Antibiotic Usage in Neonates - Guidelines and Current practices

Penggunaan antibiotik ada neonatus

M Jeeva Sankar, Jhuma Sankar, Sushma Nangia

From:

Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India and

Department of Pediatrics, …………………………………………

Corresponding Author:

M Jeeva Sankar MD DM

Senior Research Associate

Department of Pediatrics

All India Institute of Medical Sciences

New Delhi.

Email: jeevasankar@gmail.com
Abstract:

Antibiotics are one of the most abused drugs in the neonatal unit. While appropriate usage is definitely helpful,

indiscriminate use of antibiotics could lead to emergence of multidrug resistance in previously susceptible isolates.

Adopting and implementing a rational antibiotic policy would help alleviate this problem to a significant extent. In this

article, we discuss the strategy for formulating a rational antibiotic policy for any neonatal unit. In addition, we also

review the current antibiotic protocol being followed in major neonatal units of the country.
Introduction

Antibiotics often rival oxygen as the most commonly abused drug in any neonatal intensive care unit: historically,

between 11 and 23 non-infected newborns were treated with antibiotics for every one infant with proven sepsis.1

While appropriate usage of antibiotics helps undoubtedly in reducing the risk of deaths secondary to sepsis, their

indiscriminate use can have serious repercussions including selection of multidrug resistant bacterial pathogens,

increased incidence of fungal sepsis, etc. The key strategy in such scenario would be to have a rational antimicrobial

policy that minimizes the use of antibiotics in non-infected neonates without denying it in an infant with sepsis; it also

involves using appropriate antibiotics for an adequate duration in infected neonates.

The goal of this article is to enable the physicians involved in the care of newborns to devise a rational antibiotic

policy for their respective units based on the available information and evidence. To facilitate this process, a brief

review of the existing antibiotic policies in the major neonatal units of the country has been incorporated in the article.

Antibiotic policy in neonatal units of India: A survey

We conducted a quick survey to evaluate the current practices of antibiotic usage in major level 2/3 units across the

country (n=19). This was accomplished by sending a simple questionnaire to the concerned unit chief/consultant of

the respective units. Response was obtained from seventeen units (89.5%). The key findings from the survey are

given below:

 Almost all units (16/17; 94.1%) employ sepsis screen - a panel of tests, albeit in different combinations to

rule out/rule-in sepsis in neonates with risk factors and/or non-specific symptoms

 Less than half of the units (7/17; 41.2%) surveyed use a risk score for identifying the neonates who are at-

risk for early onset sepsis; two units do not use a proper score but enlist the various risk factors and decide

upon further management

 Three-fourth of the units (12/16; 75%) continue to use prophylactic antibiotics for neonates requiring Commented [JS1]: SGRH did not respond to this question

ventilation for respiratory distress syndrome (RDS)

  A combination of third generation cephalosporin with an aminoglycoside (mostly amikacin) is used as the

first line of antibiotic therapy in about one third of the units surveyed (5/16; 31.2%). About half of the units

use piperacillin-tazobactam as the second line agent (7/16; 43.8%), vancomycin as third line, and

meropenem as the reserve drug (8/16 each; 50%)

 About two-third of the surveyed units (12/17; 70.6%) would wait for 48-72 hours before changing to the next

line of antibiotics in case of non-response to the first line

 Most units (13/16; 81.2%) would stop antibiotics within 48-72 hours in a neonate with clinical suspicion of

sepsis but with negative sepsis screen and blood culture and normal CSF

The survey results indicate an overall healthy trend with most units implementing a rational antibiotic policy that is

titrated to the local needs of the unit. Other significant findings from the survey have been provided at the beginning

of each section.

Rational antibiotic usage in neonates

The various issues related to the use of antibiotics in neonatal sepsis can be discussed under the following headings:

A. When to start?

B. What to start?

C. When to stop?

D. What’s the optimum route and dose?

E. Special situations

A. When to start antibiotics?

The decision to start antibiotics is usually dependent upon two factors: whether the infant is symptomatic and/or at-

risk for sepsis and if the diagnostic tests suggest an infectious etiology. Both of these approaches are, however, not

infallible and are prone to errors. Nevertheless, short of other options, we might still have to follow them to decide

upon initiation of antibiotic therapy in a given infant.

