Unique presentation of late-onset Pneumocystis pneumonia in a pediatric kidney transplant recipient.

BACKGROUND: Restrictive lung disease leading to abnormal lung function in kidney transplant recipients is commonly associated with noninfectious complications or medications used for post-transplant immunosuppression. Herein, we report an interesting case of pediatric kidney transplant recipient with weight loss and abnormal spirometry who was diagnosed to have late-onset Pneumocystis pneumonia. CASE REPORT: A 17-year-old male patient with a history of allergic rhinitis, mild persistent asthma, and deceased donor kidney transplant, performed 18 months prior, presented for routine evaluation of his asthma to the pulmonology clinic. He was clinically asymptomatic except for a weight loss of 8 kg over 6-month period prior to presentation. Patient's spirometry was suggestive of a restrictive pattern and further investigation using a high-resolution computed tomography (HRCT) of the chest showed bilateral diffuse ground-glass reticulonodular opacities with subpleural sparing suggestive of interstitial pneumonitis. A bronchoscopy with bronchoalveolar lavage revealed organisms consistent with Pneumocystis jirovecii on gomori-methenamine-silver (GMS) staining. Beta-d-glucan testing in serum revealed a level of >500 pg/mL (normal 0-59 pg/mL) further supportive of Pneumocystis jirovecii infection. Patient was treated with a 6-week course of trimethoprim-sulfamethoxazole. His weight loss and beta-d-glucan levels improved over a course of 6 months, and he continues to be on trimethoprim-sulfamethoxazole prophylaxis. CONCLUSION: Late-onset Pneumocystis jirovecii infection in kidney transplant recipients can have an atypical presentation. Treating physicians should consider PJP in the differential diagnosis of unexplained weight loss in pediatric kidney transplant recipients, especially those receiving a large cumulative burden of immunosuppression.

Infective Endocarditis at a Referral Children's Hospital During 19-Year Period: Trends and Outcomes.

BACKGROUND: We noted a recent increase in cases of infective endocarditis (IE) at our institution. The purpose of the study is to examine the incidence, risk factors, microbiology and outcome of IE in our pediatric population. METHODS: Retrospective review of IE cases during 2002-2020 at Children's Hospital of Michigan, Detroit. RESULTS: 68 patients with IE were identified. There was a 2-fold increase in incidence during the 2012-2020 (late period) compared to the 2002-2011 (early period). The most common predisposing conditions were congenital heart disease (CHD) in 39 (57.4%) and central venous catheter (CVC) in 19 (27.9%). CHD was more frequent in the late period (29/43, 67.4%) compared to early period (10/25, 40.0%) (p = 0.042). In CHD patients, palliative or corrective cardiac surgery was performed prior to IE diagnosis in 4/25 (16%) in early period and 23/43 (53.5%) in the late period (p = 0.004). S. aureus was the most common causative organism (35.3%) followed by streptococci (22.1%). Valve replacement or valvuloplasty was performed in 22.1% of patients. Complications occurred in 20 (29.4%). Mortality occurred in 7 (10.3%): 3 had CHD, 3 had CVC and underlying conditions and 1 had fulminant MRSA infection. CONCLUSION(S): The higher incidence of IE during the late period is likely due to an increase in patients with CHD who had undergone prior cardiac surgery. S. aureus was the predominant pathogen in all patients including those with CHD, followed by streptococci. IE in children continues to be associated with high rates of morbidity and mortality.

Myopericarditis after messenger RNA Coronavirus Disease 2019 Vaccination in Adolescents 12 to 18 Years of Age.

