Repeat blood cultures in children with persistent fever and neutropenia: Diagnostic and clinical implications.

BACKGROUND: Repeat blood cultures are frequently obtained in children with persistent fever and neutropenia (FN), but their clinical impact is uncertain. METHODS: We identified children with persistent FN in the context of hematologic malignancy or hematopoietic stem cell transplantation from July 2006 to June 2012. For each episode, we reviewed blood cultures to determine the yield of true positive and false positive results. We then examined episode-level and culture-level predictors to determine factors associated with new bloodstream infections (BSI). RESULTS: Among 135 children who met inclusion criteria, there were 184 persistent FN episodes, during which 17 new BSI were diagnosed after the first 24 hr of fever (9.2%; 95% CI 5.4-15.3%). After the first 24 hr, the incidence of new BSI was 1.5% (95% CI 1.0-2.4%) per day and the incidence of blood culture contamination was 1.1% (95% CI 0.6-2.1%) per day. Of 17 new BSI identified, 14 (82%) required changes in therapy, while all 12 contaminant blood cultures were followed by additional antibiotic therapy. Increased odds of new BSI were associated with a history of BSI within 30 days of the episode (OR 5.18; 95% CI 1.29-20.8) and increasing time between recurrent fevers (OR 1.29; 95% CI 1.06-1.57). CONCLUSIONS: Repeat blood cultures have an important role in diagnosing new BSI and directing therapy in children with persistent FN. The current strategy could be improved by reducing the frequency of blood cultures after the first 24 hr, and targeting repeat cultures by risk.

Treatment of pediatric refractory coccidioidomycosis with combination voriconazole and caspofungin: a retrospective case series.

BACKGROUND: Coccidioidomycosis is a spectrum of diseases caused by the dimorphic fungi Coccidioides. Current regimens for severe or disseminated disease include fluconazole, itraconazole, or amphotericin; newer triazoles (ie, voriconazole, posaconazole) have been demonstrated to be useful in refractory disease. Previous reported experience with combination triazole and caspofungin therapy has been very limited; however, the utility of this combination for treatment of other invasive fungal diseases suggests potential benefit in refractory coccidioidomycosis. METHODS: We conducted a retrospective review of 9 pediatric patients treated with combination voriconazole and caspofungin (V/C) salvage therapy for refractory coccidioidomycosis at two children's hospitals between January 2000 and June 2012. RESULTS: Nine children with refractory coccidioidomycosis were treated with V/C salvage therapy after failing conventional therapy consisting of a triazole, amphotericin B, or a combination of both. Eight of the 9 patients are currently in remission; 1 patient with central nervous system involvement continues to progress. CONCLUSIONS: We report our positive clinical experience treating medically refractory coccidioidomycosis in the pediatric population with concurrent voriconazole and caspofungin therapy. Additional in vitro and in vivo evaluations are warranted to support the role of V/C salvage therapy for refractory coccidioidomycosis.

Development of herpes simplex virus stomatitis during receipt of cidofovir therapy.

We report 3 children who, after undergoing hematopoietic stem cell transplant, developed herpes simplex virus (HSV) stomatitis while receiving weekly cidofovir as preemptive treatment for cytomegalovirus infection. All patients responded well to treatment with either acyclovir or ganciclovir. Despite the in vitro susceptibility of HSV to cidofovir, once-weekly treatment with this agent may not be adequate prophylaxis in pediatric patients.

Utility of DNA microarrays for detection of viruses in acute respiratory tract infections in children.

OBJECTIVE: To assess the utility of a panviral DNA microarray platform (Virochip) in the detection of viruses associated with pediatric respiratory tract infections (RTIs). STUDY DESIGN: The Virochip was compared with conventional direct fluorescent antibody (DFA)- and polymerase chain reaction (PCR)-based testing for the detection of respiratory viruses in 278 consecutive nasopharyngeal aspirate samples from 222 children. RESULTS: The Virochip was superior in performance to DFA, showing a 19% increase in the detection of 7 respiratory viruses included in standard DFA panels, and was similar to virus-specific PCR (sensitivity, 85% to 90%; specificity, >/=99%; positive predictive value, 94% to 96%; negative predictive value, 97% to 98%) in the detection of respiratory syncytial virus, influenza A, and rhinoviruses/enteroviruses. The Virochip also detected viruses not routinely tested for or missed by DFA and PCR, as well as double infections and infections in critically ill patients that DFA failed to detect. CONCLUSIONS: Given its favorable sensitivity and specificity profile and expanded spectrum for detection, microarray-based viral testing holds promise for clinical diagnosis of pediatric RTIs.

Safe and Effective Prophylaxis with Bimonthly Intravenous Pentamidine in the Pediatric Hematopoietic Stem Cell Transplant Population.

