|Year : 2017 | Volume
| Issue : 1 | Page : 10-17
Intensive care unit bugs in India: How do they differ from the western world?
Dhruva Chaudhry, Brijesh Prajapat
Department of Pulmonary and Critical Care Medicine, PGIMS, Rohtak, Haryana, India
|Date of Web Publication||29-Dec-2016|
Department of Pulmonary and Critical Care Medicine, PGIMS, Rohtak, Haryana
Source of Support: None, Conflict of Interest: None
Infections continue to play a significant role in the overall global mortality and disability more so in Intensive Care Units (ICUs) and plague developing countries more intensively. The ICUs are often called “the hubs” of infections owing to highly vulnerable patients’ profile. The most important nosocomial infections in the ICU are catheter-related bloodstream infections, ventilator-associated pneumonia, and catheter-associated urinary tract infections. The epidemiology of ICU infections in India is different from its Western counterparts in terms of prevalence and nature of microorganisms causing it. While Gram-positive infections are more prevalent in Western ICUs, Indian ICUs are commonly afflicted with Gram-negative bugs showing a high degree of antimicrobial resistance with blurring of traditional boundaries of early drug sensitive and later drug resistance infections. Increasing number of multidrug resistance organism infections in ICUs is a big public health threat and challenge both from the perspective of prevention and treatment. Therefore, blindly following the Western guidelines may not provide the optimum results in India. The need of the hour is to develop and implement an antimicrobial stewardship program based on the local epidemiological data and international guidelines to optimize the antimicrobial use among the hospitalized patients and improve their outcomes.
Keywords: Antibiotic stewardship, catheter‑associated urinary tract infections, catheter‑related blood stream infections, infection control, infections, multidrug resistance, ventilator‑associated pneumonias
|How to cite this article:|
Chaudhry D, Prajapat B. Intensive care unit bugs in India: How do they differ from the western world?. J Assoc Chest Physicians 2017;5:10-7
| Introduction|| |
Infections are among the most important causes of mortality worldwide and has plagued the low and lower-middle countries more intensely. Although the overall global mortality has decreased in the last three decades due to infections, it is still the most important cause of disability, and India is no exception which shows the same trends. The intensive care units (ICUs) are often called “the hubs” of infections. Extremely vulnerable population group with reduced host defenses and dysregulated immune responses, multiple procedures, and use of invasive devices such as endotracheal intubation, central venous cannulations, mechanical ventilation (MV), and urinary catheterizations distorting the anatomical integrity-protective barriers of patients are the important reasons. Both primary infections (at the time of admission) and secondary infections (occur during the stay in ICU or ICU-acquired infections) rates are high in ICUs. In fact, ICU population has one of the highest occurrence rates of nosocomial infections (20–30% of all ICU-admissions),, leading to an enormous impact on morbidity, hospital costs, and often survival., Both extended prevalence of infection in intensive care-1 (EPIC) and EPIC-2 studies clearly showed a high prevalence of infections in ICUs with EPIC-2 moved further and provided data and patterns of infections around the world including India. The study which was 1-day prospective point-prevalence study in 1265 participating ICUs (75 countries worldwide) showed that 51% of the 12,796 patients were infected.