OBJECTIVES: To characterize the clinical course and outcomes of children 12-18 years of age who developed probable myopericarditis after vaccination with the Pfizer-BioNTech (BNT162b2) coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccine. STUDY DESIGN: A cross-sectional study of 25 children, aged 12-18 years, diagnosed with probable myopericarditis after COVID-19 mRNA vaccination as per the Centers for Disease Control and Prevention criteria for myopericarditis at 8 US centers between May 10, 2021, and June 20, 2021. We retrospectively collected the following data: demographics, severe acute respiratory syndrome coronavirus 2 virus detection or serologic testing, clinical manifestations, laboratory test results, imaging study results, treatment, and time to resolutions of symptoms. RESULTS: Most (88%) cases followed the second dose of vaccine, and chest pain (100%) was the most common presenting symptom. Patients came to medical attention a median of 2 days (range, <1-20 days) after receipt of Pfizer mRNA COVID-19 vaccination. All adolescents had an elevated plasma troponin concentration. Echocardiographic abnormalities were infrequent, and 92% showed normal cardiac function at presentation. However, cardiac magnetic resonance imaging, obtained in 16 patients (64%), revealed that 15 (94%) had late gadolinium enhancement consistent with myopericarditis. Most were treated with ibuprofen or an equivalent nonsteroidal anti-inflammatory drug for symptomatic relief. One patient was given a corticosteroid orally after the initial administration of ibuprofen or an nonsteroidal anti-inflammatory drug; 2 patients also received intravenous immune globulin. Symptom resolution was observed within 7 days in all patients. CONCLUSIONS: Our data suggest that symptoms owing to myopericarditis after the mRNA COVID-19 vaccination tend to be mild and transient. Approximately two-thirds of patients underwent cardiac magnetic resonance imaging, which revealed evidence of myocardial inflammation despite a lack of echocardiographic abnormalities.

Multisystem Inflammatory Syndrome in Children: Survey of Protocols for Early Hospital Evaluation and Management.

OBJECTIVE: To describe the similarities and differences in the evaluation and treatment of multisystem inflammatory syndrome in children (MIS-C) at hospitals in the US. STUDY DESIGN: We conducted a cross-sectional survey from June 16 to July 16, 2020, of US children's hospitals regarding protocols for management of patients with MIS-C. Elements included characteristics of the hospital, clinical definition of MIS-C, evaluation, treatment, and follow-up. We summarized key findings and compared results from centers in which >5 patients had been treated vs those in which ≤5 patients had been treated. RESULTS: In all, 40 centers of varying size and experience with MIS-C participated in this protocol survey. Overall, 21 of 40 centers required only 1 day of fever for MIS-C to be considered. In the evaluation of patients, there was often a tiered approach. Intravenous immunoglobulin was the most widely recommended medication to treat MIS-C (98% of centers). Corticosteroids were listed in 93% of protocols primarily for moderate or severe cases. Aspirin was commonly recommended for mild cases, whereas heparin or low molecular weight heparin were to be used primarily in severe cases. In severe cases, anakinra and vasopressors frequently were recommended; 39 of 40 centers recommended follow-up with cardiology. There were similar findings between centers in which >5 patients vs ≤5 patients had been managed. Supplemental materials containing hospital protocols are provided. CONCLUSIONS: There are many similarities yet key differences between hospital protocols for MIS-C. These findings can help healthcare providers learn from others regarding options for managing MIS-C.

SARS-CoV-2-associated multisystem inflammatory syndrome in children: clinical manifestations and the role of infliximab treatment.

