ARTICLE IN PRESS American Journal of Infection Control ■■ (2015) ■■–■■

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American Journal of Infection Control

American Journal of Infection Control

j o u r n a l h o m e p a g e : w w w. a j i c j o u r n a l . o r g

Brief reports

Risk factors and outcomes of hospitalized patients with blood infections caused by multidrug-resistant Acinetobacter baumannii complex in a hospital of Northern China Ninghui Guo MM a, Wencheng Xue PhD b, Dahai Tang PhD c, Jinya Ding PhD d, Bin Zhao PhD e,* a

Postgraduate Training Base of General Hospital of Shenyang Military Area Command, Liaoning Medical University, Jinzhou, China Clinical Laboratory, General Hospital of Shenyang Military Area Command, Shenyang, China c Clinical Laboratory, Navy Hospital 411, Shanghai, China d Clinical Laboratory, General Hospital of Wuhan Military, Wuhan, China e Medical Department, General Hospital of Nanjing Military, Nanjing, China b

Key Words: Risk factors multidrug-resistant Acinetobacter baumannii complex bloodstream infections outcomes

The purpose of this study was to determine the risk factors and outcomes of bloodstream infections caused by multidrug-resistant (MDR) Acinetobacter baumannii complex in a hospital of Northern China. Risk factors associated with MDR A baumannii complex included older age, pneumonia, using drainage catheters, and intensive care unit stay. Multivariate analysis showed that multidrug resistance and mechanical ventilation were identified as independent risk factors for 30-day mortality in patients with A baumannii complex bacteremia. © 2015 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Acinetobacter baumannii complex (Abc) is an important nosocomial pathogen that has become an increasingly prevalent cause of bloodstream infections, ventilator-associated pneumonia, and surgical site infections.1 It has rapidly acquired resistance to multiple antimicrobial agents, indicating a high adaptability to the selective pressure from the broad-spectrum antimicrobial. The emergence of multidrug-resistant (MDR) Abc2 leads to high treatment failure and poses a great hazard to hospital-acquired infections control. The objective of this study is to determine the risk factors, outcomes, and prognosis of mortality with MDR Abc bacteremia in a tertiary hospital of Northern China. METHODS This retrospective study was conducted in the General Hospital of Shenyang Military during June 2012-June 2015. The blood samples were incubated using the automated BacT/ALERT system (bioMérieux, Marcy l’Etoile, France). The identification and

* Address correspondence to Bin Zhao, PhD, Medical Department, General Hospital of Nanjing Military, Zhongshan St, Xuanwu District, Nanjing, China, MD 210002. E-mail address: [email protected] (B. Zhao). Funding/Support: Supported by the Science and Technology Research Program in Liaoning Province (grant no. 2011225021). Conflicts of Interest: None to report.

antimicrobial susceptibility testing of the Abc isolates were performed by VITEK 2 compact (bioMérieux), and susceptibility testing of cefoperazone-sulbactam was performed using the manual disk diffusion method. The susceptibility results were interpreted in accordance with the Clinical and Laboratory Standards Institute. These included isolates were further divided into the following 2 groups: non–MDR Abc and MDR Abc. Patients The patients were identified through the hospital infection control database. Documented patient demographics and potential risk factors included age, sex, underlying diseases, duration of hospital stay, length of intensive care unit (ICU) stay, invasive devices (central venous catheter, mechanical ventilation, major surgeries, endotracheal intubation, urinary catheters, and drainage catheters), hemodialysis, septicemia, previous antibiotic use, outcomes of patients with Abc bacteremia, coinfection with other pathogens in the bloodstream, prior colonization with Abc, antibiotic susceptibility results, and level of serum albumin. Prior exposure to antimicrobial agents was defined as treatment for at least 24 hours within 30 days prior to Abc isolation. Multidrug resistance was defined as nonsusceptibility to ≥3 of the following groups of antimicrobials: aminoglycosides, antipseudomonal penicillins, carbapenems, cephalosporins, and

0196-6553/© 2015 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.ajic.2015.11.019

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Table 1 Comparison of demographic and clinical characteristics between patients with MDR Abc bacteremia and non–MDR Abc bacteremia using a multivariate analysis

Variables Age, mean ± SD (y) Underlying disease >30 d bedridden Pneumonia Shock Respiratory failure Prior colonization of Abc Invasive procedure CVA Mechanical ventilation Endotracheal intubation Urinary catheter Drainage catheter Stay in ICU Low albumin level Prior antibiotic usage Carbapenem Glycopeptide Tigecycline

Multivariate analysis

MDR Abc (n = 64)

Non–MDR Abc (n = 23)

OR

95% CI

P value

60.61 ± 20.63

55.83 ± 19.31

1.061

1.011-1.113

.016

27 39 14 12 42

4 1 0 0 5

— 60.432 — — —

— 2.754-1,325.957 — — —

.311 .009 .301 .687 .620

48 46 47 55 34 51 55

8 4 5 11 3 5 12

— — — — 7.516 11.954 —

— — — — 1.331-42.423 2.438-58.617 —

.064 .766 .367 .155 .022 .002 .875

41 20 11

4 0 0

— — —

— — —

.344 .155 .660

NOTE. Values are n or as otherwise indicated. Abc, Acinetobacter baumannii complex; CI, confidence interval; CVA, central venous catheter; ICU, intensive care unit; MDR, multidrug resistance; OR, odd ratio.

