Open Access Original Article

Clinical Guideline Adaptation for Treatment of Neonatal

Sepsis Based on Frequency of Microbial Agents
Mohammad Bagher Hosseini¹, Shahram Abdoli Oskouei¹, Fariba Heidari², Amin
Sadat Sharif 3, Zakeiye Salimi4, Seyed Amir Abbas Sharif1*
1. Pediatric Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
2. School of Medicine, Department of Community and Family Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
3. School of Medicine, Department of Pediatrics, Tehran University of Medical Sciences, Tehran, Iran
4. Neonatal Intensive Care Unit, Alzahra Teaching Hospital, Tabriz University of Medical Sciences, Tabriz, Iran

ABSTRACT
Background: Sepsis is one of the most important causes of death in infants. The pattern of bacterial agents responsible
for neonatal septicemia changes over time. The main aim of the present study was to provide a clinical guideline
adapted for treatment of neonatal sepsis based on the frequency of microbial agents in the Neonatal Intensive Care
Unit of Alzahra Hospital, Tabriz, Iran.
Methods: The clinical guideline adaptation is conducted based on the ADAPTE Resource Toolkit for Guideline
Adaptation (version 2.0) from December 2016 to January 2018. For data collection, the specialized websites were
identified, then an internet search method was used for gaining clinical guidelines and medical literature databases. A
panel was established with members of multi-specialties and the obtained guidelines were examined and evaluated. In
the end, the final guideline was selected and translated.
Results: Regarding the guideline, employing antibiotics should start when the neonate is < 35 weeks and premature
rupture of membrane (PROM) happened < 18 h. Moreover, it could be employed when the neonate did not receive
antibiotics, the gestational age (GA) is < 35 weeks with a PROM < 18 h or a GA < 37 weeks with a PROM ≥ 18 h.
Conclusion: Implementation of the neonatal sepsis treatment guideline leads to a unified method of treatment,
reduces the risk of antibiotic resistance, and decreases the mortality and morbidity associated with sepsis.

Keywords: Antibiotic treatment, Clinical guideline, Microbial agents, Neonatal sepsis

Introduction
Sepsis is defined as systemic inflammatory is the most common cause of neonatal mortality,
response syndrome, an inflammatory cascade, which is responsible for 30-50% of the neonatal
which is initiated by a host in response to deaths in developing countries (8). Despite recent
infection (1). Neonatal sepsis is a bacterial advances in healthcare and antibiotic therapy, of
infection that initially affects blood flow in infants all children who died under 5 years of age, 51.8%
during the first four weeks of life (2, 3). The died from infections and 44% died in the neonatal
prevalence of sepsis was reported in different period (9, 10). In addition, these infants are at risk
countries, in developed countries it is estimated to for infections and resistant organisms due to long-
be 1-4 per 1,000 live births, while in poor and term hospitalization in the Neonatal Intensive
developing countries, it is reported to be almost Care Unit (NICU) and exposure to various invasive
ten times higher (4, 5). methods and interventions (5, 11).
Although, progress in medical technology has According to the studies performed in this
improved the survival of very low birth weight regard, causes of neonatal sepsis differ in different
(VLBW) infants with birth weight < 1,500 g (6, 7). societies and even in different hospitals. In
These infants are still at high risk of sepsis. Sepsis developed countries, the most common organism

* Corresponding author: Seyed Amir Abbas Sharif, Pediatric Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Tel: +989133198472; Email: [email protected]

Please cite this paper as:

Hosseini MB, Abdoli Oskouei S, Heidari F, Sharif AS, Salimi Z, Sharif SAA. Clinical Guideline Adaptation for Treatment of
Neonatal Sepsis Based on Frequency of Microbial Agents. Iranian Journal of Neonatology. 2020 Mar: 11(1). DOI:
10.22038/ijn.2019.38426.1605
Hosseini MB et al Clinical Guideline Adaptation for Treatment of Neonatal Sepsis Based on the Frequency of Microbial Agents

