Acinetobacter baumannii Infection and Colonization among Pediatric Patients at Chiang Mai University Hospital

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1 Original Article Vol. 24 No. 2 Acinetobacter baumannii infection among pediatric patients;- Oberdorfer P & Oberdorfer P. 63 Acinetobacter baumannii Infection and Colonization among Pediatric Patients at Chiang Mai University Hospital Kanokorn Leepethacharat, M.D., Peninnah Oberdorfer, M.D., Ph.D. ABSTRACT Acinetobacter baumannii is a Gram-negative coccobacillus that causes outbreaks of nosocomial infections, especially in intensive care units. Risk factors for these infections are not well established. We undertook a retrospective review of the medical records of all pediatric patients hospitalized at Chiang Mai University Hospital with positive culture results for A. baumannii from January 2002 to December Eighty-four cases of A. baumannii were identified from 132 specimens positive for A. baumannii, and classified as infected (52 of 84 cases) or colonized (32 of 84 cases). The prevalence of infection and colonization was 1.4 percent. Prior to infection, 83.3 percent of the patients had been previously prescribed antibiotics, and 94 percent were either on ventilator or had an indwelling catheter. A. baumannii was highly susceptible to colistin, with 96.4 percent of isolates susceptible. Patients diagnosed with hematological conditions were more likely to have infections than colonizations (p=0.019). The overall mortality rate was 21.4 percent. Health care providers should be aware of these factors to help reduce infection rates. (J Infect Dis Antimicrob Agents 2007;24:63-73.) INTRODUCTION Acinetobacter baumannii is a pleomorphic, aerobic Gram-negative coccobacillus frequently isolated from hospital environments and hospitalized patients. As a water organism it preferentially colonizes aquatic environments, but can also survive for long periods of time on dry surfaces. 1-2 Infected patients commonly develop bacteremia from the respiratory tract (71% of patients); 25 percent develop septic shock; and 30 percent develop disseminated intravascular coagulation. 3 Worldwide, the incidence rates of A. baumannii infections vary considerably. In Spain, a 12-month study from January 1993 to 1994 reported 1.8 episodes of A. baumannii bacteremia per 1,000 adults admitted to the hospital in Seville. 3 In the United States, the Department Division of Infectious Diseases, Department of Pediatric, Faculty of Medicine, Chiang Mai University, Chiang Mai 50002, Thailand. Received for publication: January 1, Reprint request: Peninnah, M.D., Ph.D., Division of Infectious Diseases, Department of Pediatric, Faculty of Medicine, Chiang Mai University, Chiang Mai 50002, Thailand. aoberdor@mail.med.cmu.ac.th Keyword: Acinetobacter baumannii, pediatric patients, infection 63

2 64 J INFECT DIS ANTIMICROB AGENTS May-Aug of Medicine at Vanderbilt University School of Medicine, Nashville, Tennessee, reported the baseline attack rate of multidrug-resistant A. baumannii nosocomial infections from August 1997 to January 1998 to be 3 per 100 patients per month. 4 During an outbreak from February 1 to March 22, 1998, the attack rate rose to 16 per 100 patients per month. 3 In Taiwan, a rapid increase in the incidence of pandrug-resistant A. baumannii (from 5.88% in 1993 to 21.5% in 2000) and multidrug-resistant A. baumannii (0% before 1998 to 6.5% in 2000) has been described. 5 In Greece, three patients were infected, and two were colonized with multidrug-resistant A. baumannii within a period of one week in July 2000 at the intensive care unit (ICU) of the University of Ioaanina. 6 Although classically described as a nosocomial pathogen in adults 6-8, A. baumannii is emerging as an important pathogen in neonates. Numerous outbreaks among neonates, particularly in ICUs, have been reported. In Israel from June to September 1999, eleven infants, all in the ICU and all with very low birth weight, developed sepsis due to A. baumannii. 