Antibiotic therapy in different scenarios:

If the clinical presentation of sepsis is taken as a continuum – with normal newborns at one end and a ‘classical’

presentation at the other, most neonates with suspect or at-risk for sepsis would present somewhere in the middle of

this spectrum; decision-making therefore becomes difficult in most instances (Figure 1).

Figure 1: The spectrum of neonatal sepsis

Normal newborn Suspect or at-risk for sepsis Definite sepsis

Condition Asymptomatic Asymptomatic; Asymptomatic; Symptomatic; Symptomatic;

No risk factor Risk factor+; Risk factor+; Low suspicion High suspicion
Received IP Not received IP
antibiotics antibiotics
Examples Mother with PPROM Prematurity and Respiratory Bulging fontanel
for >7 days on prolonged labor distress; apnea; with seizures,
antibiotics lethargy sclerema, shock ,
DIC
Typical Some cases of EOS Most cases of EOS LOS in preterm Community
presentation VLBW infants; acquired LOS
in Occasional cases
of EOS
(IP, intrapartum; PPROM, preterm premature rupture of membranes; EOS, early onset sepsis; LOS, late onset sepsis)

Scenario 1: Asymptomatic neonate with presence of risk factors

Panel 1: Existing practice in major neonatal units (n=17)

 No treatment: 2 (11.8%)*

 Treat without any sepsis screen: 5 (29.4%)

Commented [JS2]: Please check the SGRH response – it does
 Screen and treat (if positive): 10 (58.8%) not fit into a single category – I have included in the third option;
but it can be included in the first also (no antibiotics) - I am not able
*except preterm and/or VLBW infants to decide.

This scenario typically occurs in the setting of early onset sepsis (EOS) where the mode of infection involves vertical

transmission from the mother’s genital tract. The risk of sepsis in these infants is definitely higher than those without
any risk factor – it varies from 10 to 25 fold for different risk factors.2 Unfortunately, most of the infants who develop

sepsis are asymptomatic at birth; they manifest symptoms usually by 24 (~90%) to 48 hours (~100%).3, 4

Two options are available for management of these infants – observation alone or actively screening with or without

antimicrobial therapy based on the perceived risk.

Observation alone: This approach involves careful monitoring of the infant until (s)he develops one or more

symptoms suggestive of sepsis. Though seems more rational, it is fraught with the danger of missing an occasional

infant who progresses to develop a fulminant disease within hours of presentation. In one study involving about 1300

neonates with risk factors for sepsis, asymptomatic status was found to reduce the probability of sepsis by about

75% (adjusted OR: 0.26; 95% CI: 0.11-0.63); however, 1% of these infants were found to be infected.4 Considering

the facts, some authors have suggested a middle path – observation alone for asymptomatic neonates born at >35

weeks of gestation and antibiotic therapy with or without screening for those born at lesser gestations.5

Screening and/or treatment for sepsis: In this approach, the infants are grouped into different risk categories based

on the presence of risk factors and managed accordingly; for example, neonates who are believed to be at high-risk

(born to mother with chorioamnionitis) are started with antibiotics pending further investigations while those with

moderate risk are treated based on the results of the ‘sepsis screen’.6

It should, however, be remembered that these recommendations are predominantly based on the evidence available

from the industrialized countries where group B streptococcus (GBS) is the predominant pathogen causing EOS.

They may not be applicable to our setting where the incidence of GBS sepsis is very low. Unfortunately, no large

scale studies are available in India that have looked at the effect of various factors on the risk of developing EOS by

using a robust prediction model. A few studies have tried to evaluate the common risk factors and develop a

predictive score for identification of EOS.7 Given the paucity of definitive data, an empirical approach has also been

recommended (Table 1).

