Antimicrobial Resistance and Microbiological Spectrum among Neonate Acquiring Healthcare-Associated Infections in South India

 

Usha Rani¹, Kiran Chawla², Leslie E Lewis³, Indira Bairy⁴, Shiva Kumar⁵, Pradeep M Muragundi⁶

¹Assistant Professor, Dept. of Health Innovation, Prasanna School of Public Health (PSPH),

Manipal Academy of Higher Education (MAHE), Manipal, Udupi, Karnataka – 576104, India.

²Professor, Department of Microbiology, Kasturba Medical College (KMC),

Manipal Academy of Higher Education (MAHE), Manipal, Udupi, Karnataka – 576104, India.

³Professor and Head, Department of Pediatrics, Kasturba Medical College (KMC),

Manipal Academy of Higher Education (MAHE), Manipal, Udupi, Karnataka – 576104, India.

⁴Professor, Department of Microbiology, MMMC, Manipal Academy of Higher Education (MAHE),

Manipal, Udupi, Karnataka – 576104, India.

⁵Scholar, Department of Pharmaceutical Sciences, Manipal College of Pharmaceutical Sciences,

Manipal Academy of Higher Education, Manipal, Udupi, Karnataka - 576104, India.

⁶Associate Professor, Department of Pharmacy Management, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Udupi, Karnataka - 576104, India.

 

ABSTRACT:

Background: Each year, nearly 0.748 million new-born deaths occur in India, contributing to 1/3^rd of the world’s neonatal death. Healthcare-associated infections (HAIs) are becoming a challenge to all healthcare providers across the globe. The spectrum of microorganism prevalent and its resistance pattern is alarming for the neonates with exceptionally low immunity. The current study is carried out to explore the microbiological pattern and antimicrobial spectrum causing HAIs among neonate. Methodology: A cross-sectional study among 2736 neonate acquiring HAIs (Using CDC and WHO criteria) was carried out to investigate the spectrum of the bacteriological pathogen at level III Neonatal Intensive Care Unit (NICU) associated with tertiary care teaching hospital of coastal Karnataka. Identified strains of microorganism were further classified as Multidrug-resistant (MDR), Extensive drug-resistant (XDR) and Pandrug resistant (PDR) organism based on an international expert proposal for interim definitions for acquired resistance. One millilitre of the blood sample from neonates acquiring HAIs was cultured in BacT, and then bacterial growth was exposed to MALDI-TOF for identification of the pathogen, and antibiotic sensitivity was checked with VITEK®MS system. Reporting of antibiotic susceptibility was done as per Clinical and Laboratory Standards Institute (CLSI) guidelines. Results: Out of total 2736 neonates admitted to NICU during the study period, 1233 neonates were admitted for >48 hours, of which 118 neonates acquired healthcare-associated infections with the rate of HAIs as 9.6 per 100 admissions for >48 hours. A total of 474 blood/ fluid samples from 118 neonates acquiring HAIs were sent to the microbiology lab for further culture and susceptibility testing. Growth of microorganism was obtained for 162 neonatal blood/ fluid samples. The prevalent microorganisms identified were Klebsiella pneumoniae (35%), coagulase-negative Staphylococcus aureus (CONS) (32%), Acinetobacter baumanii (12%), Enterobacter cloacae (8%) and E. coli (8%) and others (5%). The resistance pattern of these microorganisms showed multidrug resistance (MDR), extensive drug resistance (XDR) and pan drug resistance (PDR). Conclusion: Gram-negative microorganisms are posing threat to neonatal population in Southern India. Neonatal survival is challanged by Klebsiella pneumoniae, Enterobacter cloacae and Acinetobacter baumanii leading to nearly 30% mortality is a concern for draining out existing antimicrobial therapy. Increasing prevalence of MDR, XDR and PDR require a tragetted approach to exhibit resistance.