9 Again in Taiwan, at the neonatal ICU at the Chang Gung Children s Hospital, six premature infants developed sepsis between August and September 2000, with three additional cases infected during November and December Several factors have been associated with A. baumannii infection, including prolonged hospitalization, ICU admission, mechanical ventilation, invasive procedures, and the use of broad-spectrum antimicrobials. 11 Outbreaks of A. baumannii have been associated with colonization of the organism on medical equipment, intravenous catheters, gloves, and napkins. 12 A. baumannii colonization may lead to subsequent infection. Struelens and colleagues reported that within three weeks, two of four patients with a mechanical ventilator who were colonized with A. baumannii developed pneumonia. 13 A development of antimicrobial resistance has made antibiotic control and treatment of A. baumannii infections increasingly difficult. Cisneros and colleagues reported that in 1999 at Hospital Universitario Virgen del Rocio, Sevilla, Spain, 100 percent of A. baumannii isolates in the blood were susceptible to imipenem, whereas by the year 2000, 50 percent had developed resistance. 11 Lai and colleagues reported that in a retrospective study of 36 patients with A. baumannii bacteremia between January 1996 and December 1997 at China Medical College Hospital in Taichung, Taiwan, all isolates were resistant to ampicillin, cephalothin, cefonicid, and moxalactam. Nineteen percent of isolates were also resistant to imipenem. 7 Another study that examined antibiotic resistance patterns of common sepsiscausing pathogens in neonates. They found a resistance of A. baumannii to gentamicin was as high as percent. 14 Moreover, A. baumannii susceptibility to antimicrobials has been shown to vary considerably among countries, between hospitals, and even among the wards of the same hospital. 3,7,15 In treating A. baumannii infections, Cisneros and colleagues reported that the treatment with imipenem was most effective (the cure rate of 87.5%). 3 Lopez- Hernandez and colleagues reported the greatest susceptibility of A. baumannii isolates to colistin (100%), imipenem (84.4%), meropenem (88.4%), and ampicillin-sulbactam (84.6%). 16 Rodriguez-Hernandez and colleagues reported that a combined treatment with imipenem and amikacin was no more effective than a treatment with imipenem alone in the clearance of A. baumannii from the lungs. 15 In the United States, Jellison and colleagues reported ampicillin-sulbactam to be at least as effective as imipenem-cilastatin, based on clinical response at the end of treatment, and suggested its use as a cost-effective alternative treatment option. 17

3 Vol. 24 No. 2 Acinetobacter baumannii infection among pediatric patients;- Oberdorfer P & Oberdorfer P. 65 A. baumannii outbreaks may be prevented and also controlled by staff education, stricter adherence to barrier precautions and hand washing regimes. 9,10,14,18 Cardoso and colleagues reported that 70 percent ethyl alcohol and 10 percent providoneiodine may be the most effective agents for the removal of A. baumannii from the heavily contaminated hands. 18 It has also been reported that outbreaks can be stopped through rapid and thorough environmental investigations to find the source of infection, followed by infection control measures. 9 In Chiang Mai University Hospital, the prevalence of A. baumannii in blood cultures has increased over the previous five years, increasing from a ranking of the fifth in the prevalence in 1999 and the fourth in 2001 to the third in Over this period, the susceptibility of A. baumannii to common antimicrobials decreased significantly. Imipenem susceptibility fell from 100 percent to 43 percent, and cefoperazone-sulbactam susceptibility fell from 91 percent to 59 percent. 