Figure 2 outlines the management of any neonate deemed to be at-risk for sepsis based on these parameters.
 Table 1: Examples of predictive ‘risk scores’ for early onset sepsis

Risk score 17 Risk score 28

Risk factor Score 1. Low birth weight or preterm

2. Febrile illness in mother within 2 weeks prior to
1. Birth asphyxia 2 delivery
2. Unclean vaginal examn 2 3. Foul smelling and/or meconium stained amniotic fluid
3. Foul smelling liquor 2 4. Prolonged rupture of membranes >24 h
4. Maternal fever 2 5. More than 3 vaginal examinations during labor
5. Prematurity 3 6. Prolonged and difficult delivery with instrumentation
6. ROM>24 hr 1 7. Perinatal asphyxia (Apgar score <4 at 1 minute) or
7. Duration of labor > 24 hrs 1 difficult resuscitation

Interpretation: Interpretation:
0-3: observe clinically Presence of > 2 risk factors: do sepsis screen
>4: Investigate Foul smelling liquor or presence of three risk factors: start
antibiotics

Figure 2: Management of asymptomatic neonate with risk factors

Asymptomatic neonate with risk factor

Monitor pending report

Sepsis screen, Blood culture

Positive screen Negative screen

Start antibiotics Repeat screen after 12 hrs

Positive culture Negative culture Positive screen Negative screen

Treat for 14 days Treat (duration based Antibiotic till culture report Monitor
on the clinical course)
As one can infer from the figure, the algorithm relies too much on the results of sepsis screen for deciding whether to

start antibiotics or not in a given infant. Though a review on the validity of sepsis screen is beyond the scope of this

article, it suffices here to say that the predictive accuracy of a positive screen is low (about 30-40%).9 Therefore,

many non-infected infants with positive screen are also likely to be treated with antibiotics. On the other hand, the

screen with its high negative predictive value has almost 100% ability to rule-out sepsis in at-risk neonates.6

Most sepsis screen panels combine 4-5 tests, usually a combination of WBC counts and CRP. Two such sepsis

screen panels are given in Table 2. Timing of the sepsis screen is also important – it is suggested that an initial

screen should be obtained not immediately but at least 12 hours after birth.6 Recently, some screen panels have

been modified to include cytokine assays and other adjunctive tests that could be done even in the cord blood so as

to facilitate early diagnosis of sepsis.

Table 2: Examples of sepsis screen

Screen panel 12* Screen panel 28

Test Score
1. Total leukocyte count <7500 or >40000/mm3 1 1. Total leukocyte count <5000/mm3
2. Absolute neutrophil count <1750/mm3 1 2. Absolute neutrophil count <1500/mm3
3. Immature/total neutrophils >0.2 1 3. Immature/total neutrophils >0.2
4. Immature/total neutrophils >0.4 2 4. Micro-ESR >15 mm in 1st hour
5. C-reactive protein >1 mg/dL 1 5. C-reactive protein >1 mg/dL
6. C-reactive protein >5 mg/dL 2

Interpretation: Interpretation:
Screen positive if score is >2 - if two or more tests are positive, infant should be
treated for possible sepsis;
- if none/one test is positive, screen to be repeated
after 12 hours (if clinical suspicion still persists).

Scenario 2: Asymptomatic infant with risk factors; received intrapartum antibiotics

This scenario is particularly relevant in units from industrialized countries where intrapartum (IP) chemoprophylaxis is

routinely administered to mothers with GBS colonization. In India where gram negative bacilli are the major

pathogens responsible for EOS, the effect of such intrapartum prophylaxis, if any, remains largely unknown.

Presently, there is no evidence to suggest that the initial work-up of these infants should in anyway be different from

those who did not receive IP prophylaxis; in one of the few studies that evaluated the risk of EOS among preterm
neonates exposed to intrapartum antibiotics, the independent risk factors found to be associated with sepsis (>3 per

vaginal examinations, chorioamnionitis, birth weight <1500g, gestation <30 weeks, male gender) were not different

from those listed before. However, since the antibiotic prophylaxis could affect the blood culture results, the decision

to stop antibiotic therapy in these infants should be based more on the clinical course than on the negative culture

report (cf. infants who did not receive IP antibiotics).

