ORIGINAL ARTICLE |
https://doi.org/10.5005/jp-journals-10081-1458 |
Profile of Positive Cultures in Pediatric Intensive Care Unit: A Retrospective Cohort Study
1,2,4,5Department of Pediatric Intensive Care Unit, Bai Jerbai Wadia Hospital for Children, Mumbai, Maharashtra, India
3Department of Microbiology and Infection Control, Bai Jerbai Wadia Hospital for Children, Mumbai, Maharashtra, India
Corresponding Author: Rekha Solomon, Department of Pediatric Intensive Care Unit, Bai Jerbai Wadia Hospital for Children, Mumbai, Maharashtra, India, Phone: +91 9820957669, e-mail: rekhasolomon1@gmail.com
Received: 10 September 2024; Accepted: 08 December 2024; Published on: 20 March 2025
ABSTRACT
Infections are an important cause of morbidity and mortality in the pediatric intensive care unit (PICU).
Aims and objectives: To study the demographic profile, describe the spectrum and resistance pattern of organisms isolated from blood and respiratory cultures, and study the outcome.
Materials and methods: This retrospective observational study, conducted from January 1 to December 31, 2021, was performed on children with positive blood and respiratory cultures admitted to the PICU of a tertiary care multispecialty hospital. Demographic profile and outcome measures were recorded. Positive cultures and resistance patterns were noted.
Results: There were 139 children with positive cultures, with a median age of 12 months. The majority of children had comorbidities (62.6%), previous hospital admissions (83.5%), and/or antibiotic exposure (85.4%). Gram-negative bacilli (GNB) comprised 99% of positive respiratory cultures in hospital-acquired infections (HAI), and the most common organisms grown were Acinetobacter species, Klebsiella species, and Pseudomonas species. On antibiotic sensitivity testing, approximately three-fourths of the organisms showed multidrug resistance. High levels of carbapenem resistance were seen in isolates of Acinetobacter baumannii (40/48), Klebsiella pneumoniae (25/29), and Pseudomonas aeruginosa (22/37). Out of the 139 patients included in the study, 86 (61.9%) survived. On multivariate analysis, multidrug resistant organisms (MDRO) were significantly associated with mortality (p = 0.02).
Conclusion: Infections in critically ill children were predominantly due to gram-negative organisms. There is a trend toward increasing antibiotic resistance over time. Infection with MDRO is associated with mortality.
Highlights: Infections represent a major burden in developing countries, especially in critically ill children. Our study shows high levels of multidrug resistance and increasing carbapenem resistance over time. We have demonstrated a higher risk of mortality in children with MDRO.
Keywords: Antibiotic resistance, Culture positive inflection, Multidrug resistant organism, Pediatric intensive care unit
How to cite this article: Bhagat I, Solomon R, Mamtora D, et al. Profile of Positive Cultures in Pediatric Intensive Care Unit: A Retrospective Cohort Study. Pediatr Inf Dis 2025;7(2):44–49.
Source of support: Nil
Conflict of interest: None
INTRODUCTION
Infectious diseases continue to be the leading cause of mortality in children in developing countries. In addition, the burden of healthcare-associated infections, which are often multidrug-resistant, adds to the morbidity and mortality in the Pediatric Intensive Care Unit (PICU). ICUs in lower-middle-income countries (LMIC) are suspected to pose a special risk for patients acquiring infections due to multidrug resistant organisms (MDRO). Unfortunately, there are relatively few studies published from LMICs on this topic, especially in the pediatric population. There is, thus, a great unmet need in most LMICs to perform surveillance of infections and antimicrobial susceptibility patterns.
Antimicrobial resistance (AMR) is a global threat to society, with deaths attributed to resistant infections projected to exceed 10 million per year by 2050. India is one of the biggest consumers of antibiotics globally, with 10.7 units/person annually, the rate being highest in children between 0 and 4 years of age.1,3 The critically ill patient admitted to the PICU with sepsis may have acquired the infection from the community, ward, or other referral hospitals, and this should be borne in mind while selecting the initial empiric antibiotic therapy in patients with sepsis and septic shock. In the PICU, especially in septic shock patients, it is very crucial to choose the right antibiotic with little room for error, making it essential to monitor the antibiogram periodically.
Aims and Objectives
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To study the demographic profile and outcome of critically ill children with positive blood or respiratory culture.
