|Year : 2018 | Volume
| Issue : 3 | Page : 141-145
A retrospective cohort study patient chart review of neonatal sepsis investigating responsible microorganisms and their antimicrobial susceptibility
Mountasser M Al-Mouqdad1, Faisal A Alaklobi2, Fahad H Aljobair2, Tariq M Alnizari3, Muhammed Yassen Taha4, Suzan S Asfour5
1 Hospital of Pediatrics, Neonatal Intensive Care Unit, Riyadh, Saudi Arabia
2 Hospital of Pediatrics, Department of Pediatric Infectious Diseases, Riyadh, Saudi Arabia
3 Department of Regional Laboratory, King Saud Medical City, Riyadh, Saudi Arabia
4 Department of Pharmacy, King Saud Medical City, Riyadh, Saudi Arabia
5 Department of Clinical Pharmacy, King Saud Medical City, Riyadh, Saudi Arabia
|Date of Web Publication||2-Aug-2018|
Dr. Mountasser M Al-Mouqdad
Hospital of Pediatrics, Neonatal Intensive Care Unit, King Saud Medical City, Riyadh
Source of Support: None, Conflict of Interest: None
Background and Aims: Microorganisms responsible for neonatal sepsis have developed increased drug resistance to commonly used antibiotics making treatment extremely difficult. To select an appropriate antibacterial therapy, the common pathogens causing sepsis in neonates and their bacterial resistance should be known first. The present study was designed to investigate the microorganisms responsible for neonatal sepsis in King Saud Medical City Neonatal Intensive Care Unit (NICU). In addition, we sought to determine the antibiotic susceptibility of the isolated microorganisms for planning a strategy for the management of neonatal sepsis. Subjects and Methods: This study is a retrospective cohort study, was conducted at the NICU of King Saud Medical City. A total of 295 inborn premature infants aged ≤180 days and received antibiotics. The study lasted for 12 months. The primary outcome measures were the incidence of the bacterial infection and its etiology in cases with suspected sepsis. The secondary outcome measure was the bacterial sensitivity to antibiotics used. Results: A total of 70 different microorganisms were isolated from culture-positive samples from 57 neonates. Gram-positive organisms (57%) were more common than Gram-negatives (38.5%), coagulase-negative staphylococci were the most isolated pathogens (44%), and the prevalence of fungal sepsis was low (4.3%). The prevalence of antimicrobial resistance was low. Among Gram-positives, there were only three methicillin-resistant Staphylococcus aureus isolates, and no vancomycin-resistant enterococci. Whereas three of the Gram-negative isolates were resistant, two Enterobacter cloacae and one Pseudomonas aeruginosa, and none of Candida species were resistant. Conclusion: Antimicrobial resistance was low in our study, mostly because of the restriction of broad-spectrum antibiotics.
Keywords: Antimicrobial susceptibility, bacterial resistance, neonatal sepsis
|How to cite this article:|
Al-Mouqdad MM, Alaklobi FA, Aljobair FH, Alnizari TM, Taha MY, Asfour SS. A retrospective cohort study patient chart review of neonatal sepsis investigating responsible microorganisms and their antimicrobial susceptibility. J Clin Neonatol 2018;7:141-5
|How to cite this URL:|
Al-Mouqdad MM, Alaklobi FA, Aljobair FH, Alnizari TM, Taha MY, Asfour SS. A retrospective cohort study patient chart review of neonatal sepsis investigating responsible microorganisms and their antimicrobial susceptibility. J Clin Neonatol [serial online] 2018 [cited 2019 Dec 15];7:141-5. Available from: http://www.jcnonweb.com/text.asp?2018/7/3/141/238398
Neonatal sepsis is one of the primary causes of morbidity and mortality among preterm infants. Microorganisms responsible for neonatal sepsis have developed increased resistance to commonly used antibiotics. Since antibacterial resistance patterns of pathogens vary from one geographical location to another; the common pathogens causing sepsis in neonates as well as their bacterial resistance should be known first to select an appropriate antibacterial therapy. In the present study, we aimed to investigate the microorganisms responsible for neonatal sepsis in King Saud Medical City Neonatal Intensive Care Unit (NICU). In addition, we sought to determine the antibiotic susceptibility of the isolated microorganisms for planning a management strategy.
