Introduction: Antibiotics are the most commonly prescribed medications in neonatal intensive care
units (NICUs). There is increasing evidence that inappropriate or excessive use of
antibiotics in the NICU leads to serious adverse outcomes such as the emergence of
multidrug-resistant organisms linked to endemic or epidemic infections, increased
rates of invasive candidiasis, necrotizing enterocolitis, late-onset sepsis, or death.
NICU is a distinctive place in any hospital due to the variability and fragility of
its patients. It can be challenging for clinicians to determine which infants warrant
empiric antimicrobial therapy for possible infection. Antimicrobial stewardship, as
defined by the Infectious Diseases Society of America, includes interventions targeted
toward the improvement and monitoring of appropriate antimicrobial use by selecting
the most optimal drug regimen, including the type of drug used, dose, duration of
therapy, and route of administration. Eliminating overuse is considered perhaps the
most effective way to improve quality and reduce cost, yet the strategy has largely
been neglected in quality improvement research and interventions. In this study, we
assessed the effectiveness of an intervention that was directed toward restriction
of antibiotic usage in our NICU.
Materials and Methods: This prospective study was conducted in a tertiary level 3 NICU in Chennai from May
2015 to June 2016. We divided the study period into two eras, first 7 months (May
2015–November 2015) before the introduction of intervention, that is, “Antibiotic
Justification Form” and next 7 months (December 2015–June 2016) after the introduction
of intervention. Infants were prospectively enrolled. Infants admitted in era 1 were
labeled as Group A and those admitted in era 2 were labeled as Group B. The antibiotic
policy in era 1 was similar to what we used to follow before this stewardship program.
Institutional ethics committee approval was taken prior to the start of the study.
The antibiotic justification form was devised after discussion with the hospital infection
control (HIC) team. Meropenem, imipenem, teicoplanin, vancomycin, tigecycline, doripenem,
colistin, polymixin B, and caspofungin were labeled as high-end antibiotics or restricted
group. The form needed details such as diagnosis, empirical, or definitive therapy
with justification and signature of the consultant with date and time. The form was
introduced on November 15, 2015, and the nurses and doctors were trained for 15 days
for its usage. The justification form had to be filled within 24 hours of starting
a restricted antimicrobial. The treating consultant and in-charge nurse were notified
of the culture report within 48 to 72 hours by the infection control nurse. The duty
doctor had to give the justification for starting the drug to be countersigned by
the treating consultant. The form was reviewed on day 7 regarding the continuation
of the antibiotic and the justification had to be given for continuation of the same.
Any change of antibiotic within the restricted group also warranted specifying justification.
Monthly review of the forms was done by the HIC committee. Our first-line antibiotics
were ampicillin, piperacillin–tazobactam, and amikacin.
Statistical Analysis: Our estimated incidence of use of restricted antimicrobials prior to the study was
around 45%. To reduce the use of restricted antimicrobials from 45 to 25% with α error
0.05 and power 90%, 398 cases and 398 controls would be required. Student’s t-test and chi-square test were used for continuous and categorical variables, respectively.
Comparison of means and proportions was used wherever appropriate. Relative risk and
mean difference with 95% confidence intervals were calculated. A p-value of less than 0.05 was considered statistically significant.
Results and Discussion: In preintervention period, 429 infants were admitted, whereas in postintervention
period, 428 infants were admitted ([Table 1]). The two groups were comparable in terms of gestational age, diagnoses, mortality,
and sepsis rates. One hundred ninety infants (44.29%) received restricted antimicrobials
in era 1 compared with 150 infants (35.05%) in era 2 (p = 0.005). The total duration of restricted antimicrobials significantly reduced from
13.78 to 9.9 days in postintervention period (p = < 0.0001). Fifty-six infants (29.47%) were de-escalated from restricted group
to first-line antibiotics in era 1 compared with 90 infants (80.36%) in era 2 (p = < 0.0001). The duration of first-line antibiotics also significantly reduced from
9.06 to 4.8 days (p = < 0.0001). However, there was no difference in number of infants started on any
antibiotic in both the groups (p = 0.1). We also analyzed the usage of our first-line antibiotics along with the reasons
for empirical restricted group in both the eras. There was no statistically significant
difference in usage of ampicillin, piperacillin–tazobactam, and amikacin between the
two groups. The most common cause for usage of high-end antibiotics in Group A was
clinician’s decision (p = < 0.0001), whereas in Group B, it was worsening sepsis in spite of empirical therapy
(p = < 0.0001).
Conclusion: Introduction of antibiotic justification form helps in reducing the usage of restricted
anti microbials along with rapid de-escalation and thus reducing the duration of these
higher end antibiotics attributed to the awareness created among the clinicians.
Keywords: antibiotic overuse, de-escalation, justification form, resistance
Table 1 Comparison of baseline characteristics between Groups A and B
|
Characteristics
|
Group A (May 2015–November 2015)
|
Group B (December 2015–June 2016)
|
p-Value
|
|
Total admissions
|
429 (50.05%)
|
428 (49.94%)
|
0.97
|
|
Number of outborn infants
|
316 (73.66%)
|
324 (75.7%)
|
0.55
|
|
Male
|
235 (54.77%)
|
240 (56.07%)
|
0.7
|
|
Gestational age in weeks (mean)
|
34.38 (0.9)
|
34.33 (0.7)
|
0.36
|
|
Ventilated
|
90 (20.97%)
|
81 (18.93%)
|
0.45
|
|
CPAP
|
66 (15.38%)
|
58 (13.55%)
|
0.44
|
|
RDS
|
95 (22.14%)
|
85 (19.86%)
|
0.41
|
|
MAS
|
20 (4.66%)
|
19 (4.44%)
|
0.88
|
|
Asphyxia
|
22 (5.13%)
|
19 (4.44%)
|
0.63
|
|
Culture positive sepsis
|
18 (4.19%)
|
14 (3.27%)
|
0.48
|
|
Surgical
|
8 (1.86%)
|
6 (1.4%)
|
0.59
|
|
Deaths
|
10 (2.33%)
|
12 (2.8%)
|
0.66
|
Abbreviations: CPAP, continuous positive airway pressure; MAS, Macrophage activation
syndrome; RDS, respiratory distress syndrome.
