<p>Efavirenz is a non-nucleoside reverse transcriptase inhibitor (NNRTI), used for the treatment of human immunodeficiency virus (HIV)-1 infection. Approved by the US Food and Drug Administration in 1998, its indication was recently extended to include children as young as 3 months of age. The World Health Organization and many national guidelines consider efavirenz to be the preferred NNRTI for first-line treatment of children over the age of 3 years. Clinical outcomes of patients on three-drug antiretroviral regimens which include efavirenz are as good as or better than those for patients on all other currently approved HIV medications. Efavirenz is dosed once daily and has pediatric-friendly formulations. It is usually well tolerated, with central nervous system side effects being of greatest concern. Efavirenz increases the risk of neural tube defects in nonhuman primates and therefore its use during the first trimester of pregnancy is limited in some settings. With minimal interactions with antituberculous drugs, efavirenz is preferred for use among patients with HIV/tuberculosis coinfection. Efavirenz can be rendered inactive by a single point mutation in the reverse transcriptase enzyme. Newer NNRTI drugs such as etravirine, not yet approved for use in children under the age of 6 years, may maintain their activity following development of efavirenz resistance. This review highlights key points from the existing literature regarding the use of efavirenz in children and suggests directions for future investigation.</p>

<p><strong>BACKGROUND: </strong>Bloodstream infection is a major cause of morbidity and mortality. Much of our understanding of the epidemiology and resistance patterns of bloodstream infections comes from studies of hospitalized adults.</p>

<p><strong>METHODS: </strong>We evaluated the epidemiology and antimicrobial resistance of bloodstream infections occurring during an 11-year period in a large, tertiary care children's hospital in the US. All positive blood cultures were identified retrospectively from clinical microbiology laboratory records. We excluded repeat positive cultures with the same organism from the same patient within 30 days and polymicrobial infections.</p>

<p><strong>RESULTS: </strong>We identified 8196 unique episodes of monomicrobial bacteremia in 5508 patients. Overall, 46% were community onset, 72% were Gram-positive bacteria, 22% Gram-negative bacteria and 5% Candida spp. Coagulase negative Staphylococcus was the most common isolated organism. ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.) accounted for 20% of episodes. No S. aureus isolate was resistant to vancomycin or linezolid, and no increase in vancomycin minimum inhibitory concentration among methicillin-resistant S. aureus was observed during the study period. Clinically significant increases in vancomycin-resistant Enterococcus, ceftazidime-resistant P. aeruginosa or carbapenem-resistant Enterobacteriaceae were not observed during the study period; however, rates of methicillin-resistant S. aureus increased over time (P &lt; 0.01).</p>

<p><strong>CONCLUSIONS: </strong>Gram-positive and ESKAPE organisms are leading causes of bacteremia in hospitalized children. Although antimicrobial resistance patterns were favorable compared with prior reports of hospitalized adults, multicenter studies with continuous surveillance are needed to identify trends in the emergence of antimicrobial resistance in this setting.</p>

<p>Frontline clinicians caring for hospitalized children typically knew the indication for antimicrobial therapy but less often knew the current day or planned duration of therapy or of plans for intravenous to oral conversion. Night shift clinicians were less likely to know day of therapy and duration of therapy than day shift clinicians caring for the same patients.</p>

<p>We described 1035 pediatric hospitalizations with daptomycin use in 794 patients since 2004. Daptomycin use was uncommon but increased over time. A minority of hospitals accounted for the majority of use. This variability of daptomycin use highlights the need for future studies to assess the efficacy and safety of daptomycin in children.</p>

<p>Legionnaire disease (LD) is infrequently considered in the differential diagnoses for hospital- and community-acquired pneumonia in pediatrics. We report a case of Legionnaire disease in a 19-year-old male with aplastic anemia after bone marrow transplant, who was being treated in a children's hospital. Severe, refractory pulmonary disease necessitated pneumonectomy to control the infection.</p>

<p>Acute bacterial skin and skin structure infections (SSSIs) are among the most common bacterial infections in children. The medical burden of SSSIs, particularly abscesses, has increased nationwide since the emergence of community-acquired methicillin-resistant Staphylococcus aureus. SSSIs represent a wide spectrum of disease severity. Prompt recognition, timely institution of appropriate therapy, and judicious antimicrobial use optimize patient outcomes. For abscesses, incision and drainage are paramount and might avoid the need for antibiotic treatment in uncomplicated cases. If indicated, empiric antimicrobial therapy should target Streptococcus pyogenes for nonpurulent SSSIs, such as uncomplicated cellulitis, and S aureus for purulent SSSIs such as abscesses.</p>

<p>We report a case of Candida krusei arthritis in an adolescent with secondary acute myelogenous leukemia, who underwent an allogeneic bone marrow transplant complicated by C. krusei fungemia 4 months before her presentation. The infection was successfully treated with voriconazole.</p>

<p><strong>PURPOSE OF REVIEW: </strong>In recent years there has been an evolution of a better understanding of the pharmacology and clinical indications of existing antifungal agents and also the development of new broad-spectrum triazoles and a newer class of antifungal agents, the echinocandins. The availability of these agents has broadened the therapeutic options of invasive fungal disease among children and consequently antifungal therapy has become increasingly complex.</p>

<p><strong>RECENT FINDINGS: </strong>Adoption of adult guidelines' recommendations has been used to guide pediatric treatment as specific pediatric data were often lacking. This approach has not always selected the most appropriate therapy for newborns or young infants, as the under-dosage of voriconazole based on adult data revealed. Therefore, a detailed understanding of the available antifungal agents in children is crucial for the successful treatment of these serious infections.</p>

<p><strong>SUMMARY: </strong>In this review we summarize the main findings regarding antifungal treatment among children that have been recently published, focusing on the pharmacology and pediatric use of newer antifungal agents.</p>