This study was conducted to assess the clinical spectrum, management, and outcome of SARS-CoV-2-related multisystem inflammatory syndrome in children (MIS-C). We reviewed medical records of children with MIS-C diagnosis seen at the Children's Hospital of Michigan in Detroit between April and June 2020. Thirty-three children were identified including 22 who required critical care (group 1) and 11 with less intense inflammation (group 2). Children in group 1 were older (median 7.0 years) than those in group 2 (median 2.0 years). Abdominal pain was present in 68% of patients in group 1. Hypotension or shock was present in 17/22 patients in group 1. Thirteen (39.4%) had Kawasaki disease (KD)-like manifestations. Five developed coronary artery dilatation; All resolved on follow-up. Intravenous immunoglobulin (IVIG) was given to all patients in group 1 and 7/11 in group 2. Second-line therapy was needed in 13/22 (group 1) for persisting inflammation or myocardial dysfunction; 12 received infliximab. All patients recovered.Conclusion: MIS-C clinical manifestations may overlap with KD; however, MIS-C is likely a distinct inflammatory process characterized by reversible myocardial dysfunction and rarely coronary artery dilatation. Supportive care, IVIG, and second-line therapy with infliximab were associated with a favorable outcome. What is Known: • Multisystem inflammatory syndrome in children (MIS-C) manifestations include fever, gastrointestinal symptoms, shock, and occasional features of Kawasaki disease (KD). • Treatment includes immunomodulatory agents, most commonly IVIG and corticosteroids. What is New: • Spectrum of MIS-C varies from mild to severe inflammation and coronary artery dilatation occurred in 5/22 (23%) critically ill patients. • IVIG and infliximab therapy were associated with a favorable outcome including resolution of coronary dilatation; only 2/33 received corticosteroids.

Ceftolozane/Tazobactam in Neonates and Young Infants: The Challenges of Collecting Pharmacokinetics and Safety Data in This Vulnerable Patient Population.

OBJECTIVE: New treatments are needed for multidrug-resistant (MDR) gram-negative infections in neonates. Ceftolozane/tazobactam is a ß-lactam/ß-lactamase inhibitor combination that has broad-spectrum activity against most common gram-negative bacteria, including MDR strains. We evaluated pharmacokinetics (PK) and safety of ceftolozane/tazobactam in term and premature neonates and young infants. STUDY DESIGN: This is a subgroup analysis of a phase 1, noncomparative, open-label, multicenter study that characterized the PK, safety, and tolerability of a single intravenous (IV) dose of ceftolozane/tazobactam in pediatric patients with proven/suspected gram-negative infection or receiving perioperative prophylaxis. RESULTS: Seven patients were enrolled in Group A (birth [7 days postnatal] to < 3 months, > 32 weeks gestation) and six patients were enrolled in Group B (birth [7 days postnatal] to < 3 months, ≤ 32 weeks gestation). PK profiles in neonates and young infants were generally comparable to those of older children receiving a single IV dose of ceftolozane/tazobactam. No serious adverse events (AEs), treatment-related AEs, severe AEs, or clinically significant laboratory abnormalities were reported. CONCLUSION: Among term and premature neonates and young infants, PK was comparable to older children and ceftolozane/tazobactam was generally well tolerated. An adaptable and flexible study design is necessary for enrollment in neonatal PK trials.

Multidrug-Resistant Pseudomonas aeruginosa Infection in a Child with Cystic Fibrosis.

We describe a pediatric cystic fibrosis patient who developed a pulmonary exacerbation due to two multidrug-resistant (MDR) Pseudomonas aeruginosa isolates. In addition to these MDR organisms, the case was further complicated by ß-lactam allergy. Despite the MDR phenotype, both isolates were susceptible to an antimicrobial combination.

An Atypical Presentation of Kawasaki Disease and Potential Markers for Diagnosis.

Cervical lymphadenopathy is seldom the initial symptom of Kawasaki disease (KD), making diagnosis difficult in early node-first Kawasaki disease (NFKD). Early treatment is important to prevent cardiovascular sequelae. This report discusses a case of a 4-year-old African American female with NFKD and retropharyngeal phlegmon who was initially treated with antibiotics for cervical lymphadenitis. She later developed classic symptoms of KD, including mucositis, conjunctivitis, palmar erythema, and truncal rash. KD was then suspected and treated appropriately, with the patient experiencing rapid clinical improvement. Early misdiagnosis of NFKD is not uncommon, but certain indices, such as patient age, elevated absolute neutrophil count, or elevated liver enzymes, may be helpful in increasing clinical suspicion. NFKD and retropharyngeal phlegmon remain a rare presentation of an already known condition. The case presented here emphasizes the need for KD to be a differential diagnosis in cases of cervical lymphadenitis and retropharyngeal abscess refractory to antibiotic treatment.