causing sepsis in the 1930s and 1940s was group different antibiotics develop antibiotic resistance,
A Streptococcus beta-hemolytic. This agent was varying prevalence and causes of septicemia in
replaced by Staphylococcus aureus and Coliform different societies, it is necessary to perform
bacteria in the 1950s and since the late 1950s, continuous epidemiological monitoring in
Escherichia coli and beta-hemolytic streptococcus hospitals, especially in NICU, and employing an
group B have been responsible for around 60-70% antibiotic guideline based on the relevant
of the causative agents of the neonatal sepsis. microbial agents. Currently, in most treatment
Even in developed countries, the causes of sepsis centers, treating neonatal sepsis is carried out
have varied over time and in different regions (5, based on received information from studies
12, 13). conducted in developed countries. However, due
Although different diagnostic methods were to social, cultural, and geographic differences the
employed for neonatal sepsis, managing sepsis in septic bacteria pattern in our region is likely to
neonates involves supportive care and antibiotic differ. On the other hand, the absence of an
therapy, which in turn, includes early empirical agreed-upon clinical guideline by all the
therapy and specific microorganism treatment. neonatology faculty members leads to different
Bang Atlante et al. (1999) found out that home opinions on the prescription of antibiotic
visits by rural health personnel on the first day of medications and other supportive therapies for
birth and prescribing injection antibiotics could patients with sepsis. The current study aimed at
significantly reduce neonatal sepsis morbidity and adapting a clinical guideline for treating neonatal
mortality rates in low-income countries (14). sepsis based on the frequency of microbial agents.
Since antibiotic therapy is considered to be the
main way of neonatal sepsis management, Methods
empirical treatment is the subject of an ongoing Study design and population
discussion. Early intravenous administration of This study was carried out in four main stages
antibiotics in the case of infection is intended to from December 2016 to January 2018. To present
reduce the delay in the treatment of sepsis, which a clinical guideline for the cases of neonatal sepsis
is especially important in the neonates with in the NICU Department of the Al-Zahra Hospital,
symptoms and circulatory instabilities (15). Tabriz, Iran. The materials of this study were the
Experimental antibiotic therapy in early-onset articles and clinical guidelines proposed for
sepsis is often an effective method for treating treating neonatal sepsis available in various
Gram-negative and Gram-positive microorganisms. sources. The process of adapting the clinical
Moreover, it should always be remembered that guideline is shown in Figure 1.
Listeria is a potential cause of early-onset sepsis in
neonates. Compared to the administration of a Methods
single antibiotic at the time, it seems necessary to The clinical guideline adaptation was
administer two antibiotics simultaneously to cover conducted based on ADAPTE Resource Toolkit for
a broader spectrum of resistant bacteria (16). Guideline Adaptation (version 2.0). The target
Clinical guidelines are systematic set of the users for this clinical guideline consisted of
latest and most prestigious scientific evidence, neonatologist, laboratory experts, and specialists.
categorizing clinical approaches for a patient are At the first stage of the adaptation, the clinical
according to their priorities, effectiveness, and guideline for antibiotic treatment of sepsis, all
cost-effectiveness. In developing countries, it is published clinical guidelines, and medical
always argued that the number of credible literature databases on neonatal sepsis treatment
indigenous evidences limited and if the evidences were studied and evaluated. Then, several clinical
are supposed to be taken from developed guidelines were selected, including 14 related
countries, why bother to do what has already been databases, consisting of 7 clinical guideline
conducted? In response to this argument, databases and 7 medical literature databases
guideline adaptation was suggested. Guideline (Table 1).
adaptation is a systematic look at the available In the second step, the obtained guidelines
guidelines to find the most relevant ones for the were critically correlated with the clinical
patient circumstances and integrate it with the questions and the items that were less relevant to
cultural and regional requirements of the target the key question were eliminated. At the third
population, as well as the health facilities (17). stage, after the initial screening of the guidelines,
Due to changing pattern of bacterial agents the quality, validity, content and compatibility,
responsible for neonatal septicemia, usage of and availability of the full version, update and

2 Iranian Journal of Neonatology 2020; 11(1)

Clinical Guideline Adaptation for Treatment of Neonatal Sepsis Based on the Frequency of Microbial Agents Hosseini MB et al