19 To further investigate the prevalence and antimicrobial susceptibility, we retrospectively reviewed all cases of A. baumannii in the pediatric wards of Chiang Mai University Hospital, Chiang Mai, Thailand from January 2002 to December Objectives This study was aimed to determine the prevalence of, clinical manifestations of, and factors associated with A. baumannii infection and colonization. We also aimed to examine the antibiotic susceptibility patients of A. baumannii. METHODS Setting and participants This study was conducted at Chiang Mai University Hospital, Chiang Mai, Thailand, among 65 pediatric patients aged 15 years or less who were hospitalized in the pediatric wards from January 2002 to December 2003 and also had positive culture results for A. baumannii from any specimen (the blood, sputum, urine, body fluid, or wound). The definition of infection was the combination of clinical manifestations and results of laboratory and other tests. 20 The definition of colonization was the presence of microorganisms (on skin, mucous membranes, in open wounds, or in a excretions or secretions) that are not causing adverse clinical signs or symptoms. 20 Procedures Using the hospital computer system, we performed a database search for positive culture results for A. baumannii. The medical records of each patient identified by this search were reviewed by history (age, gender, underlying disease, and diagnosis), source of the specimen that tested positive for A. baumannii, the antimicrobial susceptibility patterns for A. baumannii, and patient outcome. Data analysis The descriptive and comparative statistical analyses were performed using the statistical program Epi Info Data describing demographics, clinical presentations, treatment, susceptibility, and outcome were reported as proportions. Chi-square tests were used to assess the univariate relationships between the demographic data and clinical presentations, treatment, susceptibility, and outcomes. RESULTS Demographic data Over the twenty-four months reviewed, 7,190 children were admitted to Chiang Mai University Hospital, and 101 patients (1.4%) had positive cultures

4 66 J INFECT DIS ANTIMICROB AGENTS May-Aug for A. baumannii from at least one specimen. Data from 84 patients were available from 132 A. baumannii positive-specimens. Forty-nine (58.3%) were male, and 35 (41.7%) were female. The mean age was 3 ± 3.7 years (range: 1 day to 13 years). The overall prevalence of A. baumannii infection and colonization was 1.4 percent (62% of patients were classified as infected and 58.3% colonized). There were no significant differences in demographic characteristics between the infected and colonized group (Table 1). Most patients were hospitalized to either the pediatric (46%) or the neonatal ICUs (11.9%). The number of children with (43 patients) and without (41 patients) underlying disease was similar. The most common underlying disease was congenital heart disease (13 patients, 30.2%). Other common underlying conditions were malignancy (8, 18.6%), preterm birth (7, 16.2%), and HIV infection (5, 11.6%). Clinical presentations The most common clinical presentation of all patients that brought the children to the hospital was respiratory symptoms (26 patients, 31%). Others presented with fever (22 patients, 26.2%), neurological Table 1. Demographic data of 84 pediatric patients with Acinetobacter baumannii infection or colonization. Demographic data Total (N=84) Infection (N=52) Colonization (N=32) P-value Age (mean ± SD) (year) 3 ± ± ± Sex (N, %) - Boys 49 (58.3) 32 (61.5) 17 (53.1) Girls 35 (41.7) 20 (38.5) 15 (46.9) Wards (N, %) - Pediatric intensive care units 46 (54.7) 29 (55.7) 17 (53.1) Neanatal intensive care unit 10 (11.9) 5 (9.6) 5 (15.6) Pediatric wards 23 (27.3) 15 (28.8) 8 (25.0) Nursery wards 5 (5.9) 3 (5.7) 2 (6.25) Underlying diseases (N, %) 43 (51.2) 24 (46.1) 19 (59.4) Congenital heart disease 13 (30.2) 7 (29.1) 6 (3.15) Malignancy 8 (18.6) 6 (25.0) 2 (10.5) Preterm 7 (16.2) 4 (16.7) 3 (15.8) HIV 5 (11.6) 4 (16.7) 1 (5.2) Renal disease 3 (7.0) 1 (4.2) 2 (10.5) Neurological disease 3 (7.0) 1 (4.2) 2 (10.5) Respiratory disease 2 (4.7) 1 (4.2) 1 (5.2) Connective tissue disease/sle 1 (2.3) 0 (0.0) 1 (5.2) Hematologic disease 1 (2.3) 0 (0.0) 1 (5.2) N: number, SLE: systemic lupus erythematosis, HIV: human immunodeficiency virus