Pharmacokinetics, Efficacy, and Safety of a SARS-CoV-2 Antibody Treatment in Pediatric Participants: An Open-Label Addendum of a Placebo-Controlled, Randomized Phase 2/3 Trial.

INTRODUCTION: Bamlanivimab and etesevimab (BAM + ETE) are monoclonal antibodies (mAbs) effective in reducing COVID-19-related hospitalizations and all-cause mortality in adult participants at increased risk for severe disease. We present pharmacokinetic (PK), efficacy, and safety results from pediatric participants (< 18 years of age) with COVID-19 who were treated with BAM + ETE. METHODS: In an addendum to the phase 2/3 BLAZE-1 clinical trial (NCT04427501), pediatric participants received open-label weight-based dosing (WBD, n = 94) based on exposure-matching to the authorized dose of BAM + ETE in adult participants. For efficacy and safety assessments, placebo (n = 14) and BAM + ETE (n = 20)-treated adolescent participants (> 12 to < 18 years of age) from the BLAZE-1 trial were included in the overall pediatric population (N = 128). All participants had mild to moderate COVID-19 upon enrollment and ≥ 1 risk factor for severe COVID-19. The primary objective was to characterize the PK of BAM and ETE in the WBD population. RESULTS: The median age of the participants was 11.2 years, 46.1% were female, 57.9% were Black/African American, and 19.7% were Hispanic/Latino. The area under the curve for BAM and ETE in the WBD population was similar to that previously observed in adults. There were no COVID-19-related hospitalizations or deaths. All adverse events (AE) except one were mild or moderate, with one participant reporting a serious AE. CONCLUSION: WBD in pediatric participants achieved similar drug exposures compared to adult participants that received the authorized BAM + ETE dose. The pediatric efficacy and safety data were consistent with adults receiving mAbs for COVID-19. TRIAL REGISTRATION NUMBER: NCT04427501.

COVID-19 Infection in Children: Diagnosis and Management.

Purpose of Review: Due to the rapidly changing landscape of COVID-19, the purpose of this review is to provide a concise and updated summary of pediatric COVID-19 diagnosis and management. Recent Findings: The relative proportion of pediatric cases have significantly increased following the emergence of the Omicron variant (from < 2% in the early pandemic to 25% from 1/27 to 2/3/22). While children present with milder symptoms than adults, severe disease can still occur, particularly in children with comorbidities. There is a relative paucity of pediatric data in the management of COVID-19 and the majority of recommendations remain based on adult data. Summary: Fever and cough remain the most common clinical presentations, although atypical presentations such as "COVID toes," anosmia, and croup may be present. Children are at risk for post-infectious complications such as MIS-C and long COVID. Nucleic acid amplification tests through respiratory PCR remain the mainstay of diagnosis. The mainstay of management remains supportive care and prevention through vaccination is highly recommended. In patients at increased risk of progression, interventions such as monoclonal antibody therapy, PO Paxlovid, or IV remdesivir × 3 days should be considered. In patients with severe disease, the use of remdesivir, dexamethasone, and immunomodulatory agents (tocilizumab, baricitinib) is recommended. Children can be at risk for thrombosis from COVID-19 and anticoagulation is recommended in children with markedly elevated D-dimer levels or superimposed clinical risk factors for hospital associated venous thromboembolism.

Central line-associated blood stream infection (CLABSI) due to Candida sojae in an infant with short bowel syndrome: The first human case report.

Central line associated blood stream infections (CLABSIs) in infants and children with intestinal failure due to short bowel syndrome may be caused by different organisms due to intestinal translocation and skin contamination. We report what we believe the first case of candidemia in an infant with short bowel syndrome caused by the environmental yeast Candida sojae that was initially misidentified as Candida tropicalis. We discuss its possible sources including a central venous catheter (CVC) and gut translocation and the differences between the two Candida species.