 

 

 

INTRODUCTION:

Antimicrobial resistance has become a threat to all the human being¹. The vulnerable population like neonates when exposed and infected to a microorganism that is showing antimicrobial resistance, chance of survival becomes difficult. Microorganism causing Healthcare Associated Infections (HAIs) can be gram positive, gram negative, or fungi are becoming difficult to treat for their antimicrobial resistance going up to pan drug resistance². Emergence of multidrug resistance in a most vulnerable, immuno-compromised population like neonate is a concern to public health emergency^3–5. There is lack of documentation in the spectrum of microorganism showing multi-drug resistance or pan-drug resistance in neonatal healthcare associated infections^6–8. The study is been carried out to investigate the antimicrobial resistance, microbiological spectrum and antibiotic prescription pattern among neonate with HAIs at a level III NICU located in coastal Karnataka, India. The study will be of help to prepare antibiotic stewardship program for neonatal intensive care unit.

 

METHODOLOGY:

A 28 bedded referral NICU was selected for the study where admission of both extramural and intramural born neonates are hospitalized. The case detection and confirmation was carried out for a newborn admission to NICU >48 hrs using a combination of CDC and WHO recommended clinical findings and diagnostic findings, where presence of at least any two variable of each category confirms the case label as HAIs. Data from November 2016 to June 2018 was collected for neonate acquiring HAIs. The neonates are defined as from the day of birth ‘0’ days to ‘28’days of life; however, each day of life is counted from 24 hours of birth, not at midnight hour. At the study setting the nurse to neonate, the ratio is 1:4 for the non-ventilated patient and 1:3 for the ventilated neonate. There are six resident pediatric trainee doctors and five consultants providing medical care to these neonates. The NICU had both extramural and intramural born neonates for hospitalization. Neonates carrying any other infection from another unit of the hospital or different hospital or infected by mother were excluded from the study. Only infections originating/acquired at the study site after 48 hours of admission were identified and included in the study as per the clinician ascertainment and the diagnostic criteria determining HAIs.

 

One millilitre of blood sample is collected by assigned shift nurse with all aseptic measures in vacutainer and transported with men assistance to microbiology lab within 2 hours of sample collection. The microbiology laboratory is located at a 100-meter distance from the study setting, equipped to carry out conventional microbiological tests. The blood sample was cultured in BacT alert, the respiratory sputum/ wound swab/cerebrospinal fluid (CSF) was cultured on MacConkey and 5% sheep blood agar and chocolate agar. The solid media were incubated aerobically in 5-10% CO₂ incubator for 24-48 hours.

 

If any microorganism growth was observed, then colonies were identified with MALDI-TOF, and antibiotic sensitivity was done with the VITEK®MS system. Antibiotics for sensitivity were selected as per Clinical and Laboratory Standards Institute (CLSI) guidelines. The colistin sensitivity given by the VITEK MS system was not reported, but if any resistance was seen, then it was confirmed with E-strip before its reporting. Identified strains of microorganism were further classified as Multidrug-resistant (MDR), Extensive drug-resistant (XDR) and Pandrug-resistant (PDR) organism based on an international expert proposal for interim definitions for acquired resistance. Class of antibiotics, type of microorganism, type of sample sent to microbiology lab were analyzed and reported using descriptive statistics like the frequency with range and percentage Prior to the commencement of the study, Institutional Ethics Committee approval was obtained with the number MUEC 014/2016-17 and MUEC/Renewal-03/2017. 

 

RESULTS:  

A total of 1233 neonate were admitted for >48 hours in NICU where 118 neonate acquired healthcare associated infections. 437 samples were sent to laboratory on suspicion of HAIs where blood samples were sent for 52.8% times. 66.8% of samples sent for culture grew no microorganism (Table 1).

 

The average length of stay at NICU is 33.7 days ±24 SD that ranged 4 days to 147 days. The median gestational age was 32.4 (Q1, Q3 = 29, 36). Neonatal gestations age distribution showed extreme preterm (9%); very preterm (33%); preterm (4%) ; moderate to late preterm (38%) and term (16%).  The birth weight is ranging from 530 gm to 3860 gram, and median birth weight of the neonates was 1358 grams (Q1, Q3 = 1006, 1836).

 

Neonate born with C-section delivery was 53%. Neonate born at the facility was 56%, born at another facility was 44%; and no neonate was born at home. Male gender was 59%, and female gender was 41% acquiring HAIs. Most of the neonates were improved and discharged (70%) from NICU, however mortality (27%) and lost to follow up (3%) outcome was also recorded.