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To describe the spectrum and resistance pattern of the above positive blood and respiratory cultures.
MATERIALS AND METHODS
This retrospective observational cohort study was conducted on children aged 1 month to 18 years, with positive blood and respiratory cultures, admitted to the PICU at a tertiary care multispecialty pediatric hospital from January 1 to December 31, 2021. Institutional Ethics Committee approval with a waiver of consent was obtained (IEC-BJWHC/AP/2024/012).
Blood samples and respiratory secretions [endotracheal (ET), bronchoscopic, and nonbronchoscopic alveolar lavage (N-BAL)] were taken on PICU admission and/or during the stay based on clinical indications at the discretion of the treating physician. Blood cultures were done using the automated BACTEC® FX-40 system (Becton Dickinson, USA)/microbial detection system and incubated for 5 (bacterial) to 14 days (fungal culture). Positive blood culture bottles and other isolated samples were initially grown on MacConkey, sheep blood agar, or Sabouraud dextrose agar (SDA) for 24–48 hours at 37°C. Susceptibility of antimicrobial agents was tested on Vitek 2 susceptibility cards provided by the manufacturer (Vitek2 automated bacterial identification and antibiogram system, Biomerieux, France) or by the Kirby–Bauer disk diffusion or E strip method. Results were interpreted according to the Clinical and Laboratory Standards Institute (CLSI) 2020 criteria and were categorized as sensitive (S), intermediate (I), or resistant (R).4
Patients with signs and symptoms of infection with (1) positive culture of ET secretions >105 colony count or N-BAL >104 colony count, or bronchoalveolar lavage (BAL) >104 colony count, and/or (2) positive blood culture with a known pathogen or at least two positive blood cultures with a commensal or suspected contaminant were included in the study.
The following patients were excluded: those with a single isolate of coagulase-negative staphylococcus (CoNS) or other skin commensals in blood culture, respiratory specimen culture with growth of three or more organisms, and culture of Candida from ET or BAL secretions.
Positive blood culture isolates were recorded as admission cultures and likely community-acquired if detected from cultures sent within 48 hours of admission, and hospital-acquired isolates if the culture was sent after 48 hours in our hospital or another healthcare facility. Hospital-acquired respiratory infections are defined as respiratory infections in a child on invasive mechanical ventilation or high-frequency oscillatory ventilation for >48 hours.5 MDRO were defined as acquired resistance to at least one agent in three or more antimicrobial categories.6
The total number of cultures sent, the number of positive cultures in different specimens, nonduplicate organisms detected, antibiotic sensitivity and resistance patterns were noted, and the antibiotic resistance was compared with the unit antibiogram of 2015 and 2018 from prior audits.
Demographic data including age, sex, comorbidities, immune deficiency or suppression, previous hospital exposure, prior antibiotic therapy, primary system involved, and need for invasive lines and/or mechanical ventilation were recorded. Outcome measures such as duration of mechanical ventilation, length of PICU stay, and mortality were recorded.
Statistics
Sample Size Calculation
Based on previous hospital records, approximately 2,500 samples of blood and respiratory secretions are sent for culture sensitivity testing per year from the PICU. Based on previous studies, the overall prevalence of culture positivity is 12%.7 Considering a 12% prevalence, a total of 158 samples would have to be sent to achieve a 95% confidence level of ±5% around a 12% prevalence of culture positivity.
Categorical data were displayed as percentages. Numeric data were shown as the mean if normally distributed and as the median if not normally distributed. The study of factors affecting mortality was done using the Pearson Chi-squared test for categorical data. The Mann–Whitney U test was used for numeric data that were not normally distributed. Logistic regression analysis was used to study the association between variables. Comparison of outcome mortality between MDRO and non-MDRO infections was done using the Chi-squared test.
RESULTS
During this time period, there were 1,481 admissions in the PICU, of which 139 patients fulfilled the inclusion criteria. Of a total of 2,210 blood cultures, 94 were positive, with a positivity rate of 4.2%. Out of 628 respiratory specimens, 125 organisms were isolated from 112 specimens (ET secretions-93, BAL-16, N-BAL-3), with a positivity rate of 17.8%.
