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Epidemiology of Bloodstream Infections and Predictive Factors Of Jpn. J. Infect. Dis., 65, 28-32, 2012 Original Article Epidemiology of Bloodstream Infections and Predictive Factors of Mortality among HIV-Infected Adult Patients in Thailand in the Era of Highly Active Antiretroviral Therapy Sasisopin Kiertiburanakul1*, Siripen Watcharatipagorn1, Piriyaporn Chongtrakool2, and Pitak Santanirand2 1Department of Medicine and 2Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand (Received June 10, 2011. Accepted October 31, 2011) SUMMARY: Few studies have described the pattern of bloodstream infections (BSI) among HIV-in- fected patients in the highly active antiretroviral therapy (HAART) era, particularly in resource-limited settings. A retrospective cohort study was conducted among 140 HIV-infected patients who had a posi- tive blood culture from 2004–2008. Of the 140 patients, 91 (65z)weremalewithamean(SD)ageof38 (9.1) years and a median (IQR) CD4 cell count of 32 (9–112) cells/mm3. Community-acquired infection was detected in 89z of patients. The blood cultures contained Gram-negative bacteria, 40z; fungi, 24z; Mycobacterium spp., 20z; and Gram-positive bacteria, 16z. Common causative pathogens were Cryptococcus neoformans,21z; Salmonella spp., 15z;andMycobacterium tuberculosis,12z. Common focal sites of infection were the central nervous system, 24z; respiratory tract, 20z;andgas- trointestinal tract, 18z. CD4 cell count (OR, 0.61 per 50 cells/mm3 increment; 95z CI, 0.39–0.96; P ＝ 0.031) was the only factor associated with mycobacterial or fungal BSI. The crude mortality was 21z. HAART (OR, 0.23; 95z CI, 0.01–0.77; P ＝ 0.017), focal infection (OR, 0.31; 95z CI, 0.10–0.97; P ＝ 0.044), and complication (e.g., shock) (OR, 9.26; 95z CI, 3.25–26.42; P º 0.001) were the predic- tive factors of mortality. In conclusion, opportunistic infections are still the leading causes of BSI among HIV-infected patients in the HAART era. (ICU) admission rate (12). Another recent prospective INTRODUCTION study in Spain showed that BSI in HIV-infected patients Thailand began producing generic antiretroviral were often caused by Gram-positive pathogens (13,14). drugs in 2002 (1). Since then, the Thai government has Epidemiology of BSI in HIV-infected patients may supported the free provision of antiretroviral drugs to differ across geographic areas, and may depend on the human immunodeficiency virus (HIV)-infected patients availability of HAART in that region. HAART has led whoareenrolledintheuniversalcoveragehealthpro- to a significantly reduced incidence of bacteremia and a gram. Highly active antiretroviral therapy (HAART) modification of its characteristics (14). Studies on BSI has significantly improved prognosis and prolonged in HIV-infected patients before (9) and after (11) the AIDS-free survival worldwide (2–5). However, more widespread use of HAART in resource-limited settings than half of newly diagnosed Thai HIV-infected have been reported. However, there are few studies pub- patients have advanced HIV disease and are unaware of lished in English that surveyed BSI among HIV infec- their HIV status (6). Morbidity and mortality in HIV-in- ted-patients in Thailand, and some of these were con- fected patients is due to opportunistic infections caused ducted prior to the HAART era (15,16). One study by various microorganisms even in the HAART era reported that Salmonella spp. was the most common (7,8). pathogen, followed by E. coli and Staphylococcus HIV infection is associated with an increased risk of aureus (16). In contrast, a recent study on BSI among bloodstream infections (BSI) (9–11). Streptococcus HIV-infected outpatients in Cambodia, Thailand, and pneumoniae and Escherichia coli were the most com- Vietnam showed that Mycobacterium tuberculosis ac- mon Gram-positive and Gram-negative organisms iso- counted for 54z of infections, followed by fungi and lated from the bloodstream of hospitalized HIV-infect- bacteria (17). ed patients in the United States in 2001 (12). The Few studies have described the pattern of BSI and presence of BSI is associated with increases in mortality their clinical manifestations, which may have changed, rate, length of hospital stay, and the intensive care unit among HIV-infected patients in the HAART era in resource-limited settings. We aimed to determine the epidemiology of causative pathogens and the clinical *Corresponding author: Mailing address: Department of characteristics of HIV-infected patients with BSI in Medicine, Faculty of Medicine Ramathibodi Hospital, 270 Thailand. Factors associated with mycobacterial or fun- Rama VI Rd., Bangkok 10400, Thailand. Tel: ＋662 201 gal BSI and mortality were determined. These results 0033, Fax: ＋662 201 2232, E-mail: sasisopin.kie＠ may help health care providers prevent BSI and empiri- mahidol.ac.th cally select antimicrobial therapy while blood culture 28 results are pending. Table 1. Clinical characteristic of 140 HIV-infected patients who had bloodstream infection MATERIALS AND METHODS Characteristic n ＝ 140 Patients and population: A retrospective cohort study Mean (SD) age, years 38 (9.1) was