Antibiotic Justification Form to Restrict Antimicrobial Use in a Tertiary Care Neonatal Unit in South India: A Prospective, Before–After, Interventional Study

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.