2021 Update on the Clinical Management and Diagnosis of Kawasaki Disease.

PURPOSE OF REVIEW: Provide an updated review of the clinical management and diagnosis of Kawasaki disease with inclusion of potential diagnostic difficulties with multisystem inflammatory syndrome in children (MIS-C) given the ongoing COVID-19 pandemic. RECENT FINDINGS: Adjunctive corticosteroid therapy has been shown to reduce the rate of coronary artery dilation in children at high risk for IVIG resistance in multiple Japanese clinical studies (most notably RAISE study group). Additional adjunctive therapies (etanercept, infliximab, cyclosporin) may also provide limited benefit, but data is limited to single studies and subgroups of patients with cardiac abnormalities. The efficacy of other agents (atorvastatin, doxycycline) is currently being investigated. MIS-C is a clinically distinct entity from KD with broad clinical manifestations and multiorgan involvement (cardiac, GI, hematologic, dermatologic, respiratory, renal). MIS-C with Kawasaki manifestations is more commonly seen in children < 5 years of age. SUMMARY: The 2017 American Heart Association (AHA) treatment guidelines have included changes in aspirin dosing (including both 80-100 mg/kg/day and 30-50 mg/kg/day treatment options), consideration of the use of adjuvant corticosteroid therapy in patients at high risk of IVIG resistance, and the change in steroid regimen for refractory KD to include both pulse-dose IVMP and longer course of prednisolone with an oral taper. A significant proportion of children diagnosed with MIS-C, a post-infectious syndrome of SARS-CoV-2 infection, meet criteria for Kawasaki disease. Further investigation is warranted to further delineate these conditions and optimize treatment of these conditions given the ongoing COVID-19 pandemic.

Acute Kidney Injury in Pediatric Acute SARS-CoV-2 Infection and Multisystem Inflammatory Syndrome in Children (MIS-C): Is There a Difference?

Objective: To evaluate the prevalence and factors associated with the risk of acute kidney injury (AKI) in pediatric patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and multisystem inflammatory syndrome in children (MIS-C). Study Design: We performed a retrospective chart review of 113 patients with SARS-CoV-2 infection with or without MIS-C admitted at Children's Hospital of Michigan (CHM) from March to August 2020. Patient demographic details, laboratory data, imaging studies, echocardiography reports, and treatment data were collected. Results: Of the 92 patients included in the final analysis, 22 (24%) developed AKI with 8/22 (36%) developing stage 3 AKI. The prevalence of AKI was much higher in patients with MIS-C 15/28 (54%) vs. those with acute SARS-CoV-2 infection 7/64 (11%), (p < 0.001). Overall, when compared to patients without AKI, patients with AKI were older in age (11 vs. 6.5 years, p = 0.007), African American (86 vs. 58%, p = 0.028), had MIS-C diagnosis (68 vs. 19%, p < 0.001), required ICU admission (91 vs. 20%, p < 0.001), had cardiac dysfunction (63 vs. 16%, p < 0.001), required inotropic support (59 vs. 6%, p < 0.001) and had a greater elevation in inflammatory markers. In a multivariate analysis, requirement of inotropes [Odds Ratio (OR)-22.8, p < 0.001], African American race (OR-8.8, p = 0.023) and MIS-C diagnosis (OR-5.3, p = 0.013) were the most significant predictors for AKI. All patients had recovery of kidney function, and none required kidney replacement therapy. Conclusion: Children with acute SARS-CoV-2 infection and MIS-C are at risk for AKI, with the risk being significantly greater with MIS-C. The pathogenesis of AKI in acute SARS-CoV-2 infection appears to be a combination of both renal hypo-perfusion and direct renal parenchymal damage whereas in MIS-C, the renal injury appears to be predominantly pre-renal from cardiac dysfunction and capillary leak from a hyperinflammatory state. These factors should be considered by clinicians caring for these children with a special focus on renal protective strategies to aid in recovery and prevent additional injury to this high-risk subgroup.