Microbes are the organisms carrying the flag of infection, highly evolutionized species, and seriously at winning edge because of the weak arsenal of antibiotics, and limited and almost exhausted armamentarium against these organisms. The burden of “multidrug” antimicrobial resistance (MDR) in ICUs further escalates this problem. Thus, it is apt to describe the ICUs as factories for creating, disseminating, and amplifying antimicrobial resistance. Both infection and MDR results in a considerable clinical and economic burden and the presence of MDR boosts the deleterious impact of nosocomial infection. Compared with infections not caused by MDR microorganisms, the additional cost of multidrug resistance in hospitalized patients with infections has been estimated at $6000–$30,000 per patient. Several studies show that Western ICUs have more Gram-positive organisms causing infections as compared to Asian ICUs including India, where Gram-negative infections are predominant. However, in Western ICUs too, Gram-negative infections are on rise. Due to lack of local data from India, Western guidelines on initial antibiotic selection are generally used as surrogates for Indian ICUs and the empiric choice made for serious ICU-related infections. However, this practice may not provide the optimum results in India mainly due to varied prevalence of microbes in ICU and multidrug-resistant organisms (MDROs) across and within countries.,
| Epidemiology of Intensive Care Unit Infections - How are We Different from Western World?|| |
The global scenario shows that Gram-positive infections are more prevalent in the Western world ICUs, namely, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), penicillin-resistant Pneumococcus, Clostridium difficile colitis, etc., However, Gram-negative bugs dominate in India and Asia-Pacific region, namely, extended spectrum beta-lactamase (ESBLs), AmpCs, and carbapenemases. There occur variations within the country too, i.e., state to state, urban versus rural, health care versus community, government versus corporate/private hospitals, primary, secondary, and tertiary care hospitals. Local variations occur within a locality, community, different hospitals of a city, different wards of a hospital (ICU vs. general wards; and different ICUs such as surgical ICU, cardiac ICU, medical ICU, neonatal ICU, etc.) have different infections and bugs or microbes. The most important nosocomial infections in the ICU are catheter-related bloodstream infections (CRBSIs), ventilator-associated pneumonia (VAP), and catheter-associated urinary tract infections (CAUTIs). A large number of studies show CAUTIs as the most common nosocomial infection in ICUs.,,, However, other studies put VAP on the top of list.,,,,
The epic-2 study showed that lungs were the most common site of infection, accounting for 64% of infections, followed by abdominal (19%) and bloodstream (15%) infections. About 70%of infected patients had positive microbial isolates 47% of infections were associated with Gram-positive isolates, and 62% with Gram-negative isolates [Table 1]. In patients with positive isolates, the most commongram-positive organism was S. aureus (20%), and the most common Gram-negative organisms were Pseudomonas species (20%) and Escherichia More Details coli (16%) [Table 2]. There was considerable variation in the types of organisms isolated among the different geographical regions, for example, in Africa, 21% of positive isolates were MRSA, while in Western Europe and Oceania, the percentage was only 9. The proportion of Gram-negative organisms was much greater in Asia, Western Europe, and Latin America than in North America, Europe, or Oceania. In Asian ICUs, Gram-negative isolates constituted 75% as compared to 58% in Western Europe while Gram-positive isolates constituted 33% in Asian ICUs and 49.9% in Western Europe. EPIC-2 study results are somewhat different from the SOAP study group which reported an equal frequency of Gram-positive and -negative organisms. The difference is probably due to the inclusion of Asian, South American, and African ICUs in the EPIC-2 study while the latter included only European ICUs [Table 1].
|Table 1: Prevalence of microbiologic isolates from Intensive Care Units of different parts of world as depicted by extended prevalence of infection in intensive care 2 and soap study|
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|Table 2: Types of organisms in culture-positive infected patients according to geographical region as found in extended prevalence of infection in intensive care 2 study|
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Studies from Indian ICUs have reported high prevalence of Gram-negative bacterial infections such as with Acinetobacter baumannii, extended spectrum beta-lactamase, and metallo-beta-lactamase producing organisms (e.g., E. coli, Klebsiella pneumoniae) and drug-resistant Gram-positive organisms (MRSA, VRE, and others).,,, Recent reports of multidrug-resistant Gram-negative organisms in India have generated considerable scientific interest as well as concern and public health response., In a study from a tertiary care center ICU from North India, bacteriological culture came positive in 28% of enrolled patients. Gram-negative Bacteria were the most common and included A. baumanii (20.9%), K. pneumoniae (19.7%), E. coli (18.3%), and Pseudomonas aeruginosa (14.0%). Gram-positive infections included S. aureus (8.2%) and Enterococcus species (5.0%). Respiratory tract isolates were the most common (44.5%) followed by bloodstream (23.3%), urinary tract (16.1%), skin/soft tissue (9.1%), and intraabdominal (4.3%). A retrospective study of bacterial isolates from different ICUs of a tertiary care center from Rural Northern India too showed the preponderance of Gram-negative organisms and the frequently isolated Bacteria were P. aeruginosa (38.17%), K. pneumoniae (23.76%), followed by Acinetobacter anitratus (14.96%), Enterobacter (6%), and E. coli (6%). Gram-positive organisms (S. aureus - 2%, coagulase negative staphylococci [CoNS] - 2%, Enterococcus - 0.6%) constituted a small fraction. A study on Acinetobacter infections in a tertiary level ICU in Northern India showed that such infections are highly prevalent in the ICU, with patients being more susceptible to lung infection. Similarly, studies on nosocomial pathogens in ICU in Western India showed that major infections found in ICU were due to A. baumannii, E. coli, K. pneumoniae, P. aeruginosa, S. aureus, and Streptococcus spp., Dasgupta et al. from West India, Datta et al. from North India, Mythri and Kashinath from South India, and Choudhuri from East India showed that major ICU infections are caused by Gram-negative organisms [Table 3] and [Table 4]. INDICAPS study which is a multicenter, all India observational 4-day point prevalence study of infections in ICUs, acquired data of 124 ICUs, and over 4000 patients. The study found positive microbiological isolate in 1455 (36%) patients. Overall, 1077 organisms were identified of which 68.9% were Gram-negative organisms, 15.9% were Gram-positive organisms, and 7.5% were Fungi. It is a clear reflection that the Indian ICUs are plagued with Gram-negative bugs.