Design a Clinical
Question

Search and find Guidelines

Criticism of the Guidelines

Selection and decision-making

Translation and preliminary drafting

Judgment

Multi-panel session for localization

Final Guideline Report

Performance

Evaluation

Figure 1. Process of the clinical guideline adaptation

Table 1. Searchable Databases

Clinical Guideline Database Medical Literature Database
National Guideline Clearing house PubMed
Guidelines International Network Scopus
National Institute for Health and Clinical Excellence Up to Date
Scottish Intercollegiate Guidelines Network (SIGN) Trip Database
Guidelines Advisory Committee Google Scholar
National Health and Medical Research Council Magiran
WHO | World Health Organization SID

proper organization by Appraisal of Guidelines bacteriologists, and pharmacologists. The next

Research & Evaluation (AGREE) software were step was sharing the resulting information with
examined by the experts. Considering ADAPTE, the panel members. The data was examined and
the most appropriate guideline was selected and evaluated to exclude and eliminate cases that
translated. Based on this guideline, a primary were less relevant to the key questions. Then final
draft of the sepsis treatment guideline was guideline and recommendation were written and
prepared. Then a panel was formed from the the final report was prepared. Before the release
neonatology faculty members, gynecologists, of the final version, a copy of it was given to the
pediatricians of infectious diseases, pathologists, multi-specialist panel members, while identifying

3 Iranian Journal of Neonatology 2020; 11(1)

Hosseini MB et al Clinical Guideline Adaptation for Treatment of Neonatal Sepsis Based on the Frequency of Microbial Agents

the strengths and weaknesses, modifications were sensitivity profile are vital (18-22).
made. Then, among four guidelines, the most According to studies carried out in developing
appropriate one (Management of Neonates with countries, clinical sepsis is estimated to range
Suspected Proven Early-Onset Bacterial Sepsis) from 49 to 170 per 1,000 live births, as well as the
published by the American Academy of Pediatrics number of culture-positive sepsis, is estimated to
was selected. At the fourth step, the final guideline be 16 per 1,000 live births (19-23).
was translated. After finalizing the guideline, it
would be implemented for three months to Definitive sepsis
evaluate the results. In this type of sepsis, the infant experiences at
least one of the following signs or symptoms:
Measuring tools Temperature higher than 37.3°C, hypothermia
For data collection, first, the specialized (temperature<36°C), instability of temperature,
websites were identified and an Internet search changes in consciousness, change of tone,
method was used for finding clinical guidelines decrease in number of neonatal reflexes, seizure,
and medical literature databases. apnea, cyanosis, respiratory distress (tachypnea
with respiratory rate of >60 breaths per minute in
Inclusion criteria and exclusion criteria term infants and more than 70 in preterm infants,
In this study, the inclusion criteria were all grunting, nasal flaring, intercostal and subcostal
the clinical guidelines and medical literature retractions), new or progressive bradycardia,
databases related to neonatal sepsis. Exclusion decreased blood pressure, vomiting, diarrhea,
criteria were all the clinical guidelines and abdominal distension, and jaundice along with the
medical literature databases that were rejected in growth of a specific pathogen from blood, urine,
examination and evaluation by AGREE software or and cerebrospinal fluid (CSF).
by experts for different reasons such as being
unrelated or not being updated. Possible sepsis
This type of sepsis refers to the cases, showing
Ethical considerations at least one of the symptoms and clinical signs
Ethical approval was received from the Ethics listed above. These symptoms are not related to
Committee of Tabriz University of Medical another known cause, blood culture, other fluids,
Sciences, Iran. Additionally, official permission or finding microorganisms and antigens in blood
was obtained from the hospital where the study and the other fluid. The infant will be diagnosed
was conducted. In order to perform the present with this type of sepsis if at least one of the
study, a license was granted from Ethics following two conditions is met:
Committee of Tabriz University of Medical  A test result indicating that the C-reactive
Sciences with the registration number of protein (CRP) level is higher than 10 mg/l (more
IR.TBZMED.REC.1394.1045. Furthermore, collected than 2 times in qualitative testing).
information remained confidential and informed  Or 3 of the following criteria were present:
written consent was obtained from each family,  The total number of white blood cells was lower
who participated in the study. than 5,000, while after 2 days the number was
increased to be higher than 21,000.
Results  The total number of neutrophils is lower than
Despite the advances in neonatal and perinatal 1,500 or higher than 10,000.
care, neonatal sepsis is still one of the major causes  The IT Ratio ≥ than 0.2.
of mortality and morbidity among infants. In  Degenerative changes in neutrophils (presence
newborns, early warning signs of septicemia are of vacuolization, toxic granulation or Dohle
often mild but its clinical course may be painful. bodies).
Therefore, immediate antimicrobial therapy  Thrombocytopenia ≤ 100,000.
should begin in infants susceptible to sepsis and as Diagram of diagnosis and treatment of sepsis
long as the results of blood culture and in the NICU Section of Al-Zahra Hospital of Tabriz
antimicrobial sensitivity tests are not available, is shown in Figures (2_4).
empirical treatment should begin with the aim of
affecting potential pathogens. To guide the onset of Laboratory tests
empirical treatment, making changes in the Definitive diagnosis is necessary to isolate the
pattern of agent organisms and antimicrobial pathogen from a sterile environment of the body