The majority of patients with positive cultures were below 1 year of age (56%). The median age was 12 months (1 month to 16 years), and 64.7% were males (Table 1). The respiratory system was primarily involved in the majority of patients (41%), followed by cardiovascular and hematology/oncology diagnoses. Preexisting comorbidity was present in 87 (62.6%) patients. The majority of patients had prior antibiotic exposure (n = 116; 83.5%) and prior hospital exposure (n = 119; 85.6%). An invasive device (ET, central line, arterial line) was present in up to 122 (87.2%) patients. Primary or secondary immunodeficiency was present in 29 (20.9%) patients.
| Number, n = 139 (%) | |
|---|---|
| Age in months: 0–6 6–12 13–60 >60 |
47 (33.8%) 32 (23%) 34 (24.5%) 26 (18.7%) |
| Sex: male | 90 (64.7%) |
| Primary system: Respiratory Cardiovascular Renal CNS GI Hemato-onco Other |
57 (41%) 18 (12.9%) 7 (5%) 17 (12.2%) 12 (8.6%) 18 (12.9%) 10 (7.2%) |
| Comorbidity None |
87 (62.6%) 52 (37.4%) |
| Previous antimicrobial exposure | 116 (83.5%) |
| Prior hospital exposure | 119 (85.6%) |
| Central venous catheter | 117 (84.2%) |
| Invasive mechanical ventilation | 122 (87.8%) |
| Arterial line | 66 (47.5%) |
| Immune deficiency/immune suppression | 29 (20.9%) |
Of all the isolates as admission respiratory infections, the majority (12/15) were gram-negative organisms, such as Escherichia coli (n = 4), Klebsiella pneumoniae (n = 3), Pseudomonas (n = 3), Elizabethkingia meningoseptica, and Enterobacter. Only three isolates were gram-positive (Streptococcus pneumoniae).
Among 19 culture-positive community-acquired bloodstream infections (BSI), gram-positive infections (8/19) and gram-negative infections (10/19) were almost equal, and one isolate was Candida tropicalis. The isolated gram-positive cultures included Staphylococcus (3), Enterococcus faecium (2), S. pneumoniae (2), and Streptococcus species (1).
There were 110 culture-positive hospital-acquired respiratory infections. Of these positive cultures, 109/110 were gram-negative organisms, and only 1 was gram-positive. Of the gram-negative organisms, Acinetobacter baumannii (33%) was the commonest, followed by Pseudomonas aeruginosa (25%), K. pneumoniae (18%), Elizabethkingia meningoseptica (10%), Burkholderia cepacia (5.6%), E. coli (3.6%), Enterobacter cloacae (1.8%), and Stenotrophomonas maltophila (0.9%). There was 1 isolate of Staphylococcus aureus.
Among hospital-acquired blood infections, three-quarters (56/75, 75%) were gram-negative bacterial infections, followed by fungal infections (15/75, 20%), and only four isolates showed gram-positive organisms (Enterococcus and methicillin-resistant CoNS). Apart from commonly reported hospital-acquired gram-negative infections like A. baumannii (12/75, 16%), P. aeruginosa (9/75, 12%), K. pneumoniae (9/75, 12%), and E. coli (2/75, 2.7%), other organisms such as Elizabethkingia meningoseptica (9/75, 12%), S. maltophila (6/75, 8%), B. cepacia (3/75, 4%), Serratia marcescens (2/75, 2.7%), Chryseobacterium indologenes (1/75), and Achromobacter xylosidans (1/75) were seen.
Of the positive HAI fungal blood cultures, the majority (11/16) were nonalbicans, that is, Candida parapsilosis (4/16), Candida auris (4/16), C. tropicalis (2/16), and Candida dubliniensis (1/16). There was only one isolate of Candida albicans, and species could not be identified in four isolates.
The resistance pattern of the hospital-acquired respiratory and BSI pathogens is shown in Table 2. There was a high prevalence of resistance of gram-negative bacilli (GNB) from respiratory secretions as well as blood to cephalosporins, carbapenems, and aminoglycosides. More than 80% of the isolates of A. baumannii showed resistance to cephalosporins, beta-lactam inhibitors, fluoroquinolones, aminoglycosides, trimethoprim-sulfamethoxazole, and carbapenems.