|Table 3: Prevalence of microbiologic isolates in Intensive Care Units from different areas of India|
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|Table 4: Types of organisms in culture-positive isolates from patients in Intensive Care Units from different areas of India|
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| Specific Nosocomial Infections in Intensive Care Unit|| |
VAP is a hospital-acquired infection seen among critically ill patients on MV due to various causes in ICUs. VAP occurs 48 h or more after endotracheal intubation and MV that was not incubating at the time of admission and also includes pneumonia developing after extubation. VAP increases morbidity, mortality as well as the cost of healthcare. Around 10–20% of patients on MV for longer than 48 h develop VAP. VAP is traditionally differentiated into early onset and late onset. Early-onset VAP, which occurs during the first 4 days of MV, is usually less severe, associated with a better prognosis, and more likely caused by antibiotic-sensitive Bacteria. Late onset VAP, which develops 5 or more days after initiation of MV, is caused by MDR pathogens and associated with increased mortality and morbidity and guidelines recommend monotherapy with narrow-spectrum antibiotics for early-onset infections and broad-spectrum therapy for late-onset infections. Studies from west have shown Gram-positive cocci mainly S. aureus mainly methicillin sensitive and Streptococcus pneumonia as the most frequently isolated organism in early onset VAP and Gram-negative Bacilli, MRSA as the most common etiological agents of late onset VAP.
The incidence of VAP in Indian ICUs is ranged from 30% to 73%.,,,, Early VAP ranges from 40% to 45%, and the majority are late VAP (55–60%).,,, However, unlike Western data, Gram-negative organisms are the most common etiological agents in both early and late VAP, most common being Pseudomonas, E. coli, and Acinetobacter.,, Among the isolated Gram-negative organisms, a significant number of VAP cases are due to nonfermenter which are often MDR strains. Ranjan et al. in their study of VAP in a tertiary hospital showed that the majority, i.e., 95.7% of bacterial isolates were Gram-negative Bacilli out of which Acinetobacter spp. accounted for 34.28% of VAP cases followed by P. aeruginosa (25.7%). Author’s experience and the data of the VAP patients from the author’s center which is a tertiary care center reflect the same trends. The bacteriological profiles of early VAP are clearly different from the western world where Gram-positive organisms are commonly seen., However, organisms isolated from late VAP in studies from Indian ICUs and Western ICUs are similar and predominantly Gram-negative organisms with MDR strains. Thus, the differentiation of VAP into early and late with regards to implicated organisms seems to be blurred in Indian ICUs. Most of the Enterobacteriaceae are ESBLs producers. Carbapenem resistance is also high with studies showing up to 40% of the Pseudomonas, and 37.5% of Acinetobacter species are MDR, even to carbapenems., Moreover, increased number of cases MRSA both in early and late VAP is also seen. Thus, the overall picture suggests that number of drug-resistant strains of various organisms is rising and is an important cause of VAP in Indian setting.
The frequency of specific MDR pathogens causing VAP may vary by hospital, patient population, and exposure to antibiotics, type of ICU patients and changes over time, emphasizing the need for timely local surveillance data. Knowledge of the susceptibility pattern of the local pathogens should guide the choice of antibiotics, in addition to the likelihood of organisms as there is an increasing prevalence of MDR pathogens in late onset VAP. On the basis of the cultured organisms and antibiotic susceptibility tests of several Indian studies, empirical therapy should be broadened to include either an antipseudomonal cephalosporin, a carbapenem, or a beta-lactam/beta-lactamase inhibitor plus an antipseudomonal fluoroquinolone, or an aminoglycoside plus linezolid or vancomycin to cover the most probable pathogens.