 

Table 1: Type of samples sent for microbiological investigations

 

Out of the four hundred seventy-four samples sent for investigations to the laboratory, 40% had microorganism growth in culture. Other samples included wound swabs, endotracheal aspirate, and pus swab. Only one each of the wound swab and endotracheal aspirate showed growth of microorganism while the other samples showed no growth. Klebsiella pneumoniae (29%), Acinetobacter baumanii (11%), Enterobacter cloacae (6%), E. coli (6%), Pseudomonas aeruginosa (4%), were the prime gram-negative isolates from these neonates with resistance to antimicrobials (Figure 1). Among all the microorganisms Coagulase-negative staphylococcus aureus (27%) was the only prime isolated as gram-positive microbe (Figure 2).

 

Figure 1: Antimicrobial resistance of gram-negative microorganisms causing HAIs.

 

■Streptococcus sp.

■Enterococcus sp.

■Methicillin-resistant staphylocossus aureus (MRSA)

■Coagulase negative staphylococcus aureus (CONS)

Figure 2: Antimicrobial resistance of gram-positive microorganisms causing HAIs

 

The spectrum of antibiotic resistance among neonates acquiring HAIs in 19 months showed no change with time. Enterobacter cloacae and Klebsiella pneumoniae showed more of MDR pattern, 45.5% and 66% respectively towards antimicrobials (Table 1); whereas, Acinetobacter baumannii showed more of XDR and PDR. These resistant strains of Acinetobacter baumanii were seen more in May to July 2017 and January to March 2018. Except in February 2017, entire study duration observed MDR, XDR and PDR strains of Klebsiella pneumoniae with a peak in March, September of 2017, and June of 2018 for MDR strains. From June to August 2017, a sustained MDR Enterobacter cloacae was found in culture reports followed by XDR in April and June 2018 and PDR in November 2017. E. coli PDR strains were reported in September 2017 and April 2018.

 

β-lactam, second and third-generation cephalosporins showed resistance to Klebsiella pneumoniae. Acinetobacter baumanii was resistant to β-lactam β-lactamase combination inhibitors, third and fourth generation cephalosporin, Fluro-quinolones and carbapenems. Enterobacter cloacae were resistant to β-lactam β-lactamase combination inhibitors, second-generation cephalosporin and Fluro-quinolones. E. coli was resistant to β-lactams, second-generation cephalosporin, Fluro-quinolones, and aminoglycosides.

 

Penicillin, penicillin combinations, and third-generation cephalosporin class of antibiotics were often prescribed whenever suspected for the presence of infection (Figure 3). Frequently a combination of any two antibiotics from three class of antibiotics, i.e. β-lactams, β-lactam β-lactamase combination inhibitors and aminoglycosides that include amikacin, ampicillin, cefoperazone/ sulbactam and piperacillin-tazobactam were prescribed for a maximum duration of 31 days whenever culture report was positive or clinical HAIs was diagnosed.

 

Figure 3: Antibiotic prescription among neonate acquiring HAIs

 

The median duration of antibiotic prescription for neonate acquiring HAIs was aminkacin:12 days (Q1, Q3 = 2, 31 days); ampicillin: 4 days (Q1, Q3 = 2, 31 days); cefoperazone/sulbactam: 10 days (Q1, Q3 = 2, 27days); ciprofloxacin: 9 days (Q1, Q3 = 2, 24 days); and piperacillin-tazobactam was 7 days (Q1, Q3 = 2, 29 days).

 

 

DISCUSSION:

The current article is the first detailed epidemiological report from India reporting MDR, XDR and PDR strain along prescription pattern of antimicrobials for neonates acquiring HAIs.The study delineates the microbiological spectrum and antimicrobial resistance patterns associated with neonate acquiring HAIs at a NICU associated with a tertiary care teaching hospital. The study will be of help to prepare antibiotic stewardship program for neonatal intensive care unit.

