Prevalence, etiology, and antibiotic resistance profiles of bacterial bloodstream infections in a tertiary care hospital in Northern India: A 4-year study

Introduction

Bloodstream infections (BSIs) range from self-limiting infections to life-threatening sepsis and are an important cause of sepsis-related morbidity and mortality worldwide.[1] Studies have revealed that the annual numbers of BSI episodes ranged from 1,213,460 to 1,381,590 in Europe and 575.462–677.389 in North America with large annual numbers of BSI-associated deaths.[2] In a developed setting, the inhospital mortality rates are observed to be at least 40%.[3] Data on the profile of BSI from low- and middle-income countries like India are limited.[4]

The epidemiology and pathogen profile of BSIs vary between regions.[5] This considerable unevenness between hospitals and health-care centers in different countries requires constant analysis of local trends. Many bacterial pathogens have developed resistance to most of the antibiotics and are creating a serious health crisis with many economic and social inferences all over the worlds.[6]

The changing epidemiology and susceptibility patterns of microorganisms in India threaten the effectiveness of most, if not all; antibiotics frequently used to prevent and treat bacterial infections.[7] In addition to the increasing resistance to even the last resort drugs such as colistin from across the globe, the situation is getting graver because of the absence of any new drugs in the pipeline.[89]

There is a dearth of detailed studies and data on prevalence, etiology, and antibiotic resistance profiles of bacterial BSIs in India. Such data are crucial for enabling clinicians to improve the empirical treatment and administer appropriate antimicrobial therapy. In addition, it is vital to recognize and track the source of all BSIs to prioritize and implement preventive measures.

India is a developing economy and a hotspot for emerging infectious diseases. Rates of antibiotic resistance, an important reason of treatment failure and subsequent mortality are also alarming in India. However, the epidemiology of BSI in Indian adults is not well studied and thus requires constant surveillance of bloodstream infections.

With this background, the present study was conducted to analyze various organisms causing BSI and their prevalence and antibiotic resistance pattern, which would ultimately aid in decreasing the hospital stay and cost of treatment which would consequently reduce mortality. This article reports a 4-year retrospective analysis of BSI data at a tertiary referral center in India.

Materials and Methods

Results

Study population's demographics

After exclusion of blood cultures positive with contaminants, as per standard definitions, 1983 positive bacterial blood cultures were recorded between January 2013 and December 2016, from which a total of 2017 bacteria were isolated.

The median age of the patients varied from 30 to 35 years, with the percentage of females in the study population being 17%–19% [Table 1]. The range of patient-age largely lied between 24 and 54 years during the study. Among the 1983 positive blood samples 1009 (51%), 902 (45%), 17 (1%), 23 (1%), and 32 (2%), were recovered respectively from surgical Intensive Care Units (ICUs), neurosurgical ICUs, orthopedic ICUs, emergency department, and follow-up outpatients.

Table 1 Characteristics of the clinical study population

Analysis of microbiological dataset

During the 4-year study, a total of 1983 blood samples of BSI patients were received in the laboratory, and more than one bacterium were isolated from 1.5% (29/1983) of these blood samples. A total of 2017 bacterial isolates were identified with 82% (1646/2017) with Gram-negative bacteria isolated and 18% (371/2012) Gram-positive bacteria. Gram-negative bacteria were the most common cause of bloodstream infection in adults presenting to our tertiary referral hospital during all 4 years (78%–85%). Acinetobacter species was the most commonly isolated bacteria in 2013, 2015, and 2016. Enterobacteriaceae were the most commonly isolated group of organisms among the study cases in all the 4 years except for 2014, when 26% of the total isolated bacteria were Burkholderia spp. This was a part of an outbreak (under publication). The predominant Enterobacteriaceae was Klebsiella spp. throughout the study, followed by Escherichia coli and Serratia spp in 2013 and 2015 and 2014 and 2016 respectively. Nonenterobacteriaceae were observed to be 43%–58% of the total bacteria isolated during the study period. Among Gram-positive isolates, Staphylococcus species were the leading pathogen (11%–15%), followed by Enterococcus spp. (4%–7%) [Table 2].