quinolones.3 Mortality was defined as a death occurring within 30 days after diagnosis of Abc. Data analysis was performed using SPSS 19.0 software (SPSS, Chicago, IL). Categorical variables were compared using the χ2 test or Fisher exact test. Variables with P < .10 in the univariate analysis were entered into a multivariate analysis using the multiple logistic regression method to determine the independent variables that were associated with multidrug resistance and mortality. All tests were 2-tailed, and P < .05 was considered significant. RESULTS During the study period, 87 patients with Abc bacteremia were isolated from the clinical specimens: 23 isolates (26.4%) were non– MDR Abc and 64 isolates (73.6%) were MDR Abc. MDR Abc was highly resistant to cephalosporins (98.9%), amikacin (64.4%), imipenem (62.1%), levofloxacin (54.0%), and trimethoprim-sulfamethoxazole (57.5%). Using univariate analysis, factors independently associated with MDR Abc bacteremia included >30 days bedridden, pneumonia, shock, respiratory failure, prior colonization of Abc, central venous catheter, mechanical ventilation, endotracheal intubation, urinary catheter, drainage catheter, ICU stay, low albumin level, and prior use of carbapenem, glycopeptide, and tigecycline. Multivariate analysis showed that older age (odds ratio [OR], 1.061; 95% confidence interval [CI], 1.011-1.113; P = .016), pneumonia (OR, 60.432; 95% CI, 2.754-1,325.957; P = .009), using drainage catheters (OR, 7.516; 95% CI 1.331-42.423; P = .022), and stay in the ICU (OR, 11.954; 95% CI, 2.438-58.617; P = .002) were independently associated with MDR Abc bacteremia (Table 1). The overall mortality rate was 44.8% (39/87); the mortality rate in MDR Abc was 59.4% (38/64). Multivariate analysis showed that multidrug resistance (OR, 26.355; 95% CI, 3.002-231.357; P = .003) and mechanical ventilation (OR, 11.568; 95% CI, 2.543-52.618; P = .002) were identified as independent risk factors for 30-day mortality in patients with Abc bacteremia (Table 2). DISCUSSION MDR Abc is a significant problem as seen in this study where 73.6% of isolates were considered MDR, and this rate is higher than

that in other countries.4 Our results shown that older age, pneumonia, using drainage catheters, and stay in the ICU were independent risk factors associated with MDR Abc bacteremia. Abc could easily survive for a long time in the environment and artificial devices. Bacteremia may develop after disruption of the skin and mucosa barrier of the patients through invasive procedures, providing a portal of entry for Abc. Using drainage catheters may lead to the patients being more vulnerable to infection by virulent pathogens though the open surgical wound. Patients in the ICU also had severe underlying diseases, cumulative burden of prior use of antibiotics, and suppressed immune states; these factors may lead to patients being more easily infected after initial colonization, which may occur through cross-transmission from health workers or invasive procedures after a prolonged hospital stay.5 A baumannii bacteremia is associated with a high mortality rate, ranging from 29%-46.9%.6,7 Our studies shown that patients with MDR Abc bacteremia had a higher mortality rate than patients with non– MDR Abc (59.4% vs 4.3%). A diverse spectrum of comorbidities have been investigated as potential risk factors for mortality in these patients, such as the severity of underlying diseases, pneumonia, recent surgery, septic shock, disseminated intravascular coagulation, resistance to carbapenems, and mechanical ventilation.8-10 Compatible with these reports, we revealed that multidrug resistance and mechanical ventilation were statistically significant risk factors associated with 30-day mortality. The influence of drug resistance on the mortality of patients infected with Abc is still subject to debate. Currently, the combination therapy regimen, carbapenem plus sulbactam, is usually adopted in the face of MDR Abc bacteremia. However, the effect of this regimen is not ideal. Polymyxins and tigecycline have been served as the last defenders against MDR Abc infections in most clinical departments,11 but they are very costly and not readily available in developing countries. In our hospital, patients with MDR Abc bacteremia were treated with the regimen as previously mentioned according to the patients’ health conditions and economic capacity, but the prognosis of these patients was still worse. Our results suggest that multidrug resistance and critically ill patients with mechanical ventilation contribute to an increased risk of mortality. Therefore, the timely and appropriate antimicrobial treatment of MDR Abc bacteremia is not enough; the implementation of infection control strategies (eg, barrier precautions) plays a key role to

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Table 2 Risk factors for 30-day mortality among patients infected with Abc bacteremia

Variables Age, mean ± SD (y) MDR Underlying disease >30 d bedridden Pneumonia Shock Respiratory failure Prior colonization of Abc Invasive procedure CVA Mechanical ventilation Endotracheal intubation Urinary catheter Drainage catheter Stay in ICU Low albumin level

Multivariate analysis

Mortality (n = 39)

Survival (n = 48)

OR

95% CI

P value

62.44 ± 20.10 38

56.83 ± 20.29 26

— 26.355

— 3.002-231.357

.458 .003

13 24 11 10 28

18 16 3 2 19

— — — — —

— — — — —

.057 .594 .329 .867 .430

29 32 31 36 17 22 35

27 18 21 30 20 34 32

— 11.568 — — — — —

— 2.543-52.618 — — — — —

.699 .002 .505 .240 .057 .333 .268

NOTE. Values are n or as otherwise indicated. Abc, Acinetobacter baumannii complex; CI, confidence interval; CVA, central venous catheter; ICU, intensive care unit; MDR, multidrug resistance; OR, odd ratio.

combat these persistent infections, especially in critically ill patients. The urgent work is to spread the knowledge of the risk factors to health workers and prevent the transmission of MDR Abc isolates in the hospital. This study has several limitations. Because of its retrospective nature, it is difficult to infer causation because of possible unmeasured factors and limited completeness of documentation. Moreover, we did not conduct molecular-level analysis to assess the source of infection. Finally, this was a single-center study, our study may not be generalizable to other settings.

Acknowledgments We thank Jing Yang, General Hospital of Shenyang Military, China, for assistance in data analysis and review of the manuscript.

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