 

Geographical location and the type of hospital can be a contributor to the diverse incidence density of cases with HAIs^9,10. A study from Italy reports the rate of HAIs as 9 per 100 neonates with an incidence density of 3.5 per 1000 days of hospital stay¹¹, and we report 9.6 per 100 neonates as the rate of HAIs with incidence density of 5.37 per 1000 days of hospital stay. There are few studies from western and northern India reporting 5.7% to 31% bacteremia^12–14, we observed 10.4% bacteremia at current study setting. The standardisation in reporting of the cases with HAIs that should include the prevalence, incidence density and the bacteremia rate was not found in the published literature.

 

The spectrum of microorganisms causing HAIs may vary as per geographical locations. It has been reported from western and developed countries that gram-positive microorganism are more prevalent than gram-negative microorganisms^1,15. The present study noticed the predominance of gram-negative microorganism (61%) over gram-positive microorganisms (39%). One of the Indian studies has reported gram-positive microorganisms (21.4%) with MRSA dominanacy¹⁶ whereas in our study gram-positive microorganisms (37%) with coagulase-negative staphylococcus aureus (CONS) (30%) dominancy was observed. Another study from north-east India by Rajlakshmi et al. has reported 73.7% gram-negative organisms⁵.

 

A study from Nepal in the year 2013 by N. Gayawali et al. reported 44.1% gram-positive microorganisms with preponderence of Staphylococcus aureus without segregation into outpatient and inpatient admission. They reported 13.5% Klebsiella pneumoniae cases¹⁷, whereas, in the current setting, 29.6% of the cases were infected with Klebsiella pneumoniae. There can be variations in microbes within India too due to the difference in environmental conditions and practices^18–20. There are multiple reporting of outbreaks from time to time whereas reporting of an epidemiological study is very limited.

 

There are epidemiological reports from northern and western India among neonatal population reporting isolates of Klebsiella pneumoniae, Acinetobacter sp. and Staphylococcus aureus bacteremia in both early and late-onset sepsis^12,17,21,22. The typical microorganisms reported is Serratia marcescens, Staphylococcus aureus, Trichosporon asahii, E.coli and Candida sp.^3,23–25. A study from western India by Muley et al. has reported in Acinetobacter sp. (10.8% of all cases of septicemia) where reporting of Acb complex strains showing multi-drug resistance was made and found Amikacin, imipenem and meropenem as the most effective drug of choice⁴. Most of the studies report and analyse early and late-onset sepsis without taking stock of HAIs or report sub group analysis of the same^6,7,9,26. Such published literature limit the comparison of the study findings.

 

Earlier Kamath et al. have reported 71.8% gram-negative bacilli with a predominance of Acinetobacter baumanii, Klebsiella pneumoniae, E. coli, Enterobacter cloacae along with MRSA and other gram-positive microorganisms among the neonatal population²⁷. The study done in 2008 showed 16.4% Klebsiella pneumoniae, whereas we found an increase in the prevalence of  Klebsiella pneumoniae (29%) after a decade.

 

Susceptibility pattern of our predominant microorganism Klebsiella pneumoniae isolates showed 74% sensitivity to aminoglycosides, 67% to sulfonamides, 69% to fluoroquinolones, up to 90% to carbapenems, 19%, 51% and 37% to second, third and fourth generation cephalosporins respectively, up to 50% to β-lactam β-lactamase combination inhibitors but complete resistance to β-lactams, which is in contrast to Manoj Kumar et al. reporting 100% resistance to cefotaxime and ceftazidime²⁸. Our findings are in similar lines with findings of Gayawali et al. and Jyothi et al. showing nearly >50% resistance to almost all the types of antibiotics^17,21.

 

Acinetobacter baumanii, showed max 57% susceptibility to third-generation cephalosporins, 22% to fluoroquinolones, 14% to carbapenems, 16% to sulfonamides and only 7% to β-lactam β-lactamase combination inhibitors. The other class of antimicrobials were not tested for its susceptibility. Contrastingly Jeyamurugan et al. showed 100% sensitivity to β-lactam β-lactamase combination inhibitors, and we found its limited use for Acinetobacter baumannii²⁹.

