Association of Empiric Antibiotic Regimen Discordance With 30-Day Mortality in Neonatal and Pediatric Bloodstream Infection-A Global Retrospective Cohort Study.

2020

2020 Dec 21

1532-0987

<p><strong>BACKGROUND: </strong>While there have been studies in adults reporting discordant empiric antibiotic treatment associated with poor outcomes, this area is relatively unexplored in children and neonates despite evidence of increasing resistance to recommended first-line treatment regimens.</p>

<p><strong>METHODS: </strong>Patient characteristics, antibiotic treatment, microbiology, and 30-day all-cause outcome from children &lt;18 years with blood-culture-confirmed bacterial bloodstream infections (BSI) were collected anonymously using REDCap™ through the Global Antibiotic Prescribing and Resistance in Neonates and Children network from February 2016 to February 2017. Concordance of early empiric antibiotic treatment was determined using European Committee on Antimicrobial Susceptibility Testing interpretive guidelines. The relationship between concordance of empiric regimen and 30-day mortality was investigated using multivariable regression.</p>

<p><strong>RESULTS: </strong>Four hundred fifty-two children with blood-culture-positive BSI receiving early empiric antibiotics were reported by 25 hospitals in 19 countries. Sixty percent (273/452) were under the age of 2 years. S. aureus, E. coli, and Klebsiella spp. were the most common isolates, and there were 158 unique empiric regimens prescribed. Fifteen percent (69/452) of patients received a discordant regimen, and 7.7% (35/452) died. Six percent (23/383) of patients with concordant regimen died compared with 17.4% (12/69) of patients with discordant regimen. Adjusting for age, sex, presence of comorbidity, unit type, hospital-acquired infections, and Gram stain, the odds of 30-day mortality were 2.9 (95% confidence interval: 1.2-7.0; P = 0.015) for patients receiving discordant early empiric antibiotics.</p>

<p><strong>CONCLUSIONS: </strong>Odds of mortality in confirmed pediatric BSI are nearly 3-fold higher for patients receiving a discordant early empiric antibiotic regimen. The impact of improved concordance of early empiric treatment on mortality, particularly in critically ill patients, needs further evaluation.</p>

10.1097/INF.0000000000002910

Pediatr Infect Dis J

33395208

Comparative Effectiveness of Ceftriaxone plus Metronidazole versus Anti-Pseudomonal Antibiotics for Perforated Appendicitis in Children.

2019

399-405

2019 Jul

1557-8674

<p>Appendicitis is the most common pediatric surgical emergency and one of the most common indications for antibiotic use in hospitalized children. The antibiotic choice differs widely across children's hospitals, and the optimal regimen for perforated appendicitis remains unclear. We conducted a retrospective cohort study comparing initial antibiotic regimens for perforated appendicitis at a large tertiary-care children's hospital. Children hospitalized between January 2011 and March 2015 who underwent surgery for perforated appendicitis were identified by ICD-9 codes with confirmation by chart review. Patients were excluded if they had been admitted ≥48 hours prior to diagnosis, had a history of appendicitis, received inotropic agents, were immunocompromised, or were given an antibiotic regimen other than ceftriaxone plus metronidazole (CTX/MTZ) or an anti-pseudomonal drug (cefepime, piperacillin/tazobactam, ciprofloxacin, imipenem, or meropenem) within the first two days after diagnosis. The primary outcome of interest was post-operative complications, defined as development of an incisional infection or abscess within six weeks of hospital discharge. Of the 353 children who met the inclusion criteria, 252 (71%) received CTX/MTZ and the others received an anti-pseudomonal regimen. A post-operative complication occurred in 37 (14.7%) of the CTX/MTZ group versus 18 (17.8%) of the anti-pseudomonal group. Antibiotic-related complications occurred in 4.4% of children on CTX/MTZ and 6.9% of children on anti-pseudomonal antibiotics (p = 0.32). In a multivariable logistic regression model adjusting for sex, age, ethnicity, and duration of symptoms prior to presentation, the adjusted odds ratio for post-operative complications in children receiving anti-pseudomonal antibiotics was 1.25 (95% confidence interval 0.66-2.40). Post-operative complication rates did not differ for children treated with CTX/MTZ versus a broader-spectrum regimen.</p>

10.1089/sur.2018.234

Surg Infect (Larchmt)

30874482

Clinical Impact of Malaria Rapid Diagnostic Testing at a US Children's Hospital.