Catheter-related blood stream infections
CRBSIs are an important cause of morbidity and mortality worldwide. The incidence of CRBSI associated with central lines among patients hospitalized in ICUs in the USA decreased from 3.64 to 1.65 infections per 1000 central line days between 2001 and 2009. A similar trend of decreasing incidence has been observed in Canada. In comparison, the reported pooled incidence of central line–associated BSI across 422 ICUs in 36 countries in Latin America, Asia, Africa, and Europe from 2004 to 2009 was substantially higher, 6.8 events per 1000 central line days. Many of these sites are in resource-limited areas, and the high incidence is thought to be related to a lack of official regulations regarding catheter care. India is no exception and the study by Parameswaran et al. from a tertiary care center in South India shows the incidence of CRBSI as 8.75/1000 catheter days.
In a prospective analysis from the Surveillance and Control of Pathogens of Epidemiologic Importance database which included 24,179 nosocomial bloodstream infections occurring in 49 hospitals in the USA between 1995 and 2002, showed CoNS (31%), S. aureus (20%), enterococci (9%), Candida species (9%), E. coli (6%), Klebsiella species (5%), Pseudomonas species (4%), Enterobacter species (4%), Serratia species (2%), and A. baumannii (1%). Gram-positive isolates constituted 60% while Gram-negative isolates were around 20%. Indian scenario is somewhat different from the west with inclination toward Gram-negative organisms. While CoNS and Staphylococcus species are common Gram-positive microorganisms associated with CRBSI, Gram-negative isolates including Klebsiella sp., Enterobacter sp., and E. coli seems to be predominating in an Indian population with CRBSI over the last decade. Krishnan and Sureshkumar found in his study that Gram-positive cocci constituted 27% of isolates, and Gram-negative Bacilli were 56%. The proportion of Gram-negative CRBSI is much higher than that reported in Western hospitals with Gram-negative organisms showing more and frequent resistance patterns than the Gram-positive organisms. Datta et al. and Kaur et al. supported and showed the same trend of Gram-negative organisms being the most common isolates in CRBSI. However, study by Parameswaran et al. at a tertiary care center in South India and Patil et al. found that Gram-positive organisms were more frequently isolated (65%) than Gram-negative organisms with ConS being the most common organisms. The occurrence of candidemia as a nosocomial bloodstream infection has been increasing in India, and central venous catheters have been significantly related to the acquisition of candidemia. Fungi isolates causing CRBSI is around 5–15% in various studies.,,
Cather-associated urinary tract infection
CAUTI is an important cause of morbidity and mortality in Indian subjects, affecting all age groups. Bacteriuria or candiduria is almost inevitable in nearly half of the patients who require an indwelling urinary catheter for more than 5 days. Asymptomatic bacteriuria constitutes a major pool of the antibiotic-resistant strains of pathogens in any hospital, with critical care units (CCUs) accounting for the majority of them. CAUTI is also a major cause of hospital-acquired bacteremia, and even asymptomatic bacteriuria may be associated with enhanced in-hospital mortality rates., The Centers for Disease Control and Prevention defines CAUTI for those patients who have an indwelling catheter in place for 48 h or more. Almost all microorganisms implicated in endemic CAUTI are either part of the patient, s colonic or perineal flora or derived from the hands of medical and paramedical personnel during the insertion of indwelling catheters or improper handling of the collection system. Datta et al. demonstrated the frequency of microorganisms implicated in CAUTI (Acinetobacter species - 9.5%, P. aeruginosa - 35.7%, Enterococcus species - 15.4%, K. pneumonia - 15.4%, E. coli - 10.7%, Candida species - 11.9%, Morganella morganii - 1.1%. Antimicrobial drug therapy while protective for short-duration catheterizations carries the risk of selective colonization with MDROs such as P. aeruginosa, other resistant Gram-negative Bacilli, enterococci, and yeasts leading to outbreaks of infections with these MDRO in ICUs. CCU-acquired CAUTI was not found to be an independent risk factor of in-hospital death, although it contributes to significant morbidity.