| A. baumanii (n = 48) |
P. aeroginosa (n = 37) |
K. pneumoniae (n = 29) |
Elizabethkingae meningosepticum (n = 20) |
B. cepacia (n = 10) |
S. maltophila (n = 7) |
E. coli (n = 6) | |
|---|---|---|---|---|---|---|---|
| Cephalosporin | 40 | 23 | 25 | 19 | 5 | 2 | 4 |
| Piperacillin-tazobactam | 38 | 20 | 25 | 20 | 10 | 7 | 4 |
| Any carbepenem | 40 | 22 | 25 | 20 | 10 | 7 | 3 |
| Aminoglycoside | 39 | 19 | 21 | 20 | 10 | 7 | 2 |
| Fluoroquinolone | 38 | 20 | 23 | 19 | 3 | 0 | 4 |
| Trimethoprim-sulfamethoxazole | 37 | 22 | 20 | 3 | 2 | 0 | 3 |
| Colistin | 1 | 0 | 0 | 20 | 10 | 7 | 0 |
| Minocycline | 0/15 | – | – | 0/14 | 1/4 |
Similarly, >50% of isolates of Pseudomonas were resistant to cephalosporins, beta-lactam inhibitors, fluoroquinolones, aminoglycosides, trimethoprim-sulfamethoxazole, and carbapenems. More than two-thirds of isolates of K. pneumoniae were resistant to the above antibiotics.
There were 10 children with a positive culture for S. maltophila: two community-acquired and eight hospital-acquired. Of the seven positive blood culture isolates, all were susceptible to fluoroquinolones, trimethoprim-sulfamethoxazole, and minocycline, and resistant to beta-lactams, aminoglycosides, and colistin.
There were 19 isolates of Elizabethkingia meningoseptica (10 in respiratory secretions, 9 in blood), of which most isolates (17/19, 89%) were sensitive to Septran, and all were resistant to cephalosporins and aminoglycosides. Of eight isolates tested for sensitivity to minocycline, all were sensitive.
Resistance to fluconazole was seen in more than three-quarters (13/16) of isolates of Candida, while resistance to amphotericin as well as to voriconazole was seen in seven isolates. Resistance to echinocandins (micafungin and caspofungin) was seen in an isolate of C. auris.
Infection with MDRO was seen in 107 children. There were 46 children with multiple nonduplicated infections. The median duration of mechanical ventilation was 10 days (IQR 1, 55), and the median length of stay was 11 days (IQR 1, 58). Out of the 139 patients included in the study, 86 (61.9%) survived (Table 3).
| Number, n = 139 (%) | |
|---|---|
| Infection with MDRO | 107 (77%) |
| Multiple isolates positive | 46 (33.1%) |
| Length of stay (median, IQR) | 11 (1,58) |
| Duration of mechanical ventilation (n = 122; median, IQR) | 10 (1,55) |
| Survived (%) | 86 (61.9%) |
On univariate analysis, previous hospitalization (odds ratio 4.14, 95% confidence interval 1.14–14.77), multiple infections (OR 2.41, 95% CI 1.17–4.98), previous antibiotic exposure (OR 5.05, 95% CI 1.45–17.95), and MDRO (OR 5.91, 95% CI 1.95–18.03) were significantly associated with mortality; there was no association of age, gender, focus of infection, immune deficiency, or comorbidity with mortality.
On multivariate logistic regression analysis, only infection with MDRO was significantly associated with mortality (p = 0.02); age, gender, comorbidity, previous hospitalization, previous antibiotic exposure, immune deficiency, and multiple infections were not associated with mortality.
The antibiogram of A. baumannii, Pseudomonas, and Enterobacteriaceae from blood to respiratory secretions was compared to previous years. Carbapenem-resistant A. baumannii has progressively increased from 30% in 2015 to 60% in 2018, now to 83% (43/48) in 2021 (Table 4). Resistance of Pseudomonas to carbapenems has doubled from 30% to nearly 60%. Resistance of the tested antibiotics progressively increased, with carbapenem resistance of Enterobacteriaceae rising 1.5 times from 50 to 75%. Resistance of Acinetobacter to extended-spectrum beta-lactams, fluoroquinolones, and aminoglycosides remained high at >70% (Fig. 1).
| 2015 | 2018 | 2021 | |
|---|---|---|---|
| A. baumanii | 30 | 60 | 82 |
| P. aeruginosa | 30 | 45 | 59 |
| Enterobacteriaceae | 50 | 65 | 77 |
Fig. 1: Resistance pattern (%) of A. Baumanii infection (blood and respiratory) over three time periods
DISCUSSION
Antibiotic stewardship programs (ASPs) are widely encouraged to prescribe antibiotics rationally and prevent the development of resistance. A primary tenet of ASPs is the establishment of empiric antibiotic recommendations for commonly acquired infections. An important tool in providing empiric antibiotic recommendations is the use of an antibiogram, which provides a snapshot of an institution’s pathogens and susceptibility profile. Hence, this study was undertaken to determine the microbial pattern in our region.