COVID-19 among Minority Children in Detroit, Michigan during the Early National Surge of the Pandemic.

Background. The COVID-19 pandemic has shed light on communities of racial/ethnic minority groups in the US where long-standing health issues and structural inequities are now known to have resulted in increased risk for infection, severe illness, and death from the virus. The objective of our study was to describe demographic characteristics, clinical presentations, medical interventions and outcomes of pediatric patients with COVID-19 treated at Children's Hospital of Michigan (CHM), a tertiary care center in urban Detroit, an early hotspot during the initial surge of the SARS-CoV-2 pandemic. Methods. A retrospective chart review was performed of children ≤18 years of age who had polymerase chain reaction (RT-PCR) testing via NP swab or serum IgG antibody testing for SARS-CoV-2 during March 1, 2020-June 30, 2020. Results. Seventy-eight COVID-19 infected children were identified of whom 85.8% (67/78) were from minority populations (African American, Hispanic). Hospitalization rate was 82% (64/78). About 44% (34/78) had an associated comorbidity with asthma and obesity being most common. Although all ages were affected, infants <1 year of age had the highest hospitalization rate (19/64, 30%). In all disease severity categories, dichotomized non-whites had more severe disease by percentage within race/ethnicity than Whites, and also within percent disease severity (P-value = .197). Overall, 37% of hospitalized patients required intensive care. Conclusions. Extremely high rates of COVID-19 hospitalization and requirement of ICU care were identified in our patient population. Further studies are needed to better understand the contributing factors to this health disparity in disadvantaged communities.

Pharmacokinetics and Safety of Single-dose Tedizolid Phosphate in Children 2 to <12 Years of Age.

BACKGROUND: Infections with Gram-positive bacteria, including acute bacterial skin and skin structure infections (ABSSSIs), are common in children. We describe a single-dose pharmacokinetics and safety study of tedizolid phosphate, a new oxazolidinone under investigation for the treatment of ABSSSIs in children, in hospitalized participants 2 to <12 years of age. METHODS: This open-label, multicenter, phase 1 trial (NCT02750761) enrolled hospitalized children 2 to <12 years of age receiving treatment for a confirmed/suspected Gram-positive bacterial infection. Participants were stratified by age (2 to <6 years and 6 to <12 years) to receive a single oral or intravenous dose of tedizolid phosphate. Evaluations included safety and pharmacokinetics of tedizolid phosphate and its active metabolite, tedizolid. Palatability of the oral suspension was also evaluated. RESULTS: Thirty-two participants were enrolled and received 3-6 mg/kg of study medication. For both routes of administration, tedizolid phosphate was rapidly converted to tedizolid; median time to maximum tedizolid plasma concentration was 1-2 hours after initiation of the 1-hour intravenous infusion and 2-3 hours after oral dosing. The tedizolid mean terminal half-life was 5-6 hours and 6-7 hours for the intravenous and oral administration groups, respectively. The oral tedizolid phosphate suspension demonstrated high bioavailability comparable to that of the parenteral administration. A single dose of intravenous or oral tedizolid phosphate was well tolerated; no unexpected safety findings were observed. CONCLUSIONS: Pharmacokinetic and safety observations provide the information necessary for the continued development of tedizolid phosphate for the treatment of Gram-positive infections in children, particularly ABSSSIs.

Detection of oseltamivir resistance during treatment of 2009 H1N1 influenza virus infection in immunocompromised patients: utility of cycle threshold values of qualitative real-time reverse transcriptase PCR.

Two immunocompromised patients with 2009 H1N1 influenza pneumonia had viral shedding for over 5 weeks despite therapy with oseltamivir. Declining or persistently low cycle threshold values noted on serial qualitative real-time reverse transcriptase PCR (rRT-PCR) of respiratory specimens implied increasing viral load and probable drug resistance. Oseltamivir resistance was later confirmed by pyrosequencing.

