Control and Elimination of Extensively Drug-Resistant Acinetobacter baumanii in an Intensive Care Unit

We decreased antimicrobial drug consumption in an intensive care unit in Lebanon by changing to colistin monotherapy for extensively drug-resistant Acinetobacter baumanii infections. We saw a 78% decrease of A. baumanii in sputum and near-elimination of blaoxa-23-carrying sequence type 2 clone over the 1-year study. Non–A. baumanii multidrug-resistant infections remained stable.


The Study
The ASP, ID team, and intensive care unit (ICU) physicians approved a plan to reduce use of empiric carbapenems in the ICU and use colistin, tigecycline, or both for patients confirmed with or at high risk for A. baumanii infections. ID physicians evaluated the clinical severity and hemodynamic stability of each patient and had final discretion to prescribe either colistin or tigecycline.
We included all ICU admissions in the study, even recurrent admissions. This ICU has a multidrug-resistant organism surveillance program that collects a sputum sample for culture every third day for intubated patients with abundant secretions. We used these cultures for our evaluation. We considered any culture sample outside this practice a duplicate and excluded it from our analysis. During the study period, we did not modify infection control practices. The study was approved by the institutional review board of SGHUMC.
We retrieved data from the hospital's computerized ordering system and examined medical records of all ICU admissions during February 1, 2016-January 31, 2017. Clinical data included patient demographics, admission diagnosis, and presence of mechanical ventilation. During February 1-June 30, 2016 (period 1), patients received colistin/carbapenem combination therapy for A. baumanii infections. During July 1, 2016-January 31, 2017 (period 2), we applied our intervention. We recorded the total number of bacterial cultures collected from the ICU and noted the site and date of sampling.
We considered the isolation density the number of clinical isolates/1,000 patient-days and the rate of ventilator-associated pneumonia (VAP) the number of VAP events/1,000 patient-days. We defined variables according to guidelines for XDR A. baumanii from the US Centers for Disease Control and Prevention and World Health Organization (10). We calculated case-fatality and VAP rates following guidelines from the American Thoracic Society and Infectious Diseases Society of America (11). We grouped antimicrobial drugs into 5 categories: group 1, antimicrobial drugs that do not require ID preapproval, such as third-generation cephalosporins, amoxicillin/clavulanic acid, and quinolones; group 2, oral vancomycin and metronidazole used for Clostridioides difficile therapy; group 3, imipenem and meropenem; group 4, broad-spectrum carbapenem-sparing regimens, including piperacillin/tazobactam, cefepime, ceftazidime, amikacin; and group 5, the XDR A. baumanii-active antimicrobial drugs colistin and tigecycline. We measured antimicrobial drug consumption by DDD per 1,000 patient-days (Table 1).

Control and Elimination of Extensively
We sent 48 laboratory-confirmed A. baumanii isolates, 31 collected during period 1 and 17 during period 2, to IHU-Méditerranée Infection, Aix-Marseille, France, for testing. Samples underwent 4 types of testing: matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (Microflex; Bruker Daltonics, https://www.bruker.com); antimicrobial susceptibility testing by disk diffusion method and interpreted according to the European Committee of Antimicrobial Susceptibility Testing 2017; real-time PCR to screen for carbapenemase-encoding genes; and multilocus sequence typing to determine genetic relationships among the isolates.
The ICU admitted 536 patients during the study period; 3 were readmissions. Patient characteristics between the 2 periods were statistically similar (Table 1). Throughout the study, the incidence of A. baumanii VAP decreased from 154.9 to 38/1,000 patient-days (p = 0.007) and the A. baumanii VAP case-fatality ratio dropped from 79 to 12/1,000 patient-days. Non-A. baumanii VAP incidence decreased from 62 to 51/1,000 patient-days. ICU mortality rates from all causes remained unchanged between period 1 and period 2 ( Table 1).

Conclusions
Our prudent use of antimicrobial drugs did not increase mortality rates and had a dramatic effect on antimicrobial consumption and MDR A. baumanii isolate density. A longer study period and larger sample likely would reveal additional effects on XDR infections and outcomes. Many factors could have affected the study results, including patient referrals and seasonality. However, the microbiological findings strongly point to high rates of carbapenem consumption as a sustaining factor in survival of XDR A. baumanii ST2 in our facility. By reducing carbapenem consumption, we broke a vicious cycle.
In the era where clinicians must manage severely ill, MDR-colonized patients, relying on existing guidelines is not enough. A creative, multidisciplinary approach with knowledge of local epidemiology is key to controlling MDR and XDR infections. Investing time in accurate diagnosis and implementing targeted carbapenem-sparing strategies for initial treatment is only possible through trusted collaboration between ID and ICU physicians. The dedication of the ASP and microbiology  departments at this facility is an example of a successful active surveillance program for antimicrobial drug consumption and resistance profiles, especially when developing standards of care tailored to meet an institution's needs.