Scenario 3: Symptomatic neonate

Any neonate with clinical features suggestive of sepsis should be promptly evaluated. The clinical judgment of the

constellation of symptoms and signs should help in deciding about when to start antibiotics immediately and when to

observe and monitor closely followed by treatment if necessary. When the clinical suspicion is low – typical example

is a preterm VLBW neonate developing ‘vague’ symptoms like lethargy, tachycardia or even apnea in the second

week of life – it is prudent to wait until the results of a septic screen and/or blood culture reports are available. Infants

manifesting with symptoms like respiratory distress in the first 24-48 hours of life also fall in this category. A chest x-

ray along with screen results and the presence or absence of perinatal risk factors would help in ruling out sepsis.

In contrast, when the clinical suspicion is high – as in neonates with community acquired sepsis (pneumonia /

meningitis) – antibiotic therapy should be initiated without any delay (Figure 3).

Figure 3: Management of neonate with symptoms suggestive of sepsis

Symptomatic neonate

Low suspicion High suspicion

Positive screen Negative screen Investigate and treat

pending report

Treat for 14 Monitor Progression of

days disease
 B. Choice of antibiotics

Panel 2: Existing practice in major neonatal units

Ampicillin+ 3rd gen.cephal+ Piperacillin- Others

aminoglycoside aminoglyc. tazobactam+
aminoglyc.
EOS with positive 4 (25.0%) 3 (18.8%) 2 (12.5%) Amika alone: 3
sepsis screen (n=16)* (18.8%)
Community acquired 6(40.0%) 5 (33.3%) 2 (13.3%) Co-amoxiclav+
sepsis (n=15)* Aminogly.:1 (6.7%)
Nosocomial sepsis 0 4 (23.5%) 5 (29.4%) Meropenem+
(n=17) amika: 3 (17.6%)
Vancomycin: 3
(17.6%)
No information available from units catering to only extramural or intramural neonates
*

The initial choice of antibiotics for sepsis is almost always empirical because the culture reports would be available

after only 48-72 hours. The antibiotics thus started can either be continued as such or modified based on the culture

report and/or the clinical condition of the infant. Knowledge about the prevalent microbial flora and their

sensitivity/resistance pattern in a particular unit and the common antibiotics used in the neonatal period – their side-

effects and the organisms susceptible as well as resistant to them - are essential to rationalize the empirical antibiotic

therapy for that unit.

Table 3 provides a typical example of an empirical regimen suggested for use in facility settings.10

Table 3: Suggested regimen for first line antibiotic therapy in facility settings*

 Early and late onset sepsis: ampicillin plus gentamicin

 Early onset meningitis: ampicillin plus gentamicin
 Late onset meningitis: ampicillin, gentamicin (or amikacin), and/or cefotaxime
 Suspected staphylococcal sepsis, focal skin, bone, joint infections, omphalitis: methicillin/nafcillin plus
gentamicin

 For sepsis of suspected GI origin: ampicillin, gentamicin/amikacin, plus clindamycin (or piperacillin)
 Nosocomial infection in setting with MRSA: vancomycin plus gentamicin (and/or ceftazidime, if high
prevalence of pseudomonas)
* Source: From the report of WHO meeting to “Explore simplified antimicrobial regimens for the treatment of neonatal sepsis”
 Given that most organisms isolated from Indian units are resistant to both ampicillin and gentamicin11, such regime

cannot be routinely employed in most centers. Instead, a modified empirical regime for different settings based on the

assumed resistance pattern of the common isolates is being provided here (Table 4).