Antimicrobial resistance in Intensive Care Units - The dawn of superbugs!!
The emergence of MDR often is dedicated to the excessive use of broad-spectrum antimicrobial agents with more than 60% of all ICU patients receive antibiotics during their stay, but the epidemiology of MDR is much more complex and multifactorial in nature. Bonten and Mascini recognized four main forces behind the emergence and further spread of MDR microorganisms: (1) induction of resistant stains, (2) selection of resistant strains, (3) introduction of resistant strains, and (4) dissemination of resistant strains. A bacterium carrying several antibiotic-resistant genes is called multi-resistant Bacteria or casually, a “super Bacteria” or “super bug.” However, these should not be dealt in a casual manner as infections caused by them are difficult to treat. The infamous New Delhi metallo beta lactamase-1 created a havoc in 2010 and pulled a lot of scientific and public health response.
During the past decades, a global shift in the MDR dilemma has been noted from Gram-positive to Gram-negative Bacteria, especially due to the scarceness of new antimicrobial agents active against resistant Gram-negative microorganisms. According to EPIC-2 both MRSA and VRE, organisms are more prevalent in West as compared to Asian countries. In Gram-negative Bacteria, the resistance is mainly due to the rapid increase of ESBLs in K. pneumoniae, E. coli, and Proteus mirabilis; high-level third generation cephalosporin beta-lactamase resistance among Enterobacter spp. and Citrobacter spp., and MDR in P. aeruginosa, Acinetobacter spp., and Stenotrophomonas maltophilia. In 2007, already 79% of E. coli isolates collected in India were positive for ESBLs, with an almost identical prevalence in both hospital and community. Acinetobacter isolates in multiple medical ICUs in India have displayed high level of antibiotic resistance. The pharmacological sensitivity profile for common Bacteria such as Escherichia and Klebsiella reveal a disturbing trend. There is a high prevalence of resistance to common antibiotics, and carbapenem resistance is observed in more than 50% of Klebsiella isolates and in about 20% of E. coli isolates. The prevalence of various beta-lactamases in the Gram-negative Bacteria including the Enterobactericeae and the nonfermenters is 70.69%, which is alarmingly high and among beta-lactamases the prevalence of ESBL is much more as depicted by Oberoi et al. and Bandekar et al. It has been shown that the prevalence of the ESBLs among the clinical isolates varies from country to country and institution to institution within the same country. High prevalence of AmpC production is also a major threat. It prevalence is 17.3% in a study in Kolkata, and 22.9% in a study done by Bandekar et al., whereas a study which was done by Bhattacharjee et al. showed 22% AmpC producing P. aeruginosa. The coexistence of different classes of beta-lactamases in a single bacterial isolate may pose diagnostic and treatment challenges. The AmpC producing organisms can act as a hidden reservoir for the ESBLs. In addition, the high-level expression of the AmpC beta-lactamases may mask the recognition of the ESBLs and it may result in a fatal and an inappropriate antimicrobial therapy. The increase in the prevalence of the AmpC, MBL, and the ESBL producing isolates is just a beginning of the ominous trend of more and more isolates acquiring the resistance mechanisms, thus rendering the already weakened antimicrobial armamentarium ineffective.
| Conclusion|| |
Infections are among the most important causes of mortality worldwide. Although ICUs constitute only 4–5% beds strength of a hospital, they harbor up to 30% of the nosocomial infections in the hospital. The organisms or bugs causing ICUs infections are different in low- or middle-income countries like India as compared to developed Western world with more Gram-negative infections with MDROs in the former group. Inadequate infection control facilities in the hospitals, due to lack of resources, ignorance about the gravity of the situation or the obvious neglect to follow precautions even in resource-rich tertiary care centers, provide a perfect milieu and breeding ground for these superbugs. The need of the hour is that every health-care institution must develop its own antimicrobial stewardship program which should be based on the local epidemiological data and international guidelines, to optimize the antimicrobial use among the hospitalized patients, to improve the patient outcomes, to ensure a cost-effective therapy, and to reduce the adverse consequences of the antimicrobial use. Preventive measures such as a continuous surveillance of the ICUs and a strict implementation of infection control practices can go a long way in containing the threat of drug resistance in the health-care settings.
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[Table 1], [Table 2], [Table 3], [Table 4]