Ceftolozane/Tazobactam Treatment of Multidrug-resistant Pseudomonas aeruginosa Infections in Children.

The clinical use, safety and effectiveness of ceftolozane/tazobactam among 13 patients 3 months to 19 years of age infected with multidrug-resistant Pseudomonas aeruginosa are described. All but one patient achieved clinical cure after initial treatment. Adverse drug events attributed to treatment included transaminitis and neutropenia which occurred in 2 patients and resolved upon dose reduction.

Plasma pharmacokinetics of ceftolozane/tazobactam in pediatric patients with cystic fibrosis.

BACKGROUND: The antipseudomonal cephalosporin/ß-lactamase inhibitor combination ceftolozane/tazobactam could be a potential treatment option for cystic fibrosis (CF) pulmonary exacerbations. The pharmacokinetics (PK) of ceftolozane/tazobactam in children with CF merits further evaluation. METHODS: This is a retrospective subgroup analysis of a phase 1, noncomparative trial that characterized PK, safety, and tolerability of single intravenous doses of ceftolozane/tazobactam in pediatric patients. This analysis compares ceftolozane and tazobactam plasma PK parameters, estimated from a population PK model, between patients with and without CF enrolled in that trial. Individual attainment of PK/pharmacodynamic (PD) targets of ceftolozane and tazobactam (free ceftolozane concentration >4 µg/mL for >30% and free tazobactam concentration >1 µg/mL for 20% of the dosing interval) in patients with and without CF were evaluated. RESULTS: The study enrolled 18 patients aged greater than or equal to 2 to less than 18 years old, which included 9 with CF. Weight-normalized ceftolozane PK parameters were similar between patients with CF (clearance: 0.16 L/h/kg, half-life: 1.54 hours, volume of distribution: 0.26 L/kg) and without CF (clearance: 0.15 L/h/kg, half-life: 1.62 hours, volume of distribution: 0.26 L/kg), as were most weight-normalized tazobactam PK parameters. Weight-normalized tazobactam clearance was higher in patients with CF (0.73 L/h/kg) than patients without CF (0.42 L/h/kg). All patients achieved the prespecified PK/PD targets for ceftolozane and tazobactam. CONCLUSIONS: This retrospective analysis demonstrated generally similar weight-normalized plasma PK parameters for ceftolozane and tazobactam among children with and without CF; thus, projected doses for treatment of pediatric hospital-acquired/ventilator-associated pneumonia, which are higher than the pediatric complicated urinary tract infection/intra-abdominal infection doses, may be appropriate for treatment of CF pulmonary exacerbation.

Multidrug-resistant viridans streptococcus (MDRVS) osteomyelitis of the mandible successfully treated with moxifloxacin.

Multidrug-resistant viridans group streptococcus (MDRVS) strains have emerged as important pathogens. Treatment of MDRVS infections is problematic. The use of fluoroquinolones for treatment of MDRVS osteomyelitis has not been established. We present the first case of MDRVS osteomyelitis of the mandible successfully treated with sequential intravenous then oral moxifloxacin, and review the literature on the subject.

Traveler's diarrhea: updates for pediatricians.

Children who travel are at risk of developing the same illnesses that affect adult travelers. Treatment, etiology and actual risk of TD in children are not well defined. Prevention and self-treatment of TD should be discussed in great detail during pre-travel counseling. This includes information and instructions on various preventive measures as well as when to use medications and the potential adverse effects associated with these medications. A TD that is mild can be managed effectively by appropriate use of oral rehydration solutions. Families should be advised to carry ORS packets and start treatment in children as soon as the diarrhea begins. Self treatment with antibiotics such as azithromycin may be considered in children if diarrhea is moderate to severe. Caregivers should contact local health authorities if there is no improvement especially after self treatment with antibiotics.