5 Vol. 24 No. 2 Acinetobacter baumannii infection among pediatric patients;- Oberdorfer P & Oberdorfer P. 67 symptoms (10 patients, 11.9%), and gastrointestinal symptoms (5 patients, 6.0%). Fourteen percent came to the hospital by appointments, and 3.6 percent were newborns. The most common diagnosis was pneumonia (18 patients, 21.4%). Other diagnoses were hematological/ oncological disease (19%), cardiovascular disease (19%), neurological disease (13%), gastrointestinal disease (13%), allergic disease (2.4%), and renal disease (3.6%). Specific diagnosis There were no significant differences between the infected and colonized groups in the frequency of specific diagnoses, with the exception of hematologic/ oncologic disease, which was more frequent in the infected group with a P-value of (Table 2). The factors associated with A. baumannii infection or colonization. The factors associated with A. baumannii infection or colonization were 1) illness for at least two weeks before specimen collection (44 patients, 52.4%), including pneumonia (35.7%), febrile pneumonia (8.3%), sepsis (4.8%), urinary tract infection (2.4%), diarrhea (2.4%), and skin infection (1.2 %); 2) prior use of antibiotics (83.3%), including cephalosporins (76.2%), aminoglycosides (48.8%), penicillins (45.2%), metronidazole (16.7%), and carbapenems (8.3%); and 3) use of medical equipment including indwelling vascular catheters (91.7%), nasogastric tubes (63.1%), mechanical ventilators (59.5%), urinary catheters (23.8%), intercostal drainage tubes (7.1%), and central lines (6%). When comparing the associated risk factors between the infected and colonized group, the colonized group was more likely to have had a nasogastric tube inserted (Table 3), with a P-value of Antibiotic susceptibility of A. baumannii The clinical specimens were mainly isolated from the respiratory tract (64.3%), and other specimens were isolated from the blood, (14.3%), the pus (11.9%), the urine (4.8%), the catheter tip (2.4%), the cerebrospinal fluid (1.2%), and the peritoneal fluid (1.2 %) (Table 4). Table 2. The diagnosis of patients with Acinetobacter baumannii infection or colonization. Diagnosis Total Infection Colonization (N, %) P-value Pulmonary diseases 20 (23.8) 15 (28.8) 5 (15.6) Hematologic or oncologic diseases 16 (19.0) 14 (26.9) 2 (6.25) Cardiovascular diseases 16 (19.0) 8 (5.3) 8 (25.0) Neurological diseases 11 (13.0) 7 (13.4) 4 (12.5) Gastrointestinal diseases 11 (13.0) 4 (7.7) 7 (21.9) Allergic diseases 2 (2.4) 2 (3.8) 0 (0.0) Renal diseases 3 (3.6) 1 (1.9) 2 (6.25) Others 4 (6.0) 1 (1.9) 4 (12.45) N: number 67

6 68 J INFECT DIS ANTIMICROB AGENTS May-Aug Table 3. The factors associated with Acinetobacter baumannii infections and colonization. Factors Total Infection Colonization (N, %) P-value Complication during hospitalization 44 (52.4) 24 (46.2) 20 (62.5) Pneumonia 30 (35.7) 17 (70.8) 13 (65.0) Febrile neutropenia 7 (8.3) 5 (20.8) 2 (10.0) Sepsis 4 (4.8) 2 (8.3) 2 (10.0) Urinary tract infection 2 (2.4) 2 (8.3) 0 (0.0) Diarrhea 2 (2.4) 2 (8.3) 0 (0.0) Infected wound 1 (1.2) 1 (4.2) 0 (0.0) Prior use of antibiotics 71 (84.5) 42 (80.7) 29 (90.6) The use of medical equipments 79 (94.0) 47 (90.3) 32 (100) Indwelling vascular catheters 77 (91.7) 47 (90.3) 30 (93.7) Nasogastric tubes 53 (63.1) 28 (53.8) 25 (78.1) Mechanical ventilators 50 (59.5) 28 (53.8) 22 (68.7) Urinary catheters 20 (23.8) 11 (21.1) 9 (28.1) Intercostal drained tubes 6 (7.1) 5 (9.6) 1 (3.1) Central lines 5 (6.0) 3 (5.7) 2 (6.2) Table 4. The sites of culture specimens positive for Acinetobacter baumannii. Specimens Total Infection Colonization (N, %) P-value Sputum/bronchoalveolar lavage 54 (64.3) 34 (65.3) 20 (62.5) Blood 12 (14.3) 7 (13.5) 5 (15.6) Pus 10 (11.9) 7 (13.5) 3 (9.4) Urine 4 (4.8) 3 (5.8) 1 (3.1) Tip of catheter 2 (2.4) 0 (0.0) 2 (6.2) Cerebrospinal fluid 1 (1.2) 1 (1.9) 0 (0.0) Peritoneal fluid 1 (1.2) 0 (0.0) 1 (3.1) A. baumannii was highly susceptible to colistin (96.4%). It was also susceptible to cefoperazonesulbactam (76.6%), imipenem (64.5%), meropenem (52.4%), netilmicin (48.5%), ciprofloxacin (34.0%), amikacin (33.1%), gentamicin (30.2%), ceftazidime (27.7%), piperacillin (26.2%), cefepime (24.7%), and cefpirome (21.1 %) (Figure 1). The antibiotic susceptibility pattern was similar for organisms from both the