4 Iranian Journal of Neonatology 2020; 11(1)

Clinical Guideline Adaptation for Treatment of Neonatal Sepsis Based on the Frequency of Microbial Agents Hosseini MB et al

Are there any symptoms of Complete evaluation/ GBS prophylaxis indicated in

neonatal sepsis? antibiotic start one or more of the following:
(1) Mother GBS positive
within preceding 5 weeks,
(2) Unknown GBS status with
one or more intrapartum risk
factors including <37 weeks
gestation, ROM ≥ 18 h or T ≥
Does the mother have 100.4°F (38.0°C),
chorioamnionitis? A (3) GBS bacteriuria during the
current pregnancy.
(4) History of infant with a
previous GBS disease.

Does the mother have GBS Routine care

prophylaxis indication?

Has the mother received

At least 48 h under
antibiotics at least 4 h
observation
before the delivery?

At least 48 h under
≥35 weeks observation
Is the rupture of
membranes less than 18 h?

<35 weeks A

<37 weeks A
Is the rupture of membranes •
≥18 h?

≥37 weeks
B

Figure 2. Diagnosis and treatment of sepsis in the Neonatal Intensive Care Unit Department of Al-Zahra Hospital in Tabriz, Iran

(blood, CSF, and urine) (23). sepsis, a sample of one cc is sufficient (24).
 B/C: Blood culture screening should be  Lumbar puncture: In cases of late sepsis, it
conducted in newborns suspected for neonatal should be performed (19).

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Hosseini MB et al Clinical Guideline Adaptation for Treatment of Neonatal Sepsis Based on the Frequency of Microbial Agents

Figure 3. Chart A

Complete blood count with differential/ C-reactive protein

at age 6-12 h

Antibiotics are not required

To be monitored

The test results are normal

The test results are abnormal with a good general condition

Discharge after 48 h of observation in

Blood culture/ starting antibiotics the absence of any sign of the disease

Blood cultures are negative with a good

general condition

Discharge after 48 h of observation in the

absence of any sign of the disease

Figure 4. Charts B

6 Iranian Journal of Neonatology 2020; 11(1)

Clinical Guideline Adaptation for Treatment of Neonatal Sepsis Based on the Frequency of Microbial Agents Hosseini MB et al

Table 2. Antibiotic treatment protocol at the NICU section of the Alzahra Hospital, Tabriz, Iran
Ampicillin+Gentamicin
Vancomycin+Amikacin
Vancomycin+piperacillin/tazobactam)Tazocin)
Vancomycin+Meropenem
Vancomycin+Meropenem±Amikacin
±Amphotericin B
(Amphotericin is added when there is no response to treatment or any culture is positive for fungi)
NICU: Neonatal Intensive Care Unit