BACKGROUND: Without prophylaxis, Pneumocystis jiroveci pneumonia (PCP) develops in 5%-15% of pediatric hematopoietic stem cell transplant (HCT) patients with mortality above 50%. Trimethoprim-sulfamethoxazole is a standard PCP prophylaxis; pentamidine is frequently used as second-line prophylaxis because of trimethoprim-sulfamethoxazole's potential for cytopenias. Monthly intravenous (IV) pentamidine has variable efficacy with PCP infection rates of 0%-10% in pediatric patients, and higher breakthrough rates in those younger than 2 years. We hypothesized that bimonthly (twice monthly) pentamidine might have equivalent safety and improved efficacy; therefore, we conducted a retrospective analysis of bimonthly pentamidine PCP prophylaxis. METHODS: We retrospectively reviewed records of all pediatric HCT patients who received bimonthly IV pentamidine between December 2006 and June 2013, and collected data regarding demographics, clinical course, prophylaxis rationale, laboratory values and adverse events. RESULTS: Between December 2006 and June 2013, 111 pediatric HCT patients received bimonthly IV pentamidine (574 doses, 8758 patient-days); 31 patients were younger than 2 years at initiation. In the majority (53% of courses), pentamidine was initiated because of cytopenias. Fourteen patients (12.6% of patients, 2.4% of doses) experienced a side-effect prompting discontinuation, including 3 patients with infusion-related hypotension/anaphylaxis and 3 with acute pancreatic dysfunction. No patients [0% (95% confidence interval: 0-3.2)] developed PCP during or after bimonthly IV pentamidine prophylaxis. CONCLUSIONS: Bimonthly IV pentamidine for PCP prophylaxis in the HCT pediatric population has comparable safety to monthly IV pentamidine and was highly effective, including in the very young. Bimonthly IV pentamidine should be considered in pediatric patients as second-line PCP prophylaxis.

Risk factors and risk adjustment for surgical site infections in pediatric cardiothoracic surgery patients.

BACKGROUND: The complexity of congenital cardiac defects and the aggressive medical management required to support patients through their recovery place children at high risk for surgical site infection (SSI). METHODS: We conducted a retrospective review of children undergoing cardiothoracic surgery at a tertiary care referral center between January 1, 2000, and June 30, 2001. Preoperative, intraoperative, and postoperative data were assessed by multivariate analysis. RESULTS: Of 726 surgical procedures performed in 626 patients, SSIs occurred after 46 procedures performed in 46 patients (6.3%). Infections were superficial (n = 22; 47.8%), deep tissue (n = 7; 15.2%), or organ space (n = 17; 37.0%), including 5 episodes of mediastinitis. Median time to SSI was 10 days; 36% of the infections were identified after discharge. On multivariate analysis, children with SSIs were more likely to have been <30 days old (odds ratio [OR], 2.9; 95% confidence interval [CI], 1.2-70), to have a perioperative medical device, and to use parenteral nutrition (OR, 3.3; 95% CI, 1.4-7.9). Multiple severity of illness scores, the Risk Adjustment for Congenital Heart Surgery (RACHS-1) category, and longer duration of postoperative antimicrobials were not associated with SSI. CONCLUSION: The use of perioperative medical interventions increases the risk of SSI in young children after cardiac surgery. Prolonged postoperative courses of antimicrobials should be avoided in the absence of documented infection.

Antibiotic selection for purulent skin and soft-tissue infections in ambulatory care: a decision-analytic approach.

OBJECTIVE: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has caused a nationwide epidemic of skin and soft-tissue infections in ambulatory pediatrics. Antibiotic treatment recommendations suggest incorporating local epidemiology for the prevalence of CA-MRSA. We sought to identify the antibiotic strategy with the highest probability of activity and to identify threshold values for epidemiologic variables including bacterial prevalence and antibiotic resistance. METHODS: We used decision analysis to evaluate 3 empiric antibiotic strategies: clindamycin, trimethoprim/sulfamethoxazole (T/S), and cephalexin. We calculated the probability of activity against the bacteria causing the infection (CA-MRSA, methicillin-sensitive S. aureus and group A Streptococcus [GAS]) by incorporating estimates of prevalence and antibiotic resistance to determine the optimal strategy. Sensitivity analysis was used to identify thresholds for prevalence and antibiotic resistance where 2 strategies were equal. RESULTS: Clindamycin (0.95) and T/S (0.89) had substantially higher probability of activity than cephalexin (0.28) using baseline estimates for bacterial prevalence and antibiotic resistance. Cephalexin was the optimal antibiotic only when CA-MRSA prevalence was <10%. The probability of activity for clindamycin and T/S was highly sensitive to changes in the values for bacterial prevalence (both CA-MRSA and GAS) and CA-MRSA resistance to clindamycin. CONCLUSIONS: Empiric treatment of skin and soft-tissue infections with either clindamycin or T/S maximizes the probability that the antibiotic will be active when CA-MRSA prevalence is >10%. Deciding between T/S and clindamycin requires consideration of antibiotic resistance and prevalence of GAS. This model can be customized to local communities and illustrates the importance of ongoing epidemiologic surveillance in primary care settings.