 

In this setting amikacin, amoxicillin and piperacillin-tazobactam which are used by our clinicians were the choice of antimicrobials for HAIs, where Klebsiella pneumoniae and Acinetobacter baumanii were the predominantly isolated microorganisms similar to other studies^8,30,31. The usage of antibiotics showed a deviated pattern from susceptibility that is brought in to the light of HICC and clinicians to choose the right antibiotics for the reduction of AMR.

Prevalence of MDR, XDR and PDR may vary from study setting based on various environmental factors. A study from north-east reported predominance of Acinetobacter sp. showing MDR (50%) but the isolation of microorganisms causing HAIs was not sought. This study reported on Acinetobacter pan-drug resistance and more than four antibiotics resistance⁵.

 

There are limited studies globally where microbial flora causing HAIs has been extracted and also the comment on the prevalence of MDR, XDR and PDR organism is sought^12,17,21,22. There is a definite dearth of studies from India reporting MDR, XDR and PDR strain among microbiological isolates causing neonatal HAIs. In the current study reporting of MDR, XDR and PDR are done in isolation for the microorganisms causing HAIs. Such reporting will help to develop antimicrobial policy and will help to reduce further antimicrobial resistance.

 

In our study, consideration of PDR microorganisms may be overestimated as the microorganism might be colistin sensitive if checked as per the guidelines. The colistin drug was not tested because our lab setting reports the susceptibility by using the VITEK® system, which does not recommend reporting the colistin resistance using their system.

 

The maternal history of antenatal use of antibiotics might be a determinant for the development of such resistance to antibiotics, but the maternal history of these neonates did not reveal such exposure. A 28% mortality among patient with HAIs is high, and this high mortality could be due to increased prevalence of antimicrobial resistance or incorrect choice of antibiotics that were found in this study, though there could be other factors also. At any given time, the neonate was exposed to two categories of antibiotics on suspicion of originating infection and these antibiotics were stopped within 72 to 96 hours if the culture report comes out to be negative. However, exploring the setting specific microbiological profile and its susceptibility will help to reduce the antimicrobial resistance and will improve the patient outcome both in terms of cost and life^30–32. Prescription of few class/types antimicrobial therapy will help to restrict the burden of resistance microorganism in NICU.

 

CONCLUSION:

Gram-negative microorganisms are posing threat to neonatal population at hospital of Southern India. Challange is faced among neonates infected with Klebsiella pneumoniae, Enterobacter cloacae and Acinetobacter baumanii leading to nearly 30% mortality is a concern for draining out existing antimicrobial therapy. Increasing prevalence of MDR, XDR and PDR require a tragetted approach to exhibit resistance.

CONFLICT OF INTEREST:

The authors have no conflicts of interest regarding this investigation.

 

ACKNOWLEDGEMENTS:

Authors would like to acknowledge and thank Dr. Asha Kamath, Associate director and Head department of data sciences, Prasanna school of Public Health, MAHE, Manipal for proof-reading the manuscript and providing critical suggestions. We also thank Manipal Academy of Higher Education for providing space and necessary permissions to carry out research.

 

REFERENCES:

1.   WHO. Antimicrobial resistance. Available at: https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance. Accessed June 17, 2019.

2.    Magiorakos A-P., 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 Background Emergence of resistance to multiple antimicrobial agents in pathogenic bac. Clin Microbiol Infect 2012;18:268–81. Doi: 10.1111/j.1469-0691.2011.03570.x.

3.    Sharma P., Kaur P., Aggarwal A. Staphylococcus aureus- the predominant pathogen in the neonatal ICU of a tertiary care hospital in Amritsar, India. Journal of Clinical and Diagnostic Research 2013;7(1):66–9. Doi: 10.7860/JCDR/2012/4913.2672.

4.    Muley V., Bhore A., Shete V., Ghadage D. Acinetobacter septicemia in neonates admitted to intensive care units. Journal of Laboratory Physicians 2010;1(2):73. Doi: 10.4103/0974-2727.59704.

5.    Viswanathan R., Singh AK., Basu S., Chatterjee S., Roy S., Isaacs D. Multi-drug-resistant, non-fermenting, gram-negative bacilli in neonatal sepsis in Kolkata, India: a 4-year study. Paediatrics and International Child Health 2013; 34(1):56–9. Doi: 10.1179/2046905513y.0000000072.