The followings are indications of early sepsis: similar studies, the following antibiotic lines are
1. Positive blood culture. suggested in Table 2.
2. Clinical evidence (clinical symptoms) or The clinical conditions and laboratory results
laboratory evidence strongly suggesting a case should be checked; so that, if the patients clinical
of sepsis. condition did not improve or become worse, the
3. Deterioration of the condition despite the onset given antibiotics should change based on the
of treatment. suggested lines or according to the antibiogram (If
 Urine Analysis: it should be performed in case of available), then a blood culture should be
late sepsis (preferably suprapubic or sterile examined.
catheterization) (25). There is no need to Preferably, the new antibiotics shall be given to
conduct urine analysis in case of early sepsis. the patient within 48 h unless the clinical
condition of the neonate does not allow it. If the
Complete Blood Count with Differential neonate needs antibiotic treatment, 1-hour
 Complete Blood Count with Differential: It treatment should be started as soon as possible
should be carried out 6 to 12 h after birth (if the (19).
case of early sepsis is not certain yet) (24).  The length of the treatment is based on the
The following results are considering to be infection location and the patients clinical
abnormal: response.
1. Leukocyte < 5,000 or > 20,000 (cells/mm³).  Untreated bacterial infections are usually
2. Total neutrophil count of < 1,500 cells/ mm³. treated between 7 to 10 days. (Preferably 10 to
3. I/T RATIO >0.2. 14 days for 32>Gestational Age) (25).
4. Platelet <100,000 cells/ mm³.  Uncomplicated Group B Strep (GBS) Meningitis
No single marker carries the necessary is treated between 14 to 21 days. Other
sensitivity to reject sepsis, the following measures secondary GBS locally-acquired infections
should be performed: (cerebritis, osteomyelitis, endocarditis) need a
 CRP: It should be conducted preferably 6 to 12 h longer treatment time (25).
after birth (the sensitivity increases) (24).  Gram-negative Meningitis is treated for a
 To evaluate the response to CRP 2 treatment minimum of 21 or 14 days after obtaining a
should be conducted after 3 days. negative culture (whichever is longer) (26).
 Chest X-ray: should be performed in infants with  Gram-negative bacteremia is treated after 10 to
respiratory distress. 14 days (25).
 If blood culture is negative and infant is in a good
Treatment general condition, in addition, there is no clinical
According to a study on septic germs or laboratory evidence of infection, the treatment
conducted in the NICU of Alzahra Hospital, the can be stopped within 72 h to 5 days (25).
prevalence of germs in early-onset sepsis is  If the blood culture is negative but the case is
as follows: coagulase-negative staph (38.6%), strongly suspected of sepsis, the treatment
Enterobacter and Klebsiella, and Enterococcus should last for 7 days and if the treatment is not
(10.6% each), Acinetobacter (8.8%). This completed after this period, it should continue
prevalence in LOS, includes coagulase-negative (19).
staph (31%), Acinetobacter (22.3%), and Klebsiella  If there is evidence of Necrotizing enterocolitis,
(14.6%). Therefore, based on the sensitivity Metronidazole should be added to the first and
pattern of the germs and according to the results second lines but the other lines do not require
of antibiogram, antibiotic susceptibility and adding medicines. The antibiotic dosage in this
compliance, and also with regard to the results of guideline line is shown in Table 3.

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Hosseini MB et al Clinical Guideline Adaptation for Treatment of Neonatal Sepsis Based on the Frequency of Microbial Agents