Table 2 Etiology of bacterial bloodstream infections

Tables 3 and 4 display the rates of antibiotic resistance of Gram-negative and Gram-positive isolates. Very high levels of antibiotic resistance were seen across all genera of family Enterobacteriaceae which was found to be statistically significant for all the antimicrobials tested. Similar trends were observed among the nonEnterobacteriaceae [Table 3]. Discordant resistant profiles between disc diffusion and Vitek II were obtained with colistin (results not reported here). Statistically significant antibiotic resistance to amoxicillin-clavulanic acid (P < 0.000), ampicillin (P = 0.021), clindamycin (P = 0.035), co-trimoxazole (P = 0.005), gentamicin (P < 0.000), levofloxacin (P = 0.006), oxacillin (P < 0.000), penicillin (P = 0.001), and rifampicin (P = 0.001) was observed among Gram-positive bacteria [Table 4].

Table 3 Resistance among Gram-negative bacteria from bloodstream infections

Table 4 Resistance among Gram-positive bacteria from bloodstream infections

Discussion

Among all types of nosocomial infections, BSIs prove to be potentially the most grave and expensive. Patients admitted to ICUs have an even higher risk of nosocomial BSIs than those admitted to other types of units. Although the causative agents are affected by a number of factors; predominantly the focus of infection, comorbidities such as chronic diseased conditions, immunodeficiency, other than geographic, socioeconomic and environmental factors, important insights can be gained from the analyses of the microbiological profile of BSIs as most cases reflect severe illness and the bacteria detected are usually the causative agents of the disease. The unprecedented antimicrobial resistance to antimicrobials like colistin has breached one of the last lines of defense against such infections with multidrug-resistant bugs.[9] We observed a predominance of young and middle-aged adult males among patients with BSI (81%–83%). This phenomenon is similar to various studies reporting septic shock as one of the top causes of death.[4] We observed a higher proportion of males than females. The highest percentage of patients with BSI in our study were from surgical and neurosurgical ICUs.

In a previous study from the same center conducted in 2011–2012 a high prevalence of BSIs was reported. We reported a total of 316 organisms isolated from the 296 episodes of BSIs.[11] The numbers have only increased since then. Acinetobacter species followed by Klebsiella species are still the most common cause of BSI.

Gram-positive and Gram-negative bacteria showed very high resistance to most the antibiotics tested, and the statistical analysis clearly suggest that the drug resistance is undeniably significant and poses threat more-so to high-risk patients having blood culture positive.

Our study, however, has some important limitations. First, our trauma center is a tertiary referral hospital and specializes in trauma cases. Therefore, the pattern of etiology, resistance, and spectrum of clinical disease is different from that seen in other hospitals in India. Second, we have reported only the total number of organisms and not the BSI episodes. Study of BSI episodes classified into community- and hospital-acquired BSIs would have led to a more comprehensive analysis. Finally, the importance and role of certain bacteria, such as Aeromonas species or Stenotrophomonas species, which have been associated with both real and pseudobacteremia infection was not ascertained because of a lack of repeat sampling and the retrospective nature of our study.

Considering the load of BSI and the toll it is taking, especially on our young and middle-aged adult population, we are in dire need of rapid identification and antimicrobial susceptibility testing of the causative agents of bloodstream infections. Such point-of-care testing systems would promptly provide essential information to clinicians for selecting an appropriate antimicrobial therapy for patients with potentially fatal bloodstream infections. We have seen a positive impact of an intensive surveillance on the central line-associated bloodstream infections in a study conducted at our center emphasizing the need of regular and stringent surveillance of BSI.[12] Thus, a deeper understanding of the prevalence, etiology of BSIs in India, its resistance patterns and their impact on patients’ outcomes is important to guide clinical management and appropriate antibiotic use.

Conclusion

We require a detailed analysis of the prevalence and etiology of BSIs and its resistance profile. It will lead to appropriate antibiotic use, clinical management, and formulation of antibiotic policies and preventive measures.