The demographic parameters of our study reveal that the number of males admitted to the PICU is more than double that of females. The median age of our patients was 1 year (IQR 0.1, 16). The majority of patients were admitted with respiratory illnesses, followed by cardiac, hematology-oncology, and neurological diagnoses. Ours is a tertiary care referral hospital for western India with well-established pediatric subspecialties, including pediatric oncology, neurology, nephrology, immunology, cardiac surgery, liver and renal transplant, and hematopoietic stem cell transplant. Thus, the majority of our patients (85.6%) are referred from various secondary and tertiary centers across western India, with 83.5% already having received first and second-line antibiotics prior to admission with us. Due to well-developed specialty teams, 62.6% of our patients had preexisting comorbidities with multiple healthcare visits and hospitalizations prior to PICU admission. About 84% of patients had at least one invasive device, with more than three-fourths of the study profile being on invasive ventilation. About 21% of the patients had an immunodeficiency disease at admission, possibly explaining the increased susceptibility to infection.
Study of the microbiologic profile showed the following main findings: (1) one-third of community-acquired infections were due to gram-positive organisms, and two-thirds were due to gram-negative organisms. (2) The causative organism in the majority of hospital-acquired infections was gram-negative organisms. (3) Multidrug-resistant organisms (resistant to more than three classes of antibiotics) were isolated in 107 (77%) of the patients in our study, which is a major cause of concern reflecting the rising prevalence of MDRO in the country.
The microbiologic profile in our study is similar to other studies from low- to middle-income countries1,8,11 with a predominance of gram-negative organisms. Out of 107 hospital-acquired respiratory infections in our study, 99% were due to GNB, of which nonfermenting gram-negative bacilli (NFGNB), that is, Acinetobacter, Pseudomonas, and Burkholderia, were the most frequent causative organisms (71/107). Other studies on ventilator-associated pneumonia showed the prevalence of GNB to be 70–100%.12,14
The predominant organism causing bloodstream HAI in our study was gram-negative (77%), followed by Candida species (22%). GNB comprised 31–88% of studies on nosocomial BSI,11,14,17 In a multicenter study from 89 intensive care units (adult and pediatric) from 26 hospitals in India, there were 2,622 reported hospital-acquired BSIs.11 The commonest organisms were gram-negative organisms, that is, Klebsiella (25%), Acinetobacter (21%), and Candida species (12%), similar to our study. Gram-positive organisms were seen in 16%. The study included data from 232 positive cultures from 14 PICUs.
A. baumannii was the commonest cause of hospital-acquired infection in our study. This has been seen in other studies as well. More than half of the GNB organisms in our study comprised nonfermenting gram-negative bacteria, along with emerging organisms such as Elizabethkingia meningoseptica, S. maltophila, and B. cepacia.
More than 80% of isolates of K. pneumoniae and A. baumannii in our study were resistant to cephalosporins, fluoroquinolones, aminoglycosides, as well as carbapenems, which is an alarming trend reported by others as well.7 Studies in children have shown the prevalence of carbapenem-resistant A. baumannii to be 57–87.5%.10,18,21 Carbapenem-resistant K. pneumoniae was seen in 25/29 isolates in our study, while others have reported rates of 4–77%.7,11,19,22
Increasing antibiotic resistance has similarly been reported in neonates23 and children receiving pediatric neurointensive ICU care.24 Carbapenem-resistant Acinetobacter, carbapenem-resistant Klebsiella, and multidrug-resistant Pseudomonas are classified as critical organisms urgently needing research on new antibiotics.25
Elizabethkinga meningosepticum (previously called Flavobacterium meningosepticum / Chryseobacterium meningosepticum), which was seen in 11/110 HAI respiratory isolates and 9/75 blood cultures, is an emerging nosocomial pathogen in PICU,26,27 earlier reported predominantly in neonates and immunocompromised adults. The organism is sensitive to trimethoprim-sulfamethoxazole and minocycline and resistant to carbapenems and colistin.