Table 3. Antibiotics dosage

Suggested dosage schedules for antibiotics used in newborns
Antibiotic Route <7 days old 1-3 weeks 4 weeks or more
Ampicillin IV, IM 100q12h 100q8h 100q6h
Dosage (mg/kg) and interval of administration
Weight<1,200 g* Weight 1,200-2,000g Weight>2,000 g
Age 0-4 w Age 0-7 days Age>7 days Age 0-7 days Age>7 days
Amikacin†:
SDD IV, IM 7.5q12h 7.5q12h 7.5q8h 10q12h 10q8h
ODD IV, IM 18q48h 16q36h 15q24h 15q24h 15q24h
Aztreonam IV, IM 30q12h 30q12h 30q8h 30q8h 30q6h
Cefazolin IV, IM 20q12h 20q12h 20q12h 20q12h 20q8h
Cefepime IV, IM 50q12h 50q12h 50q8h 50q12h 50q8h
Cefotaxime IV, IM 50q12h 50q12h 50q8h 50q12h 50q8h
Ceftazidime IV, IM 50q12h 50q12h 50q8h 50q8h 50q8h
Ceftriaxone IV, IM 50q24h 50q24h 50q24h 50q24h 75q24h
Cephalothin IV 20q12h 20q12h 20q8h 20q8h 20q6h
Chloramphenicol† IV, PO 25q24h 25q24h 25q24h 25q24h 25q12h
Ciprofloxacin‡ IV — — 10-20q24h — 20-30q12h
Clindamycin IV, IM, PO 5q12h 5q12h 5q8h 5q8h 5q6h
Erythromycin PO 10q12h 10q12h 10q8h 10q12h 10q8h
Gentamicin†:
ODD IV, IM 5q48h 4q36h 4q24h 4q24h 4q24h
Imipenem IV, IM — 20q12h 20q12h 20q12h 20q8h
Linezolid IV — 10q12h 10q8h 10q12h 10q8h
Methicillin:
Meningitis IV, IM 50q12h 50q12h 50q8h 50q8h 50q6h
Other infections IV, IM 25q12h 25q12h 25q8h 25q8h 25q6h
Metronidazole§ IV, PO 7.5q48h 7.5q24h 7.5q12h 7.5q12h 15q12h
Mezlocillin IV, IM 75q12h 75q12h 75q8h 75q12h 75q8h
Meropenem IV, IM — 20q12h 20q12h 20q12h 20q8h
Nafcillin IV 25q12h 25q12h 25q8h 25q8h 37.5q6h
Netilmicin:
SDD† IV, IM 2.5q18h 2.5q12h 2.5q8h 2.5q12h 2.5q8h
ODD IV, IM Same as for gentamicin
Oxacillin IV, IM 25q12h 25q12h 25q8h 25q8h 37.5q6h
Penicillin G (units):
Meningitis IV 50,000q12h 50,000q12h 50,000q8h 50,000q8h 50,000q6h
Other infections IV 25,000q12h 25,000q12h 25,000q8h 25,000q8h 25,000q6h
Penicillin benzathine (units) IM — 50,000 (one dose) 50,000 (one dose) 50,000 (one dose) 50,000 (one dose)
Penicillin procaine (units) IM 50,000q24h 50,000q24h 50,000q24h 50,000q24h
Piperacillin IV, IM — 50-75q12h 50-75q8h 50-75q8h 50-75q6h
Piperacillin/tazobactam Same as for piperacillin
Rifampin PO, IV — 10q24h 10q24h 10q24h 10q24h
Ticarcillin IV, IM 75q12h 75q12h 75q8h 75q8h 75q6h
Ticarcillin-clavulanate Sameas for ticarcillin
Tobramycin:
SDD† IV, IM 2.5q18h 2q12h 2q8h 2q12h 2q8h
ODD IV, IM Same as for gentamicin
Vancomycin† IV 15q24h 10q12h 10q12h 10q8h 10q8h
IV: Intravenous, IM: Intramuscular, ODD: Once-daily dosing, PO: Per oral, SDD: standard daily dosing

Discussion
The present study showed the stages of a conditions, as well as macro policies of the health
clinical guideline adaptation for treating neonatal system (17).
sepsis. In this study, in addition to considering Currently, in most treatment centers,
the principles of evidence-based practice, all managing neonatal sepsis is based on studies in
the recommendations of the guideline were developed countries. However, due to the social,
integrated with priorities of cultural and social cultural, and geographic differences the patterns

