens sapiens demographical and mycobacterial co-evolutionary history whose structure could be further reconstructed and modelled, thereby providing a large-scale conceptual framework of the global TB Epidemiologic Network.
Our results broaden the knowledge of the global phylogeography of the MTC complex. SpolDB4 should be a very useful tool to better define the identity of a given MTC clinical isolate, and to better analyze the links between its current spreading and previous evolutionary history. The building and mining of extended MTC polymorphic genetic databases is in progress.