7 Vol. 24 No. 2 Acinetobacter baumannii infection among pediatric patients;- Oberdorfer P & Oberdorfer P. 69 infected and colonized groups (Figures 2 and 3). The mean duration of hospitalization was 53 days. The overall mortality rate was 21.4 percent. DISCUSSION This study found that the prevalence of A. baumannii infection and colonization in Chiang Mai University Hospital between January 2002 and December 2003 was 1.4 percent. Factors associated with A. baumannii was 1.4 percent infection or colonization were ICU admission, pneumonia, use of catheters or ventilators, and prior antibiotic use. A. baumannii was highly susceptible to colistin. The overall mortality rate was 21.4 percent. 100 Percent Resistant Intermediate Susceptibility 0 Colistin Gentamicin Netilmicin Amikacin Piperacillin Cefotaxime Cefoperazone/sulbactam Ceftazidime Imipenem Ciprofloxacin Meropenem Cefepime Cefpirome Piperacillin/tazobactam Drugs Figure 1. Antimicrobial susceptibility pattern of Acinetobacter baumannii. Percents Percent 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 0 Resistant resistant Intermediate intermediate Susceptibility susceptibility Colistin colistin Gentamicin gentamicin Netilmicin netilmicin Amikacin amikacin Piperacillin piperacillin Cefotaxime cefotaxime Drugs Cefoperazone/sulbactam cefoperazone/sulbactam Ceftazidime ceftazidime Imipenem imipenem Ciprofloxacin ciprofloxacin Meropenem meropenem Cefepime maxipime Cefpirome cefpirome Piperacillin/tazobactam piperacillin/tazobactam Drugs Figure 2. Antimicrobial susceptibility pattern of Acinetobacter baumannii in 52 paediatric patients in the infected group. 69

8 70 J INFECT DIS ANTIMICROB AGENTS May-Aug Percent Resistant Intermediate Susceptibility Colistin Gentamicin Netilmicin Amikacin Piperacillin Cefotaxime Cefoperazone/sulbactam Ceftazidime Imipenem Ciprofloxacin Meropenem Cefepime Cefpirome Piperacillin/tazobactam Drugs Figure 3. Susceptibility of colonized groups to antibiotics. The majority of patients were admitted to the ICUs (66.6%). In comparison, a similar study by the Medical Department of Chiang Mai University Hospital in 2003s found 43 percent of patients were hospitalized in the ICUs or sub-icus. 21 In Germany, 91 percent of patients were hospitalized to the ICUs. 8 About half of the patients in this study with A. baumannii infection or colonization had underlying disease, of which congenital heart disease was the most common (15.5%). In China, malignancy was the major underlying disease (34.8%). 7 In the Medical Department of Chiang Mai University Hospital, the most common underlying disease was hypertension (21%). 21 However, the study of Mahgoub and colleagues found that the underlying diseases including malignancy and respiratory tract disease did not increase the risk of infection. 22 The main symptoms were respiratory symptoms (31%) and fever (21.4%). Factors associated with A. baumannii infection or colonization were pneumonia (35.7%), prior antibiotic use (83.3%), and the use of medical equipment (94%) including indwelling vascular catheters, nasogastric tubes, and mechanical ventilators. These findings were similar to those of Koprnova and colleagues 23 which found that the use of mechanical ventilators and prior antibiotic use were associated with A. bamannii bacteremia (p< and p<0.01, respectively). Seifert and colleagues 8 reported that among patients with A. baumannii infection or colonization, 99 percent had used indwelling vascular catheters, 81 percent had prior broad-spectrum antibiotic use, and 70 percent had used mechanical ventilators. 8 In contrast, Chaiwarith and colleagues found that the use of mechanical ventilators, central venous catheters, or urinary catheters did not increase the risk of A. baumannii infection. 21 Most positive specimens were from the respiratory tracts, followed by the blood specimens. From this results, we concluded that the most common presentation of A. baumannii infection was pneumonia, followed by sepsis, similar to the findings of Cisneros and colleagues.