Table 4: Suggested empirical regime for neonatal sepsis in different settings

Examples Septicemia & pneumonia Meningitis

Situations where resistant strains are unlikely Penicillin or Ampicillin Same as for
(e.g. community-acquired pneumonia) plus septicemia/pneumonia
Gentamicin plus
Cefotaxime
Situations where a few strains are likely to be Ampicillin or Cloxacillin Same as for
resistant to common antibiotics plus septicemia/pneumonia
(e.g. nosocomial infections in intermediate care units Gentamicin or Amikacin plus
that cater to stable preterm infants; also in units that Cefotaxime
adhere to rational antibiotic therapy and avoid
indiscriminate use of broad-spectrum antibiotics)
Situations where most of the strains are likely to Cefotaxime or Same as for
be resistant Piperacillin-tazobactam or septicemia/pneumonia
(e.g. nosocomial infections in intensive care units that Ciprofloxacin (but avoid ciprofloxacin)
cater to high-risk, sick infants; also in units that use plus
broad-spectrum antibiotics indiscriminately) Amikacin;

Consider Vancomycin if MRSA is

suspected.
Special situations

 No improvement / worsening of clinical condition Consider reserve antibiotics

despite ‘appropriate’ first-line antibiotic therapy (e.g meropenem, aztreonam,
cefoperazone-sulbactum)
 Sudden outbreak of infections
Based on the source of outbreak and
the suspected/isolated organism (e.g.
if due to MRSA, then use
vancomycin)
(MRSA, methicillin resistant Staphylococcus aureus)

Deciding the first, second, and third line of antibiotics:

 Panel 3: Existing practice in major neonatal units

3rd gen.cephal+ Piperacillin- Fluoroquinol.+ Other s

aminoglycoside tazobactam+ aminoglycoside
aminoglyc.
First line (n=16)* 5 (31.2%) 1 (6.2%) 1 (6.2%) Ampicillin+
Aminogly.:3 (18.8%);
Co-amoxiclav+
Aminogly.:3 (18.8%)
Second line (n=16)* 1 (6.2%) 7 (43.8%) 3 (18.8%) Cefoperazone-sulbactum:
1 (6.2%);
Netilmycin*: 2 (12.5%)
Third line (n=16)* 0 3 (18.8%) 1 (6.2%) Meropenem: 6 (37.5%);
Vancomycin: 8 (50.0%);
Fluconazole: 1 (6.2%)
Reserve (n=16) * 0 1 (6.2%) 1 (6. 2%) Meropenem: 8 (50.0%);
Cefoperazone-sulbactum:
2 (12.5%)
No response obtained from one unit
*

As the data from the National Neonatal Perinatal Database (NNPD 2002-03) shows, most neonatal units in India

would unfortunately fall under the third category with majority of the isolates being resistant to commonly used

antibiotics.11, 12 Therefore, it becomes essential to further elaborate the process of deciding the first line of antibiotics

in these units. In addition, the second and even the third line of drugs have to be pre-decided because of the

extremely low cultutre positive rates in these units (<30%); these antibiotics might have to be used in the event of

‘non-response’ and negative blood cultures.

Given the varied microbial flora and the diverse antimicrobial sensitivity pattern, it is practically impossible to put-forth

a single policy for all the units ; instead, we have tried to lay down broad guidelines for choosing the first line and the

reserve antibiotics for any neonatal unit:

1. First, collect the data on the prevailing flora and their sensitivity pattern of your unit for the previous 6-12

months

2. Decide the first line of antibiotics based on the following principles:

o Identify a narrow-spectrum antibiotic which covers at least 60-70% of the three most common

organisms isolated from the unit. (Though this strategy appears counter-intuitive, it is employed

because the information from a small proportion of infants with culture positive sepsis (<30%) is
 being extrapolated to other neonates for whom no information is available; also, in more than two-

third of the instances, the selected agent would usually work)

o Identify an aminoglycoside to be used with the selected agent for synergistic action – again

following the same principles (in some instances, aminoglycoside alone would suffice)

o Avoid using broad spectrum antimicrobials such as 3rd generation cephalosporins as the first-line

agent (unless the resistance pattern demands such regime). Using antibiotics like piperacillin-

tazobactam might be a better choice because unlike the former, it does not select for extended

spectrum beta lactamase (ESBL) producing gram negative bacilli. Moreover, the combination of

piperacillin-tazobactam and amikacin is effective for suspected pseudomonas sepsis also.