2019

2019 Apr 16

2048-7207

<p><strong>BACKGROUND: </strong>Children who develop malaria after returning to a setting in which the disease is not endemic are at high risk for critical delays in diagnosis and initiation of antimalarial therapy. We assessed the clinical impact of the implementation of malaria rapid diagnostic testing (RDT) on the management of children with malaria at an urban US children's hospital that serves a large immigrant population.</p>

<p><strong>METHODS: </strong>This was a retrospective cohort study of all children diagnosed with laboratory-confirmed malaria at the Children's Hospital of Philadelphia (CHOP) between 2000 and 2014. RDT using a US Food and Drug Administration-approved immunochromatographic assay was introduced at CHOP on August 1, 2007. We compared clinical management and outcomes of patients with malaria diagnosed before and after RDT introduction.</p>

<p><strong>RESULTS: </strong>We analyzed 82 pediatric malaria cases (32 before and 50 after RDT implementation). The majority of these patients had traveled to West Africa (91.5%) and were infected with Plasmodium falciparum (80.5%). The mean time to a positive result decreased from 10.4 to 0.9 hours (P &lt; .001) after the introduction of RDT for patients with P falciparum. The mean time to antimalarial therapy decreased from 13.1 to 6.9 hours (P =; .023) in hospitalized patients. We found no significant reduction in the mean number of clinical signs of severe malaria between 0 and 48 hours of hospitalization and no difference in the need for exchange transfusion, time to resolution of parasitemia, or length of hospital stay.</p>

<p><strong>CONCLUSIONS: </strong>Implementation of RDT for malaria was associated with shorter times to malaria diagnosis and initiation of antimalarial therapy. The results of this study support RDT in the optimal management of patients with malaria who present in settings in which the disease is not endemic.</p>

10.1093/jpids/piz022

J Pediatric Infect Dis Soc

30989220

Clinical Features and Outcomes of Children with Culture-Negative Septic Arthritis.

2018

2018 Apr 30

2048-7207

<p><strong>Background: </strong>Septic arthritis is a serious infection, but the results of blood and joint fluid cultures are often negative in children. We describe here the clinical features and management of culture-negative septic arthritis in children at our hospital and their outcomes.</p>

<p><strong>Methods: </strong>We performed a retrospective review of a cohort of children with septic arthritis who were hospitalized at Children's Hospital of Philadelphia between January 2002 and December 2014. Culture-negative septic arthritis was defined as a joint white blood cell count of &gt;50000/μL with associated symptoms, a clinical diagnosis of septic arthritis, and a negative culture result. Children with pretreatment, an intensive case unit admission, Lyme arthritis, immunodeficiency, or surgical hardware were excluded. Treatment failure included a change in antibiotics, surgery, and/or reevaluation because of a lack of improvement/worsening.</p>

<p><strong>Results: </strong>We identified 157 children with septic arthritis. The patients with concurrent osteomyelitis (n = 28) had higher inflammatory marker levels at presentation, had a longer duration of symptoms (median, 4.5 vs 3 days, respectively; P &lt; .001), and more often had bacteremia (46.4% vs 6.2%, respectively; P &lt; .001). Among children with septic arthritis without associated osteomyelitis, 69% (89 of 129) had negative culture results. These children had lower C-reactive protein levels (median, 4.0 vs 7.3 mg/dL, respectively; P = .001) and erythrocyte sedimentation rates (median, 39 vs 51 mm/hour, respectively; P = .01) at admission and less often had foot/ankle involvement (P = .02). Among the children with culture-negative septic arthritis, the inpatient treatment failure rate was 9.1%, and treatment failure was more common in boys than in girls (17.1% vs 3.8%, respectively; P = .03). We found no association between treatment failure and empiric antibiotics or patient age. No outpatient treatment failures occurred during the 6-month follow-up period, although 17% of the children discharged with a peripherally inserted central catheter line experienced complications, including 3 with bacteremia.</p>

<p><strong>Conclusions: </strong>The majority of septic arthritis infections at our institution were culture negative. Among patients with culture-negative infection, empiric antibiotics failed for 9% and necessitated a change in therapy. More sensitive diagnostic testing should be implemented to elucidate the causes of culture-negative septic arthritis in children.</p>

10.1093/jpids/piy034

J Pediatric Infect Dis Soc

29718310