6.    Abbas HA., Kadry AA., Shaker GH., Goda RM. Resistance of Escherichia coli and Klebsiella pneumoniae isolated from different Sources to β-lactam Antibiotics . Research Journal of Pharmacy and Technology 2017; 10(2):589. Doi: 10.5958/0974-360X.2017.00116.0.

7.    Anima N., Dhamodharan S., Nayak BK. Antibiotic resistance pattern exhibited by Esbl (Extended spectrum β-lactamases) in multidrug resistant strains, Escherichia coli. Research Journal of Pharmacy and Technology 2017; 10(11):3705–8. Doi: 10.5958/0974-360X.2017.00672.2.

8.    Aljanaby AAJ., Aljanaby IAJ. Profile of antimicrobial resistance of aerobic pathogenic bacteria isolated from different clinical infections in Al-Kufa Central Hospital -Iraq during period from 2015 to 2017. Research Journal of Pharmacy and Technology 2017; 10(10):3264–70. Doi: 10.5958/0974-360X.2017.00579.0.

9.    Shidiki A., Pandit B., Vyas A. Incidence and Antibiotic profile of Bacterial Isolates from Neonatal Septicemia in National Medical College and Teaching Hospital, Birgunj, Nepal. Research J Pharm and Tech 2018; 11(6). Doi: 10.5958/0974-360X.2018.00414.6.

10.  Bharadwaj S., Teotia UVS., Singh K., Sharma R., Singh Y. Effect of Antibiotic on Various Microorganisms Isolated from Nosocomial Infected Patients in General Hospital. Research J Pharm and Tech 2014; 7(4).

11.  Crivaro V., Bogdanović L., Bagattini M., et al. Surveillance of healthcare-associated infections in a neonatal intensive care unit in Italy during 2006–2010. BMC Infectious Diseases 2015; 15(1):152. Doi: 10.1186/s12879-015-0909-9.

12.  Muley VA., Ghadage DP., Bhore A V. Bacteriological Profile of Neonatal Septicemia in a Tertiary Care Hospital from Western India. Journal of Global Infectious Diseases 2015; 7(6):75–7. Doi: 10.4103/0974-777X.154444.

13.  Pawar A., Raut A., Kalrao V., Jacob J., Godha I., Thomas R. Etiology and Clinical Outcomes of Neonatal and Pediatric Sepsis. Archives of Pediatric Infectious Diseases 2016; 4(2). Doi: 10.5812/pedinfect.33602.

14.  Pathak A., Singh P., Jain S., Dhaneria M., Lundborg CS. Incidence and determinants of health care associated blood stream infections at a neonatal intensive care unit in Ujjain, India: Results of a prospective cohort study. International Journal of Infectious Diseases 2014; 21:48. Doi: 10.1016/j.ijid.2014.03.518.

15.  Auriti C., Ronchetti MP., Pezzotti P., et al. Determinants of Nosocomial Infection in 6 Neonatal Intensive Care Units: An Italian Multicenter Prospective Cohort Study. Infection Control and Hospital Epidemiology 2010; 31(09):926–33. Doi: 10.1086/655461.

16.  Kamath S., Mallaya S., Shenoy S., et al. Nosocomial infections in neonatal intensive care units: Profile, risk factor assessment and antibiogram. Indian Journal of Pediatrics 2010; 77(1):37–9. Doi: 10.1007/s12098-010-0005-5.

17.  Gyawali N., Sanjana RK. Bacteriological profile and antibiogram of neonatal septicemia. Indian Journal of Pediatrics 2013; 80(5):371–4. Doi: 10.1007/s12098-012-0911-9.

18.  Mehta Y., Jaggi N., Rosenthal VD., et al. Device-Associated Infection Rates in 20 Cities of India, Data Summary for 2004-2013: Findings of the International Nosocomial Infection Control Consortium. Infection Control and Hospital Epidemiology 2016. Doi: 10.1017/ice.2015.276.

19.  Goel K., Randhawa VS., Saili A., et al. Incidence, etiology and risk factors associated with neonatal healthcare- associated conjunctivitis: A Prospective Study from a Tertiary Care Hospital in India. Journal of Tropical Pediatrics 2016; 62(1):10–8. Doi: 10.1093/tropej/fmv064.