3. Decide the next line of antibiotics based on these principles:

o These antibiotics should be able to cover almost all the organisms isolated in the given unit.

o Further categorization into second/third line and reserve drugs should depend upon other

considerations like cost, spectrum of activity, safety profile, etc.

o In units with high incidence of infections with cloxacillin or methicillin resistant Staphylococcus

aureus (MRSA), vancomycin might have to be considered as a second/third line agent

o Newer antibiotics like aztreonam, imipenem, and meropenem should be reserved for situations

where sensitivity of the isolate justifies their use. Aztreonam has excellent activity against gram-

negative organisms while meropenem is effective against most bacterial pathogens except MRSA

and enterococcus. Imipenem is usually avoided in neonates because of the reported increase in

the risk of seizures after their use.

C. Duration of antibiotic therapy

 Panel 4: Existing practice in major neonatal units

Once cultures 4-7 days 7-13 days 14-20 days 3 weeks or

are sterile (2- more
3 days)
Meningitis* 0 0 0 5 (29.4%) 12 (70.6%)
Culture positive for 0 2 (11.8%) 6 (35.3%) 8 (47.0%) 1 (5.9%)
gram+ve organisms
Culture positive for 0 0 6 (37.5%) 10 (62.5%) 0
gram-ve organisms
(n=16)£
Positive screen, 5 (29.4%) 9 (52.9%) 3 (17.6%) 0 0
negative culture
Risk factors, negative 13 (81.2%) 3 (18.8%)
screen and culture
(n=16)≠
*
Two units use different regimes for meningitis caused by gram+ve and gram-ve organisms (shorter course for
gram+ve)
£
No response from one unit
≠
No antibiotics started in one unit

The decision to discontinue antibiotic therapy is usually based upon the results of blood culture, sepsis screen, CSF

findings and more importantly the clinical course (Table 5).

Table 5: Duration of antibiotic therapy in neonatal sepsis

Diagnosis Duration

Meningitis (with or without positive blood/CSF culture) 21 days

Blood culture positive but no meningitis 14 days

Culture negative but definite clinical sepsis 10-14 days

Culture negative, sepsis screen positive and clinical course 7-10 days
consistent with sepsis

Culture and sepsis screen negative, but clinical course compatible 5-7 days
with sepsis

The above mentioned regime is, however, empirical and not based on any solid evidence. Only a few studies have

looked at the efficacy of a shorter duration of antibiotic therapy. Engle WD showed that a four day antibiotic course

was as effective as a 7-day course in near term neonates with pneumonia.13 Recently, a study from Chandigarh
 found no difference between 7 day and 14 day antibiotic course in culture positive neonatal sepsis; however, the

failure rate was found to be more in infants with S aureus sepsis treated with short course regime.14 Until more robust

evidence is available, the current policy of administering antibiotics for such long periods might have to be continued.

Antibiotic therapy can, however, be stopped after 48-72 hours in those infants who are started on antibiotics for the

presence of perinatal risk factors if the clinical course is not compatible with sepsis and the cultures are sterile.

D. Route and dose of antibiotic therapy

Either intravenous or intramuscular routes are usually preferred while treating neonatal sepsis. Oral antibiotic therapy

is avoided because of the unpredictable absorption and bioavailability especially in seriously ill neonates. Many

community based studies have successfully used oral cotrimoxazole for management of pneumonia.15 Owing to the

paucity of data regarding use of oral antibiotics in hospital settings, it cannot be recommended presently.

The dosage, route, and the frequency of administration of commonly used antimicrobial agents are given in Table 6.