9 Vol. 24 No. 2 Acinetobacter baumannii infection among pediatric patients;- Oberdorfer P & Oberdorfer P. 71 A. baumannii was highly susceptible to colistin, with 96.4 percent of isolates susceptible. Other antibiotics with greater than 50 percent susceptibility were cefoperazone-sulbactam, imipenem, and meropenem (76.6%, 64.5%, and 52.4%, respectively). Chaiwarith and colleagues, in a study with the Medical Department of Chiang Mai University Hospital from July to October , also found that A. baumannii was most susceptible to colistin (98.9%), followed by netilmicin (85%), in disagreement with our results. Lopez-Hernandez and colleagues found that the susceptibility of A. baumannii to colistin, imipenem, and meropenem was 100 percent, 88.4 percent, and 88.4 percent, respectively. 16 The mean duration of hospitalization was 53 days, with an overall mortality rate of 21.4 percent. The previously reported mortality rate among patients with A. baumannii infection or colonization varies widely, ranging from 12.5 percent to 52 percent (Table 5). This study was the first among pediatric patients in Thailand. The major limitation of the study is that it was retrospective in design, and thus only 64 percent of the patient medical records could be located. Prospective studies are warranted. CONCLUSION The factors associated with A. baumannii infection or colonization were ICU admission, pneumonia, use of medical equipment, and prior antibiotic use. A. baumannii was most susceptible to colistin, followed by cefoperazone-sulbactam. The most common diagnosis was pneumonia, although this may be a biased finding since the most frequent site of positive specimen collection was from the respiratory tract. The overall mortality rate was 21.4 percent. This study should benefit the future care of patients with A. baumannii infections, helping to inform antibiotic selection and providing information to assist in reducing 71 risks associated with A. baumannii infection. We encourage health care workers to reduce infection rates by decreasing risks of infection such as avoiding prolonged use of antibiotics or medical equipments as well as strictly following infection control guidelines. Evidence-based interventions to reduce infections should be further implemented. References 1. Wendt C, Dietze B, Dietz E, Ruden H. Survival of Acinetobacter baumannii on dry surfaces. J Clin Microbiol 1997;35: Cunha BA. Acinetobacter. Last Updated: July 7, 2006 [cited 2007 Mar 1]. Available from: emedicine.com/med/topic3456.htm. 3. Cisneros JM, Reyes MJ, Pachon J, et al. Bacteremia due to Acinetobacter baumannii: epidemiology, clinical findings, and prognostic features. Clin Infect Dis 1996;22: D Agata EM, Thayer V, Schaffner W. An outbreak of Acinetobacter baumannii: the importance of crosstransmission. Infect Control Hosp Epidemiol 2000;21: Hsueh PR, Teng LJ, Chen CY, et al. Pandrug-resistant Acinetobacter baumannii causing nosocomial infections in a university hospital, Taiwan. Emerg Infect Dis 2002;8: Levidiotou S, Galanakis E, Vrioni G, Papamichael D, Nakos G, Stefanou D. A multi-resistant Acinetobacter baumannii outbreak in a general intensive care unit. In Vivo 2002;16: Lai SW, Ng KC, Yu WL, Liu CS, Lai MM, Lin CC. Acinetobacter baumannii bloodstream infection: clinical features and antimicrobial susceptibilities of isolates. Kaohsiung J Med Sci 1999;15: Seifert H, Strate A, Pulverer G. Nosocomial bacteremia due to Acinetobacter baumannii. Clinical features, epidemiology, and predictors of