conducted at Ramathibodi Hospital (a 1,000-bed Male gender, no. (z) 91 (65) university hospital in Bangkok, Thailand). Patients Route of HIV acquisition, no. (z) with a positive blood culture were identified from the Heterosexual 91 (65) database of the microbiology laboratory in the Depart- Unknown or other 49 (35) ment of Pathology between January 2004 and June Prior AIDS defining illness, no. (z) 83 (59.3) 2008. The study was approved by the institutional re- Tuberculosis 49 (43) view board. Inclusion criteria were as follows: (i) Æ15 Pneumocystis jiroveci pneumonia 24 (21) years of age, (ii) documented HIV infection, (iii) a diag- Cryptococcosis 13 (11.4) nosisofBSI,whichwasdefinedasanisolatedtrue Cytomegalovirus disease 6 (5.3) pathogen in one or more blood cultures with clinically Malignancy 4 (3.5) apparent signs and symptoms of infection. Patients Others 18 (15.8) were excluded if there was any evidence of blood culture Antiretroviral therapy, no. (z) 51 (36.4) contamination, which was defined as a single blood cul- NNRTI-based HAART regimen 40 ture yielding one of the following organisms: coagulase- PI-based HAART regimen 11 negative staphylococci, Corynebacterium spp., Bacillus Some patients had more than one prior opportunistic infection. spp., Propionibacterium spp., Peptostreptococcus spp., HAART, highly active antiretroviral therapy; NNRTI, nucleo- Clostridium spp., or unidentified Gram-positive rods, side reverse transcriptase inhibitor; PI, protease inhibitor; SD, standard deviation. or if the clinician did not initiate treatment, believing that it was not a true pathogen. Data collection: Medical records were retrieved and Table 2. Characteristic of bloodstream infection among 140 reviewed. The following variables were collected, (i) HIV-infected patients clinical characteristics, including gender, age, route of HIV acquisition, prior opportunistic infections, under- Characteristic n ＝ 140 lying conditions, and antiretroviral therapy, (ii) BSI, in- Causative pathogen, no. (z)1) cluding causative pathogen, type and site of infection, Gram-negative bacilli 57 (39.6) hospitalization, co-infection, complications, and out- Fungus 35 (24.3) come, (iii) laboratory-related data, including complete Mycobacterium spp. 29 (20.1) blood count, blood chemistry, CD4 cell count, HIV Gram-positive cocci and rod 23 (16.0) RNA, hepatitis B virus, and hepatitis C virus (HCV) Causative pathogen, no. (z)1) profile. Community-acquired infection was defined as a Cryptococcus neoformans 30 (20.8) positive blood culture that developed within 48 h of ad- Salmonella spp. 21 (14.6) mission, and nosocomial infection was defined as an in- Mycobacterium tuberculosis 17 (11.8) fection that developed after 48 h of hospitalization or Escherichia coli 14 (9.7) within 14 days of a previous hospitalization. Non-tuberculous mycobacteria 12 (8.3) Statistical analysis: Chi-square test or Fisher's exact Staphylococcus spp. 12 (8.3) test and Student's t test or Mann-Whitney U test were Klebsiella pneumoniae 4 (2.7) used to compare categorical variables and continuous Penicillium marneffei 4 (2.7) variables between the two groups, respectively. Logistic Streptococcus pneumoniae 2 (1.4) regression was used to determine the factors associated Other Streptococcus spp. 3 (2.1) with mycobacterial or fungal BSI and mortality. The Histoplasma capsulatum 1 (0.7) odds ratio (OR) and 95z confidence interval (CI) were Others 23 (16) estimated. Variables with P º 0.10 were considered in Focal site of infection, no. (z) 115 (82.2) the multivariate logistic regression model after assess- Central nervous system 34 (23.8) ment of multicollinearity of variance inflation factors. Respiratory tract 29 (20.3) Variables were selected from a multiple logistic regres- Intra-abdomen or gastrointestinal tract 26 (18.2) sion model with backward stepwise selection, and those Bone marrow 16 (11.2) that attained a level of significance were retained in the Lymph node 12 (8.4) model. A P value of º0.05 was considered statistically Urinary tract 11 (7.7) significant. All statistical analyses were performed using Skin and soft tissue 10 (7) Stata statistical software version 10.0 (Stata Corp., Col- Catheter-related 3 (2.1) lege Station, Texas, USA). Bone and joints 2 (1.4) 1): Some patients had more than one organism recovered from RESULTS blood culture. A total of 140 patients were included in the analysis. Their mean (standard deviation [SD]) age at BSI diag- illness (tuberculosis was the most common at 43z). nosis was 38 (9.1) years; 91 (65z) patients were male, 91 Overall, 7.1z and 12.8z of patients were positive for (65z) patients had heterosexual risk of HIV acquisi- HBsAg and anti-HCV, respectively, and 13.6z of tion, and 83 (59z) patients had a prior AIDS-defining patients had another underlying condition. Only 51 29 Table 3. Clinical characteristic of 140 HIV-infected patients who had bloodstream infection stratified by causative pathogen (mycobacteria or fungus versus bacteria) Mycobacteria Variable or fungus Bacteria P ＝ (n ＝ 64) (n 76) Clinical characteristics Mean (SD) age, years 35.7 (7.2) 39 (10) 0.021 Male gender, no.
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