Table 6a: Dosages (mg/kg/dose) of commonly used antimicrobial agents - Aminoglycosides16

Drug Route <29 weeks PMA 30 to 34 weeks PMA >35 weeks PMA

0-7 days 8-28 days 0-7 days 8-28 days 0-7 days 8-28 days
Amikacin IV Infusion over 30 min 18 q48h 15 q36h 18 q36h 15 q24h 15 q24h 15 q24h
Gentamicin IV Infusion over 30 min 5 q48h 4 q36h 4.5 q36h 4 q24h 4 q24h 4 q24h
Netilmicin IV Infusion over 30 min 5 q48h 4 q36h 4.5 q36h 4 q24h 4 q24h 4 q24h
(PMA, postmenstrual age; IV, intravenous)

Table 6b: Dosages (mg/kg/dose) of commonly used antimicrobial agents (other than aminoglycosides) 16
Drug Route <29 weeks PMA 30 to 36 weeks PMA >37 weeks PMA

0-7 days 8-28 days 0-14 days 14-28 days 0-7 days 8-28 days
Ampicillin IV slow push
Meningitis 100 q12h 100 q12h 100 q12h 100 q8h 100 q12h 100 q8h
Others 50 q12h 50 q12h 50 q12h 50 q8h 50 q12h 50 q8h
Cefotaxime IV Infusion over 30 min 50 q12h 50 q12h 50 q12h 50 q8h 50 q12h 50 q8h
Ciprofloxacin 10-20 q24h 10-20 q24h 10-20 q24h 10-20 q12h 10-20 q24h 10-20 q12h
Cloxacillin 50 q12h 50 q8h 50 q12h 50 q8h 50 q 8h 50 q6h
Meropenem
Meningitis/ IV Infusion over 30 min 40 q8h 40 q8h 40 q8h 40 q8h 40 q8h 40 q8h
Pseudomonas sepsis
Sepsis due to other 20 q12h 20 q12h 20 q12h 20 q12h 20 q12h 20 q12h
organisms
Penicillin G
(Units/kg/day) IV Infusion over 30 min
 Meningitis 75,000-100,000 75,000-100,000 75,000-100,000 75,000-100,000 75,000-100,000 75,000-100,000
q12h q12h q12h q8h q12h q8h
Others 25000 -50000 25000 -50000 25000 -50000 25000 -50000 25000 -50000 25000 -50000
q 12h q12h q12h q8h q12h q8h
Piperacillin + IV Infusion over 30 min 50-100 q12h 50-100 q12h 50-100 q12h 50-100 q8h 50-100 q12h 50-100 q8h
tazobactam
Vancomycin
Meningitis IV Infusion over 60 min 15 q18h 15 q12-18h 15 q12h 15 q8h 15 q12h 15 q8h
Others 10 q18h 10 q12-18h 10 q12h 10 q8h 10 q12h 10 q8h
(PMA, postmenstrual age; IV, intravenous)

E. Special situations

Prophylactic antibiotics:

Panel 1: Existing practice in major neonatal units (n=16)*

In neonates ventilated for respiratory distress syndrome:

 No antibiotics: 4 (25%)

 Only amikacin: 2 (12.5%)

 Aminoglycoside+others: 10 (62.5%)
*
No response from one unit

The use of prophylactic antibiotics for infants on IV fluids/TPN, meconium aspiration syndrome, or after exchange

transfusions is not recommended. An exchange transfusion conducted under strict asepsis (single use catheter,

sterile gloves, removal of catheter after the procedure) does not increase the risk of sepsis. As for antibiotic

prophylaxis in ventilated neonates is concerned, there is not enough evidence to either support or refute its use

(Cochrane review).17

Minimizing antibiotic resistance in neonatal units

Recently in his editorial titled ‘The antibiotic crisis’, Isaacs D has pointed out that unlike other countries, the situation

of antibiotic resistance in Indian neonatal units has reached crisis level. 18 The reasons attributed for this phenomenon

include: not taking blood cultures before staring antibiotics, continuing antibiotics even after a negative culture report,

adding more potent broad spectrum antibiotics if the baby remains ‘sick’, and the belief that raised CRP is proof of

sepsis. It is the duty of every physician involved in the care of newborns to develop as well as implement both local
and national guidelines on antibiotic use in neonates and to ensure that the menace of antibiotic resistance does not

continue unabated.
Acknowledgement:

We greatly acknowledge the following experts for their prompt response to the questionnaire on
“Antibiotic usage in neonatal units of India”: Dr Paul VK, Dr Saili A, Dr Ramji S, Dr Mathur NB, Dr….? from
SGRH (New Delhi); Dr ….PGI, Dr Chawla D (Chandigarh), Dr Nanavati R, Dr Gupta G (Mumbai), Dr Mathai,
Dr Vaidya U (Pune), Dr Bhatia (Varanasi), Dr Shenoi A (Bangalore), Dr Jain N (Trivandrum), Dr Murki S
(Hyderabad), Dr Singh A (Kolkata), Dr Jain S (Indore).
References:

1. Philip AG, Hewitt JR. Early diagnosis of neonatal sepsis. Pediatrics 1980;65:1036-41.
2. St Geme JW Jr, Murray DL, Carter J, Hobel CJ, Leake RD, Anthony BF, Thibeault DC, Ross IB, Drage JS.
Perinatal bacterial infection after prolonged rupture of amniotic membranes: an analysis of risk and management. J
Pediatr 1984;104:608-13.
3. Ottolini MC, Lundgren K, Mirkinson LJ, Cason S, Ottolini MG. Utility of complete blood count and blood culture
screening to diagnose neonatal sepsis in the asymptomatic at risk newborn. Pediatr Infect Dis J 2003;22:430-4.
4. Escobar GJ, Li DK, Armstrong MA, et al. Neonatal sepsis workups in infants >/=2000 grams at birth: A population-
based study. Pediatrics 2000;106:256-63.
5. Polin RA, Parravicini E, Regan JA, Taeusch HW. Bacterial sepsis and meningitis. In: Taeusch HW, Ballard RA,
Gleason CA (eds): Avery’s Diseases of the Newborn, 8th ed. Philadelphia, Saunders, 2005, pp.562-4.
6. Gerdes JS. Diagnosis and management of bacterial infections in the neonate. Pediatr Clin North Am 2004;51:939-
59.
7. Singh M, Narang A, Bhakoo ON. Predictive perinatal score in the diagnosis of neonatal sepsis. J Trop Pediatr
1994;40:365-8.
8. Sankar MJ, Agarwal R, Deorari AK, Paul VK. Sepsis in the newborn. Indian J Pediatr 2008;75:261-6.
9. Gerdes JS. Clinicopathologic approach to the diagnosis of neonatal sepsis. Clin Perinatol 1991;18:361-81.
10. Explore simplified antimicrobial regimens for the treatment of neonatal sepsis. WHO/FCH/CAH/04/1/2002.
11. Deorari AK. For the Investigators of National Neonatal perinatal Database. Changing pattern of bacteriologic
profile in neonatal sepsis among intramural babies. J Neonatol 2006; 20: 8-15.
12. National Neonatal Perinatal Database. Report for the year 2002-03. India: National Neonatology Forum; 2004
13. Engle WD, Jackson GL, Sendelbach D, Ford D, Olesen B, Burton KM, et al. Neonatal pneumonia: comparison of
4 vs 7 days of antibiotic therapy in term and near-term infants. J Perinatol 2000;20:421-6.
14. Chowdhary G, Dutta S, Narang A. Randomized controlled trial of 7-Day vs. 14-Day antibiotics for neonatal
sepsis. J Trop Pediatr 2006;52:427-32.
15. Bang AT, Bang RA, Baitule SB, Reddy MH, Deshmukh MD. Effect of home-based neonatal care and
management of sepsis on neonatal mortality: field trial in rural India. Lancet 1999;354:1955-61.
16. Young TE, Magnum B: Neofax®: A manual of Drugs Used in Neonatal Care, ed 20. Montvale, New Jersey:
Thomson Healthcare, USA, 2007.
17. Inglis GD, Jardine LA, Davies MW. Prophylactic antibiotics to reduce morbidity and mortality in ventilated
newborn infants. Cochrane Database Syst Rev 2007;3:CD004338.
18. Isaacs D. Neonatal sepsis: the antibiotic crisis. Indian Pediatr 2005;42:9-13.