[TAG:2]Subjects and Methods[/TAG:2]
This is a retrospective cohort study, a patient chart review of neonates admitted to King Saud Medical City's NICU, between July 2015 and June 2016. This study followed the principles of the Declaration of Helsinki, by the Good Pharmacoepidemiology Practices guidelines, and was approved by the Medical Ethical Review Committee of our institution.
The study population included 323 neonates ≤32 weeks, weighing 1.5 kg or less with suspected neonatal sepsis admitted to our NICU during this period. Inclusion criteria were all inborn premature infants aged ≤180 days who were admitted to our NICU and received antibiotics. Exclusion criteria were outborn neonates or ones with major congenital anomalies. The attending physician cared for the admitted neonates using age-related norms and treatment protocols. Patient charts were reviewed retrospectively on discharge from the NICU capturing data about patients' demographics as well as their clinical and outcome data.
Primary outcome measures were the incidence of the bacterial infection and its etiology in cases with suspected sepsis. The secondary outcome measure was the bacterial resistance to antibiotics used. Patients' data were entered into computerized databases for clinical audits and quality assurance. Neonatal sepsis was classified as early-onset sepsis (EOS) if sepsis manifests within the first 3 days of life, or late-onset sepsis (LOS) if it manifests after 3 days of life.
Multiple-drug resistance (MDR) was defined as acquired no susceptibility to at least one agent in three or more antibacterial categories whereas extensive-drug resistance was defined as no susceptibility to at least one agent in all but two or fewer antibacterial categories.
Data were deidentified and entered into SPSS software (Statistical Package for the Social Sciences, version 20.0, SSPS Inc., IBM Corp, Armonk, NY, USA) for statistical analysis, P < 0.05 was considered statistically significant. Patients whose data could not be retrieved were excluded from the study. Data were summarized by mean, standard deviation or median and interquartile range in numerical data, and using frequency (count) and relative frequency (percentage) for categorical data. For comparing categorical data, Chi-square test or Phi and Cramer V test was performed. The exact test was used instead when the expected frequency is <5. Comparisons between quantitative variables were made using Student's t-test and the nonparametric Mann—Whitney test when needed. P < 0.05 was considered statistically significant.
This study included 323 neonates with suspected neonatal sepsis, 28 neonates were excluded from the study; 16 were outborn, six did not take antibiotics, five had major congenital anomalies, and one had major congenital anomalies and was outborn, leaving 295 cases included in the analysis of this study. Of the total number of patients (n = 295), 175 patients were Saudi (59.3%).
Characteristics of neonates with sepsis
A total of 295 neonates, 153 (51.9%) of which were males, with sepsis had their blood screened for bacterial growth, of which 57 (19.3%) were found to be culture positive whereas the remaining 238 (80.7%) were culture negative. Culture positivity was higher among males (n = 33, 21.6%) than among females (n = 24, 16.9%) (P = 0.310). Of the total cases of neonatal sepsis, 1.69% (n = 5) had EOS while 18.3% (n = 54) had LOS. Two cases had both EOS and LOS. The incidence of culture-positive sepsis was significantly higher in neonates with extreme prematurity (29.3%) compared to neonates without extreme prematurity (14.4%) (P = 0.002).
Forty-five mothers suffered from prolonged premature rupture of membrane, out of which nine mothers gave birth to neonates with culture-positive sepsis (20.0%) (P = 0.900). Culture positivity was higher among neonates delivered by spontaneous vaginal delivery (SVD) (23.5%) than among those delivered by cesarean section (15.7%) [Table 1].
From the 57 culture positive sepsis neonates, 70 different types of microorganisms were isolated. The incidence of infection by Gram-positive microorganisms was 57.2% (n = 40) while that of Gram-negative microorganisms was 38.6% (n = 27). Fungal infections accounted for 4.2% (n = 3) of the culture positive cases. Coagulase-negative staphylococci (CoNS) were the most commonly isolated organisms (n = 31, 44%), and Staphylococcus epidermidis was the most frequent of these (80.7%) Staphylococcus aureus was less common (n = 5, 13.1%), and 60% of these were methicillin-resistant S. aureus (MRSA). The prevalence of MRSA was 1% in all cases with suspected sepsis and 4.3% of all isolates. Group B Streptococcus and Enterococcus were uncommon (one isolate each, 2.7%). Among Gram-negatives, Escherichia More Details coli, Klebsiella species, Enterobacter cloacae and Pseudomonas aeruginosa were the most commonly isolated pathogens (18.5% each), while Serratia marcescens, Acinetobacter species and Kluyvera ascorbata were less common. There were only three fungal isolates (4.3%), all were Candida [Table 2].
