Drug Resistance in Gram Negative Rods in Patients Admitted to a Pediatric Hospital

Background: Frequent use of antibiotics (Abx) has been associated with the development of bacterial resistance.  Extensive reliance on broad-spectrum Abx has led to increasing resistance rates in adults, particularly among gram-negative rods (GNR). Data in children, however, remains limited, particularly for fluoroquinolones (FQs).

Objective: To describe resistance patterns in A. baumannii (AB), C. freundii (CitF), E. coli (EC), K. pneumoniae (KP), and P. aeruginosa (PA) isolates to FQs, ceftazidime (CAZ), pipericillin-tazobactam (PTZ), and meropenem (MER) from 2003-2009 and to assess whether recent trends in inpatient Abx use impacted GNR drug resistance.

Methods: Annual Abx susceptibility reports were used to determine the percentage of resistant isolates at our large children’s hospital for each organism to various Abxs from 2003-09.  Days (d) of Abx therapy per 1000 patient (pt) d for different drugs were available for 2007 – 09 and were compared to GNR resistance rates over the same time.

Results: From 2003-09, overall GNR resistance decreased for PTZ (10.3 to 6.6%, p = 0.02), while resistance to CAZ (14 to 11%, p = 0.33) and MER remained stable (7%).  From 2003-09 FQ resistance increased among all GNR (from 10.8 to 14.6%, p = 0.03).  FQ resistance was highest in AB (11 – 36%) followed by PA (8 – 18%) and EC (4 – 13%) and these increases were significant for AB (p = 0.04) and EC (p = 0.01), but not for PA (p = 0.11). Although variations occurred from year to year, FQ-resistance rates of PA isolates from patients without cystic fibrosis (CF) exceeded those of CF patients in 2009 (28 vs. 12%, p <0.01).  Inpatient FQ use varied between 9.7 – 13.6 d of Abx therapy per 1000 pt d without any correlation with FQ resistance. With intensification of antibiotic utilization review over the past 3 years, use of PTZ (29.5 to 16.4 d of Abx therapy per 1000 pt d) and MER (33.6 to 21.5 d of Abx therapy per 1000 pt d) decreased while use of CAZ increased (42.6 to 46.6 d of Abx therapy per 1000 pt d). Despite the decline in the use of PTZ and MER and the increase in CAZ use, no statistically significant change in resistance rates was noted for any of these Abxs against any of the GNR for 2007-09.

Conclusions: GNR resistance rates decreased for PTZ, but increased for FQs from 2003 – 09.  Much of the increase in FQ resistance was driven by resistance rate increases in AB and EC.  In 2009 the FQ resistance rate among PA from non-CF patients exceeded that of isolates from CF patients. No statistically significant change in antibiotic resistance was noted for any GNR by shifting Abx use from PTZ and MER to CAZ.