S. maltophila (previously called Pseudomonas or Xanthomonas maltophila), which was found in 6/75 hospital-acquired BSI, has been reported in immunocompromised children.28 The drug of choice has traditionally been trimethoprim-sulfamethoxazole, while there is increasing evidence that fluoroquinolones and tetracycline derivatives such as minocycline may be reasonable alternatives.29 The organism has inherent resistance to carbapenems and aminoglycosides.
We found 20% of positive blood cultures grown after 48 hours of hospital stay to be due to Candida (15/75). There was a predominance of nonalbicans species as well as a high rate of resistance to fluconazole (13/15). Other studies from PICUs in India have found a prevalence of 8–18%,7,16,30,31 with the majority of isolates being nonalbicans species with increasing fluconazole resistance. There is also an increasing prevalence of multidrug-resistant C. auris and C. krusei.32 While there was a high proportion of resistance to fluconazole (13/15), amphotericin (7/15), and voriconazole (7/16) in our study, the numbers are too small to comment on.
Out of the 139 patients included in our study, 86 (61.9%) survived. Infection with MDRO was associated with increased mortality on multivariate analysis in our study (p = 0.02). Studies in adults have similarly shown an association between MDRO infection and mortality.33,34 This may be due to a delay in appropriate antibiotics or associated factors such as severity of illness. A recent meta-analysis found that AMR was associated with 4.95 million deaths (uncertainty interval 3.62–6.57) worldwide, with higher prevalence in low- and middle-income countries.35
Our study found a progressive increase in antibiotic resistance, especially of Acinetobacter and Klebsiella to carbapenem over time. A retrospective study of A. baumannii bacteremia from a Korean PICU from 2000 to 2016 found that imipenem resistance progressively increased from a period of no resistance (0 of 6 isolates) from the years 2000–2003, half the isolates being resistant (5 of 9) from 2003 to 2008, and all isolates being resistant from 2008 onwards (12 of 12).36
This study has some limitations. It is a retrospective single-center study with a large proportion of children with comorbidities and multiple hospital exposures. Severity of illness and clinical syndromes such as sepsis or septic shock were not described. Testing for resistance genes was not performed.
CONCLUSION
The majority of blood and respiratory infections in critically ill children were due to gram-negative organisms, most of which demonstrated multidrug resistance. There is a trend toward increasing antibiotic resistance over time, especially to carbapenems. Infection with multidrug-resistant organisms is associated with increased mortality in critically ill children.
ACKNOWLEDGMENTS
We gratefully acknowledge Dr Rohan K Bobade, Dr Rushi D Suchak, and Dr Uma S Ali for data from previous audits. We thank Dr Abhiram Khadse for his help with statistics.
ORCID
Isha Bhagat https://orcid.org/0000-0001-8119-5409
Rekha Solomon https://orcid.org/0000-0001-8611-9237
Dhruv Mamtora https://orcid.org/0000-0002-2085-2986
Garima Mehta https://orcid.org/0000-0002-0128-7117
Lakshmi Shobhavat https://orcid.org/0000-0002-7497-7733
REFERENCES
1. Singhal T. Antimicrobial resistance: the ’other’ pandemic!: based on 9th Dr. I. C. Verma Excellence Award for young pediatricians delivered as oration on 19th Sept. 2021. Indian J Pediatr 2022;89(6):600–606. DOI: 10.1007/s12098-021-04008-9
2. Dharmapalan D, Shet A, Yewale V, et al. High reported rates of antimicrobial resistance in Indian neonatal and pediatric blood stream infections. J Pediatric Infect Dis Soc 2017;6(3):e62–e68. DOI: 10.1093/jpids/piw092
3. Saharman YR, Karuniawati A, Severin JA, et al. Infections and antimicrobial resistance in intensive care units in lower-middle income countries: a scoping review. Antimicrob Resist Infect Control 2021;10(1):22. DOI: 10.1186/s13756-020-00871-x
4. Clinical and Laboratory Standards Institute: Performance Standards for antimicrobial susceptibility testing. 30th Ed. CLSI supplement; 2020.