|Table 2: Isolated microorganisms and antimicrobial susceptibility (n=70)|
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Antimicrobial susceptibility of the isolates
One hundred percent of CoNS were susceptible to vancomycin and linezolid, while susceptibility to rifampin, trimethoprim/sulfamethoxazole, clindamycin, and gentamycin were 90%, 74%, 42%, and 6%, respectively. On the other hand, 100% of S. aureus isolates were susceptible to vancomycin, linezolid, rifampin and clindamycin, 80% to trimethoprim/sulfamethoxazole, and 60% to gentamicin. Group B Streptococcus, Enterococcus faecalis, and corynebacteria were penicillin sensitive.
Ninety-three percent of all Gram-negative bacilli isolates were susceptible to gentamicin, amikacin, and colistin whereas 90% were susceptible to cefepime and ciprofloxacin, and 85% to ceftazidime. All the Gram-negative isolates except one pseudomonal isolate were susceptible to carbapenems (meropenem and imipenem).
All the Candida isolates were susceptible to fluconazole, amphotericin B, and echinocandins [Table 3].
Infection including sepsis is a major cause of morbidity and mortality in neonates, particularly premature infants.
The signs of neonatal sepsis in premature infants are usually subtle and nonspecific; hence, the common practice in suspected cases is to do septic workup and start empiric antibiotics pending culture results which turn to be negative in the majority of cases.
In this study, culture-proven sepsis was found to be 19.3% of suspected sepsis cases. Males showed higher blood culture positivity (33 of 57 cases, 57.9%) than females (24 of 57 cases, 42.1%), which is comparable with other studies., The significant high incidence of culture-proven sepsis among neonates with extreme prematurity that was observed in the study can be attributed to their undeveloped immune system and the lack of maternally transferred antibodies that normally occur late in pregnancy.
The incidence of EOS (5 of 59 cases, 8.5%) was significantly lower than LOS (54 of 59 cases, 91.5%), which is in agreement with a previous study conducted by Bulkowstein et al.
There was no difference in the percentage of culture positivity in neonates whose mothers had suffered from prolonged premature rupture of membrane and those whose mothers did not. The higher incidence of culture positivity found in neonates delivered by SVD than in those delivered by cesarean section can be due to infection occurring during birth; when the neonate moves through the vagina.
Gram-positive bacteria were found to be more common than Gram-negative bacteria, and CoNS were the predominantly isolated pathogens, particularly in LOS. This is similar to the finding of other studies,,, and can be attributed to the usage of vascular catheters. The Group B Streptococcus was rare (only one isolate) lower than other reports, which possibly because of usage of intrapartum antibiotic prophylaxis.
Among Gram-negative bacteria, E. coli, Klebsiella species, E. cloacae, and P. aeruginosa were the most common pathogens. Three-Gram-negative isolates, Two E. cloacae, and one P. aeruginosa were resistant. The remaining isolates were highly susceptible to aminoglycosides, cephalosporins, and carbapenems.
The low prevalence of multidrug-resistant bacteria in our study is mainly because of restriction of the use of broad-spectrum antibiotics. We use the empiric therapy of ampicillin plus gentamicin for EOS, and cloxacillin plus gentamicin, or amikacin if received gentamicin recently, for LOS. We restrict the use of third-generation cephalosporins to the cases of suspected or confirmed meningitis, vancomycin to suspected MRSA, and carbapenems to cases of MDR gram-negative bacteria.
The prevalence of fungal sepsis in very low birth weight premature infants in our study (1%) is lower than reports in other studies (2%—6.8%)., This can be attributed in addition to the restriction of broad-spectrum antibiotics to the use of antifungal prophylaxis in extremely premature infants.
LOS in neonates was found to be significantly more common than early-onset sepsis. In addition, Gram-positive microorganisms were more frequently encountered, and more specifically S. epidermidis. The antimicrobial resistance was low in our study, mostly because of restriction of broad-spectrum antibiotics.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3]