20.  Chatterjee S., Datta S., Roy S., et al. Carbapenem resistance in Acinetobacter baumannii and other acinetobacter spp. causing neonatal sepsis: Focus on NDM-1 and its linkage to ISAba125. Frontiers in Microbiology 2016; 7(AUG):1–13. Doi: 10.3389/fmicb.2016.01126.

21.  Jyothi P., Basavaraj MC., Basavaraj P V. Bacteriological profile of neonatal septicemia and antibiotic susceptibility pattern of the isolates. Journal of Natural Science, Biology and Medicine 2013. Doi: 10.4103/0976-9668.116981.

22.  Verma P., Berwal P., Nagaraj N., Swami S., Jivaji P., Narayan S. Neonatal sepsis: epidemiology, clinical spectrum, recent antimicrobial agents and their antibiotic susceptibility pattern. International Journal of Contemporary Pediatrics 2015. Doi: 10.18203/2349-3291.ijcp20150523.

23.  Shakil S., Akram M., Ali SM., Khan AU. Acquisition of extended-spectrum β-lactamase producing Escherichia coli strains in male and female infants admitted to a neonatal intensive care unit: Molecular epidemiology and analysis of risk factors. Journal of Medical Microbiology 2010; 59(8):948–54. Doi: 10.1099/jmm.0.020214-0.

24.  Basu S., Kumar R., Tilak R., Kumar A. Candida blood stream infection in neonates: Experience from a tertiary care teaching hospital of Central India. Indian Pediatrics 2017; 54(7):556–9. Doi: 10.1007/s13312-017-1067-5.

25.  Vashishtha VM., Mittal A., Garg A. A fatal outbreak of Trichosporon asahii sepsis in a neonatal intensive care Unit. Indian Pediatrics 2012; 49(9):745–7.

26.  Chaturvedi R., Chandra P., Mittal V. Biofilm Formation by Acinetobacter Spp. in association with Antibiotic Resistance in clinical samples Obtained from Tertiary Care Hospital. Research Journal of Pharmacy and Technology 2019; 12(8):3737–42. Doi: 10.5958/0974-360X.2019.00620.6.

27.  Kamath S., Mallaya S., Shenoy S., et al. Nosocomial infections in neonatal intensive care units: profile, risk factor assessment and antibiogram. Indian Journal of Pediatrics 2010; 77(1):37–9. Doi: 10.1007/s12098-010-0005-5.

28.  Kumar M., Dutta R., Saxena S., Singhal S. Risk factor analysis in clinical isolates of ESBL and MBL (Including NDM-1) producing escherichia coli and klebsiella species in a tertiary care hospital. Journal of Clinical and Diagnostic Research 2015; 9(11):DC08-DC13. Doi: 10.7860/JCDR/2015/15672.6766.

29.  Jeyamurugan T., Ragulganesh R., Sucilathangam G., Ashihabegum MA., Velvizhi G., Palaniappan N. Acinetobacter spp.: An emerging pathogen in neonatal septicaemia. Journal of Clinical and Diagnostic Research 2012; 6(5):805–6.

30.  Pranay W., Ankita W., Rishabh S., Prateek R., Awani R. Antibiotic Therapy in Pediatric Patients. Research J Pharm and Tech n.d.; 3(1). Doi: 10.1086/422881.

31.  Joel JJ., Bhat VS., Rose AE. Study on Drug Utilization Pattern of Antibiotics in Respiratory Tract Infections. Research J Pharm and Tech 2019; 12(3). Doi: 10.5958/0974-360X.2019.00197.5.

32.  Thomson WM., Sudha M., Venkateswaramurthy N., Sambath Kumar R. A Review on the Irrational Antibiotics usage in Pediatrics for Respiratory Tract Infections. Research J Pharm and Tech 2019; 12(10). Doi: 10.5958/0974-360X.2019.00888.6.

 

 

 

Accepted on 10.01.2022           © RJPT All right reserved

Research J. Pharm. and Tech 2022; 15(12):5645-5650.