8 Iranian Journal of Neonatology 2020; 11(1)

Clinical Guideline Adaptation for Treatment of Neonatal Sepsis Based on the Frequency of Microbial Agents Hosseini MB et al

causing neonatal sepsis in these treatment centers Manipal, India in 2011, Ampicillin and Gentamicin
are different (5). antibiotics were determined as the first line and
High prevalence of neonatal sepsis is the main Amikacin as the second line of treatment in the
reason behind the need for an appropriate clinical neonatal sepsis treatment guideline (31). The
guide to treat this condition. The main aim of the similarity of their agents with that of our center is
present study was to provide an appropriate the reason for this choice of antibiotics.
clinical guideline, which was in line with the In a study conducted in Shahid Arefian
common microbial agents causing neonatal sepsis Hospital of Urmia, Iran in 2011, the bacteria were
in infants admitted to Alzahra Hospital in Tabriz. the most resistant to Ampicillin and Cefotaxime.
Doctors through using clinical guideline The bacteria were most sensitive to Vancomycin
create an agreement to act in accordance with and Ciprofloxacin. Therefore, these antibiotics are
the proved recommendations and avoid the first line of treatment in their guideline (32).
ineffective interventions. It also provides easy In another study carried out in Mitford Hospital,
and evidence-based monitoring for supervisory Sir Salimullah Medical College, Dhaka, Bangladesh,
systems (27). in 2013, the most susceptible to the mass
Antimicrobial treatments may alter the of Imipenem, Ceftazidime, Ciprofloxacin, and
microbial flora of the body and potentially Amikacin were determined, and these antibiotics
predispose the infant to opportunistic infections, have been identified as a selective medicine in
which may lead to antibiotic-resistant organisms. their guideline (33). The reason for this difference
In a retrospective study, empirical antibiotic in the results is due to the different type of
administration (for over 5 days) in the first week existing agents and their antibiogram.
of life in the VLBW newborns was associated
with an increased incidence of late sepsis. Limitations and strengths
Therefore, since there is no specific consensus Lack of time for finding resources and not
procedure for the experimental antibiotic having access to some full-text articles were
regimen, antibiotic selection for possible considered as limitations of this study.
infectious sepsis should be performed in such a
way that is suitable for organisms with high Conclusion
mortality. Moreover, antibiotic selection should In the present clinical guideline, we tried to
be conducted in accordance with local resistance provide the best evidence-based practices and
patterns (28). recommendations for the clinical treatment
Furthermore, due to increased antibiotic of neonatal sepsis. This guideline is fully
resistance and the chronicity of infectious agents, clear, accessible, and unambiguous; moreover,
antibiotic selection should be carefully performed algorithms, instructions, checklists, and patient
to reduce the antibiotic resistance of bacterial information are its inseparable parts. Employing
agents in NICUs (29). There is no clinical trial this guideline in the treatment of the neonatal
study on finding the best antibiotic regimen. Each sepsis leads to a unified method of treatment
antibiotic has its special benefits and side effects and reduces the risk of antibiotic resistance,
that will be shown over the course of time (30). mortality, and morbidity associated with sepsis.
Therefore, as mentioned, the experimental
antibiotic therapy should be carried out based on Acknowledgments
native epidemiology and antimicrobial resistance This article was derived from a dissertation
pattern in the neonatal sepsis of the society (29). submitted by Dr. Seyed Amir Abbas Sharif to
Instead of the unusual use of broad-spectrum Tabriz University of Medical Sciences, Iran, in
antibiotics that lead to medication resistance, an partial fulfillment of the requirement for the
appropriate guideline should be proposed in Fellowship of Neonatology. The authors wish to
accordance with the microbial agents in the thank the Deputy of Research at Tabriz
society to promote appropriate use of antibiotics University of Medical Sciences and Children's
with lesser treatment duration and fewer Research Center of Tabriz University of Medical
incidences. Sciences, as well as the staff of NICU of Alzahra
In different studies, the antibiotic guideline is Hospital of Tabriz for their support during the
different depending on the type of agent present study.
in different regions, the antibiotic susceptibility
and resistance. For example, in a study conducted Conflicts of interests
in Kasturba Hospital, Kasturba Medical College, None.

9 Iranian Journal of Neonatology 2020; 11(1)

Hosseini MB et al Clinical Guideline Adaptation for Treatment of Neonatal Sepsis Based on the Frequency of Microbial Agents

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