RECENT INCREASE IN COLISTIN-RESISTANT EXTENSIVELY DRUG RESISTANT ACINETOBACTER INFECTIONS AT A TERTIARY CARE CENTER IN PAKISTAN

Acinetobacter is an important nosocomial pathogen and a major cause of morbidity and mortality in hospitalized patients. Recently, colistin resistant strains of Acinetobacter were reported from different parts of the world. We are describing a case series of 18 patients with colistin resistant Acinetobacter over a span of 4 years. Patients with any clinical specimen positive for colistin resistant Acinetobacter from 2014 to 2017 were identified from the hospital records. Three cases were isolated between 2014 and 2015, six cases in 2016 and 9 cases in 2017. Data on patients’ demographics as well as clinical data was collected retrospectively on a structured proforma from the hospital medical records.

Infections due to Colistin resistant strains of Acinetobacter are rapidly increasing, have limited antimicrobial treatment options and are associated with poor outcomes.

BACKGROUND
Acinetobacter is an important nosocomial pathogen and a major cause of morbidity and mortality in hospitalized patients (1). It causes hospital-acquired pneumonia, central line associated bloodstream infections as well as surgical site infections (2).
Infections caused by Acinetobacter sp. are especially difficult to treat due to increasing carbapenem resistance and surveillance studies have shown that the percentage of carbapenem-resistant isolates have gradually increased over the last ten years in Europe, North America, South Asia and Latin America (3). Hence it was included among the six ESKAPE organisms responsible for causing difficult to treat nosocomial infections by the Infectious Diseases Society of America (4).
Increasingly worrisome are reports of emergence of colistin resistant Acinetobacter species. Colistin is usually considered an antibiotic of last resort against multidrug resistant gram negative organisms (5). However, in a surveillance study from US, colistin resistance was reported in approximately 5% of all Acinetobacter strains (6).
This has been attributed to prior colistin use (7). However data is still sparse regarding other predisposing factors. There are also no standard guidelines for treatment but several studies recommend combination therapies such as colistin in combination with carbapenem or sulbactam in multi-drug resistant, carbapenem resistant Acinetobacter infections (8,9). It is still unclear as to which treatment regimen is optimal for use in patients infected with colistin resistant Acinetobacter species as well as the clinical course and prognosis of these patients. Therefore, in this study, we aim to share our experience of managing infections due to colistin resistant Acinetobacter species over a period of 4 years at a tertiary care hospital in Pakistan. In addition to colistin resistance, carbapenem and amikacin resistance was documented to be 94% and 61% respectively. All isolates were non-susceptible to piperacillin tazobactam, 83% were non-susceptible to trimethoprimsulfamethoxazole. Out of nine specimens which were checked for minocycline susceptibility, only one was non-susceptible. Tigecycline susceptibility was available for six cases and none were sensitive. One of the isolates was resistant to all drugs except minocycline. Drug susceptibilities are shown in Figure 1. The treatment options for this organism are limited and include combination therapy with 3 to 4 drug regimen (8). We observed a higher mortality rate of 44% during hospital stay as compared to 30-day mortality rate of 30% in the case series from US (7). Two thirds of our cases required ICU stay compared to 62% in a study from Greece (12). Pneumonia was seen in 72% of our cases which was similar to the US study (7) though the study from Greece reported pneumonia in 42% with bloodstream infections being the most common in their center (12). There was no difference in mortality despite including a drug to which the organism was sensitive on culture as compared to other case series where combination treatment with carbapenem, colistimethate sodium and ampicillin sulbactam was associated with better outcome (7). The antimicrobial susceptibility was similar to the case series reported from US except for amikacin which was non-susceptible in 61% in our study compared to 94 % (7). In our study, 8 out of 9 specimens in which minocycline susceptibility was checked were found to be sensitive to this drug. Previous studies do indicate a potential role of minocycline in combination with colistin for MDR Acinetobacter; however data on the use of this combination is limited (13).

METHODS
To the best of our knowledge, this is the first case series from South Asia describing clinical characteristics of patients with colistin resistant Acinetobacter infections.
However, we do not have molecular typing for our isolates although we do have data from our center where isolates were all positive for Bla OxA-51-like , hence identified as A. baumannii. Same study also reported Bla OxA-23-like acquired carbapenemase gene in the majority of Carbapenem resistant strains of Acinetobacter (14). Our study has limited generalizability as it is from a single center. However, it highlights the urgency and importance of data from this region.   Figure 1 Antimicrobial susceptibility pattern of Acinetobacter species