5. CDC/NHSN Surveillance Definitions for Specific Types of Infections. www.cdc.gov nhsn pdfs pscmanual. [Last Accessed on Dec 18, 2023].
6. Magiorakos AP, Srinivasan A, Carey RB, et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect 2012;18(3):268–281. DOI: 10.1111/j.1469-0691.2011.03570.x
7. Wattal C, Raveendran R, Goel N, et al. Ecology of blood stream infection and antibiotic resistance in intensive care unit at a tertiary care hospital in North India. Braz J Infect Dis 2014;18(3):245–251. DOI: 10.1016/j.bjid.2013.07.010
8. Barolia PK, Khera D, Choudhary B, et al. Bacteriological profile of health care associated infection and antibiotic resistance pattern of isolates at PICU in a tertiary care hospital. Indian J Foren Med Toxicol 2021;15(2):483–491. DOI: 10.37506/ijfmt.v15i2.14357
9. El-Nawawy A, Ashraf GA, Antonios MAM, et al. Incidence of multidrug-resistant organism among children admitted to pediatric intensive care unit in a developing country. Microb Drug Resist 2018;24(8):1198–1206. DOI: 10.1089/mdr.2017.0414
10. Divatia JV, Mehta Y, Govil D, et al. Intensive care in India in 2018–2019: the second Indian intensive care case mix and practice patterns study. Indian J Crit Care Med 2021;25(10):1093–1107. DOI: 10.5005/jp-journals-10071-23965
11. Mathur P, Malpiedi P, Walia K, et al. Health-care-associated bloodstream and urinary tract infections in a network of hospitals in India: a multicentre, hospital-based, prospective surveillance study. Lancet Glob Health 2022;10(9):e1317–e1325. DOI: 10.1016/S2214-109X(22)00274-1
12. Vijay G, Mandal A, Sankar J, et al. Ventilator associated pneumonia in pediatric intensive care unit: incidence, risk factors and etiological agents. Indian J Pediatr 2018;85(10):861–866. DOI: 10.1007/s12098-018-2662-8
13. Bhattacharya P, Kumar A, Kumar Ghosh S, et al. Ventilator-associated pneumonia in paediatric intensive care unit patients: microbiological profile, risk factors, and outcome. Cureus 2023;15(4):e38189. DOI: 10.7759/cureus.38189
14. Aygun F, Aygun FD, Varol F, et al. Infections with carbapenem-resistant gram-negative bacteria are a serious problem among critically ill children: a single-centre retrospective study. Pathogens 2019;8(2):69. DOI: 10.3390/pathogens8020069
15. Sachdev A, Gupta DK, Soni A, et al. Central venous catheter colonization and related bacteremia in pediatric intensive care unit. Indian Pediatr 2002;39(8):752–760. PMID: 12196688.
16. Lakshmi KS, Jayashree M, Singhi S, et al. Study of nosocomial primary bloodstream infections in a pediatric intensive care unit. J Trop Pediatr 2007;53(2):87–92. DOI: 10.1093/tropej/fml073
17. Tomar S, Lodha R, Das B, et al. Central-line-associated bloodstream infections (CLABSI): microbiology and antimicrobial resistance pattern of isolates from the Pediatric ICU of a tertiary care Indian hospital. Clin Epidemiol Global Health 2015;3(Suppl 1):S16–S19. DOI: 10.1016/j.cegh.2015.10.008
18. ICMR Antimicrobial Resistance Research and Surveillance. Network Annual Report January to December 2021. [Accessed on Oct 24,2023].