10 72 J INFECT DIS ANTIMICROB AGENTS May-Aug Table 5. A comparison of Acinetobacter baumannii infection and colonization in this study and other studies. This study Chaiwarith and colleagues 21 del Mar Tomas and colleagues 24 Study period January 2002 to December 2003 July 2003 to 0ctober 2003 October 2001 to August 2003 Study design Retrospective Prospective Prospective Patients characteristics - Number of patients Number of specimens N - Age (means ± SD) (year) 3 ± ± Sex (male:female) 58:42 55:45 80:20 Underlying diseases (%) Sites of specimens (%) - Sputum/bronchoalveolar lavage Blood NA - Pus NA - Urine NA - Body fluid NA - Tip of catheter NA Infection: colonization 62:38 NA 46.7:53.3 Antibiotic susceptibility (%) Colistin (96.4) Colistin (98.9) NA Netilmicin (85) Means duration of hospitalization N (day) Mortality rate (%) NA: not applicable mortality. Medicine (Baltimore) 1995;74: Melamed R, Greenberg D, Porat N, et al. Successful control of an Acinetobacter baumannii outbreak in a neonatal intensive care unit. J Hosp Infect 2003;53: Huang YC, Su LH, Wu TL, et al. Outbreak of Acinetobacter baumannii bacteremia in a neonatal intensive care unit: clinical implications and genotyping analysis. Pediatr Infect Dis J 2002;21: Cisneros JM, Rodriguez-Bano J. Nosocomial bacteremia due to Acinetobacter baumannii: epidemiology, clinical features and treatment. Clin Microbiol Infect 2002;8: Armando G. Acinetobacter. In: Fletcher J, ed. Textbook

11 Vol. 24 No. 2 Acinetobacter baumannii infection among pediatric patients;- Oberdorfer P & Oberdorfer P. 73 of Pediatric Infectious Diseases. Philadelphia: Saunders, 2004: Struelens MJ, Carlier E, Maes N, Serruys E, Quint WG, van Belkum A. Nosocomial colonization and infection with multiresistant Acinetobacter baumannii: outbreak delineation using DNA macrorestriction analysis and PCR-fingerprinting. J Hosp Infect 1993;25: Roberts SA, Findlay R, Lang SD. Investigation of an outbreak of multi-drug resistant Acinetobacter baumannii in an intensive care burns unit. J Hosp Infect 2001;48: Rodriguez-Hernandez MJ, Pachon J, Pichardo C, et al. Imipenem, doxycycline and amikacin in monotherapy and in combination in Acinetobacter baumannii experimental pneumonia. J Antimicrob Chemother 2000;45: Lopez-Hernandez S, Alarcon T, Lopez-Brea M. Evolution of antimicrobial susceptibility of Acinetobacter baumannii clinical isolates. Rev Esp Quimioter 2000;13: Jellison TK, Mckinnon PS, Rybak MJ. Epidemiology, resistance, and outcomes of Acinetobacter baumannii bacteremia treated with imipenem-cilastatin or ampicillin-sulbactam. Pharmacotherapy 2001;21: Cardoso CL, Pereira HH, Zequim JC, Guilhermetti M. Effectiveness of hand-cleansing agents for removing Acinetobacter baumannii strain from contaminated hands. Am J Infect Control 1999;27: Oberdorfer A, Boonchu M. Bacterial isolates in blood cultures at the Chiang Mai University Hospital from 1999 to 2003: Changes in prevalence and drug susceptibility. Poster presentation. 9 th Western Pacific Congress on Chemotherapy and Infectious Diseases. 9 th WPCCID; December 1-5, 2004; Queen Sirikit National Convention Center. Bangkok, Thailand. 20. Garner JS, Jarvis WR, Emori TG, Horan TC, Hughes JM. CDC definitions for nosocomial infections, Am J Infect Control 1988;16: Chaiwanth R, Mahatthanaphak S, Boonchoo M, Supparatpinyo K, Sirisanthana T. Pandrug-resistant Acinetobacter baumannii at Maharaj Nakorn Chiang Mai Hospital. J Infect Dis Antimicrob Agents 2005;22: Mahgoub S, Ahmed J, Glatt AE. Underlying characteristics of patients harboring highly resistant Acinetobacter baumannii. Am J Infect Control 2002;30: Koprnova J, Svetlansky I, Babel a R, et al. Prospective study of antibacterial susceptibility, risk factors and outcome of 157 episodes of Acinetobacter baumannii bacteremia in 1999 in Slovakia. Scand J Infect Dis 2001;33: del Mar TM, Cartelle M, Pertega S, et al. Hospital outbreak caused by a carbapenem-resistant strain of Acinetobacter baumannii: patient prognosis and riskfactors for colonisation and infection. Clin Microbiol Infect 2005;11:

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