Outcomes of Children with Osteoarticular Infections Treated with Trimethoprim-Sulfamethoxazole versus Clindamycin
Authors: Garcia Hannah , Duvall Lydia , Tyte Julian , Kussin Michelle , Wood James B 
Published: November 2023

Abstract

Background
Early transition to oral antibiotic therapy for the treatment of children with osteoarticular infections (OAI; osteomyelitis [OM], septic arthritis [SA]) has become increasingly common, yet the choice of optimal regimen remains a challenge. With increasing resistance, poor palatability and reported allergies to commonly used oral antibiotics, the treatment options for children with OAI are limited. Trimethoprim-sulfamethoxazole (TMP-SMX) is a commonly used antibiotic, with activity against frequently encountered pathogens causing OAI, yet data regarding outcomes of children with OAI treated with TMP-SMX is limited. We sought to describe the characteristics and outcomes of children with OAI treated with TMP-SMX compared to clindamycin.

Methods
Records of children &lt;18 years old, admitted to Riley Hospital for Children (Indianapolis, IN) between January 2010 to June 2021 for acute OAI were reviewed. Patients were identified by ICD-9/10 codes and an order for TMP-SMX or clindamycin. Patients were excluded if they did not receive TMP-SMX or clindamycin as their primary oral treatment of OAI, had symptoms &gt;30 days, had a hardware associated infection, were immunocompromised or had an alternative diagnosis. Demographic, clinical, and outpatient/follow up data were recorded. Treatment was considered successful if the patient completed treatment with the discharge oral antibiotic (either TMP-SMX or clindamycin), and there was no evidence of infection at the end therapy. Treatment failure was defined as inability to tolerate the medication, development of an infection related complication, recurrent or chronic osteomyelitis. Additionally, significant adverse drug events (ADEs) were recorded.

Results
A total of 148 children met eligibility criteria (30 TMP-SMX and 118 clindamycin). Demographic and clinical characteristics are highlighted in Table 1. Children receiving TMP/SMX were younger (1.75 years) compared to those receiving clindamycin (7 years). Osteomyelitis was the most common infection type in both groups (47% in the TMP/SMX group vs. 48% in the clindamycin group). Staphylococcus aureus was the causative pathogen in 37% and 49%, while no organism was recovered in 57% and 43% in the TMP/SMX and clindamycin groups, respectively. Complications during hospitalization occurred in 13% in the TMP/SMX group, compared to 16% in the clindamycin group. The median dose of TMP-SMX was 13.4 mg/kg/day (IQR 11.3-14.9) and 38.7 mg/kg/day (IQR 33.4-40.2) for clindamycin.
There was no difference in adverse drug events between the two groups with 2 patients (7%) in the TMP/SMX group developing an ADE compared to 13 patients (11%) in the clindamycin group (p=0.74, OR 0.58 [95% CI: 0.12-2.51]). Five (17%) of patients in the TMP/SMX group and 12 (10%) in the clindamycin group were lost to follow up. Of the patients that completed follow-up, there was no difference in treatment success with 84% (21 of 25) in the TMP/SMX and 92% (97 of 106) in the clindamycin group (p=0.27, OR 0.49 [95% CI: 0.15-1.54]) being successfully treated.

Conclusions
TMP-SMX was well tolerated and not associated with higher odds of treatment failure compared to clindamycin. A larger, prospective, randomized, comparative effectiveness study to control for potential confounding variables, and detect smaller, yet potentially clinically relevant outcome differences is warranted.