19. Yang Q, Kamat S, Mohamed N, et al. Antimicrobial susceptibility among gram-negative isolates in pediatric patients in Latin America, Africa-Middle East, and Asia from 2016–2020 compared to 2011–2015: results from the ATLAS surveillance study. J Pediatric Infect Dis Soc 2023;12(8):459–470. DOI: 10.1093/jpids/piad055
20. Briassoulis P, Briassoulis G, Christakou E, et al. Active surveillance of healthcare-associated infections in pediatric intensive care units: multicenter ECDC HAI-net ICU protocol (v2.2) implementation, antimicrobial resistance and challenges. Pediatr Infect Dis J 2021;40(3):231–237. DOI: 10.1097/INF.0000000000002960
21. De Oliveira PMN, Buonora SN, Souza CLP, et al. Surveillance of multidrug-resistant bacteria in pediatric and neonatal intensive care units in Rio de Janeiro State, Brazil. Rev Soc Bras Med Trop 2019;52:e20190205. DOI: 10.1590/0037-8682-0205-2019
22. Ayobami O, Brinkwirth S, Eckmanns T, et al. Antibiotic resistance in hospital-acquired ESKAPE-E infections in low- and lower-middle-income countries: a systematic review and meta-analysis. Emerg Microbes Infect 2022;11(1):443–451. DOI: 10.1080/22221751.2022.2030196
23. Russell NJ, Stöhr W, Plakkal N, et al. Patterns of antibiotic use, pathogens, and prediction of mortality in hospitalized neonates and young infants with sepsis: a global neonatal sepsis observational cohort study (NeoOBS). PLoS Med 2023;20(6):e1004179. DOI: 10.1371/journal.pmed.1004179
24. Patel S, Prabhakar H, Kapoor I. Rate of multidrug-resistance to antimicrobial drugs in patients in pediatric neurointensive care. Indian J Crit Care Med 2023;27(1):67–72. DOI: 10.5005/jp-journals-10071-24377
25. World Health Organization. WHO publishes list of bacteria for which new antibiotics are urgently needed. Geneva, 2017. [Update 27 February 2017, cited 11 April, 2019].
26. Erinmez M, Büyüktas Manay A, Zer Y. Investigation of an outbreak of Elizabethkingia meningoseptica on a pediatric intensive care unit. GMS Hyg Infect Control 2021;16:Doc19. DOI: 10.3205/dgkh000390
27. Sahu MK, Balasubramaniam U, C B, et al. Elizabethkingia Meningoseptica: an emerging nosocomial pathogen causing septicemia in critically ill patients. Indian J Crit Care Med 2019;23(2):104–105. DOI: 10.5005/jp-journals-10071-23127
28. Zöllner SK, Kampmeier S, Froböse NJ, et al. Stenotrophomonas maltophilia infections in pediatric patients—experience at a European Center for Pediatric Hematology and Oncology. Front Oncol 2021;11:752037. DOI: 10.3389/fonc.2021.752037
29. Maraolo AE, Licciardi F, Gentile I, et al. Stenotrophomonas maltophilia infections: a systematic review and meta-analysis of comparative efficacy of available treatments, with critical assessment of novel therapeutic options. Antibiotics (Basel) 2023;12(5):910. DOI: 10.3390/antibiotics12050910
30. Singhi S, Ray P, Mathew JL, et al. Nosocomial bloodstream infection in a pediatric intensive care unit. Indian J Pediatr 2008;75(1):25–30. DOI: 10.1007/s12098-008-0002-0
31. Khairat SM, Sayed AM, Nabih M, et al. Prevalence of Candida blood stream infections among children in tertiary care hospital: detection of species and antifungal susceptibility. Infect Drug Resist 2019;12:2409–2416. DOI: 10.2147/IDR.S196972
32. Chakrabarti A, Sood P, Rudramurthy SM, et al. Characteristics, outcome and risk factors for mortality of paediatric patients with ICU-acquired candidemia in India: a multicentre prospective study. Mycoses 2020;63:1149–1163. DOI: 10.1111/myc.13145
33. Falcone M, Tiseo G, Carbonara S, et al. Mortality attributable to bloodstream infections caused by different carbapenem-resistant gram-negative bacilli: results from a nationwide study in Italy (ALARICO Network). Clin Infect Dis 2023;76(12):2059–2069. DOI: 10.1093/cid/ciad100
34. Krapp F, García C, Hinostroza N, et al. Prevalence of antimicrobial resistance in gram-negative bacteria bloodstream infections in Peru and associated outcomes: VIRAPERU study. Am J Trop Med Hyg 2023;109(5):1095–1106. DOI: 10.4269/ajtmh.22-0556
35. Antimicrobial Resistance Collaborators. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Lancet 2022;399(10325):629–655. DOI: 10.1016/S0140-6736(21)02724-0
36. Kim D, Lee H, Choi JS, et al. The changes in epidemiology of imipenem-resistant Acinetobacter baumannii bacteremia in a pediatric intensive care unit for 17 years. J Korean Med Sci 2022;37(24):e196. DOI: 10.3346/jkms.2022.37.e196
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