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The Clinical Trials Transformation Initiative convened with several groups in the pediatric antibacterial drug development community with the goal of identifying challenges and recommending ways to improve current practice. Attention to 5 major areas hold the promise of making new antibiotics available for use in children as soon as possible after they are approved for use in adults.

In this retrospective multicenter series of 154 children with cerebrospinal fluid shunt infections, the median (interquartile range) duration of antibiotic therapy was 18 (14-26) days. The time to shunt replacement was 14 (10-19) days. Management appeared to potentially differ according to the targeted pathogen and site. [ABSTRACT FROM AUTHOR]

Introduction: Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), remains a significant pathogen in children. Despite evidence of decreasing prevalence, MRSA bacteremia has been closely associated with complications, including certain infections (i.e. musculoskeletal and endovascular) linked to increased treatment failures.Areas covered: This expert review summarized recent published literature on the role of treatment, dosing and administration of antibiotics used to combat serious S. aureus infections in children. The pertinent antibiotics presented were vancomycin, oxazolidinones, semi-synthetic glycopeptides, daptomycin, tigecycline, novel cephalosporins, fosfomycin and lefamulin. Vancomycin has been the most commonly used antibiotic in empiric therapy for serious MRSA infection, with new key recommendations emphasizing a different approach to dosing and therapeutic monitoring. For other antibiotics, data remain limited or clinical trials are underway.Expert opinion: MRSA remains a significant pathogen in the pediatric population. As numerous therapeutic agents are available, many agents have limited data on usage in pediatric patients. Future studies require pharmacokinetic, safety and efficacy studies in pediatric patients to ensure appropriate therapeutic treatment and outcomes. Phage therapy has been used to treat deep-seated MRSA infections and is an emerging investigational treatment option. [ABSTRACT FROM AUTHOR]

Objective  New treatments are needed for multidrug-resistant (MDR) gram-negative infections in neonates. Ceftolozane/tazobactam is a β-lactam/β-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. [ABSTRACT FROM AUTHOR]

Objective: To evaluate augmented renal clearance (ARC) using aminoglycoside clearance (CLAMINO24h) derived from pharmacokinetic (PK) modelling.Methods: A retrospective study at two paediatric hospitals of patients who received tobramycin or gentamicin from 1999 to 2016 was conducted. Compartmental PK models were constructed using the Pmetrics package, and Bayesian posteriors were used to estimate CLAMINO24h. ARC was defined as a CLAMINO24h of ≥130 mL/min/1.73 m2. Risk factors for ARC were identified using multivariate logistic regression.Results: The final population model was fitted to 275 aminoglycoside serum concentrations. Overall clearance (L/h) was=CL0×(TBW/70)0.75×AGEH/(TMH + AGEH) + CL1 (0.5/SCr), where TBW is total body weight, H is the Hill coefficient, TM is a maturation term and SCr is serum creatinine. Median CLAMINO24h in those with versus without ARC was 157.36 and 93.42 mL/min/1.73 m2, respectively (P<0.001). ARC was identified in 19.5% of 118 patients. For patients with ARC, median baseline SCr was lower than for those without ARC (0.38 versus 0.41 mg/dL, P=0.073). Risk factors for ARC included sepsis [adjusted OR (aOR) 3.77, 95% CI 1.01-14.07, P=0.048], increasing age (aOR 1.11, 95% CI 1-1.23, P=0.04) and low log-transformed SCr (aOR 0.16, 95% CI 0.05-0.52, P=0.002). Median 24 h AUC (AUC24h) was significantly lower in patients with ARC at 45.27 versus 56.95 mg·h/L, P<0.01.Conclusions: ARC was observed in one of every five patients. Sepsis, increasing age and low SCr were associated with ARC. Increased clearance was associated with an attenuation of AUC24h in this population. Future studies are needed to define optimal dosing in paediatric patients with ARC. [ABSTRACT FROM AUTHOR]

Background: In 2017, 2.5 million newborns died, mainly from prematurity, infections, and intrapartum events. Preventing these deaths requires health systems to provide routine and emergency care at birth, and quality inpatient care for small and sick newborns. Defined levels of emergency obstetric care (EmOC) and standardised measurement of “signal functions” has improved tracking of maternal care in low- and middle-income countries (LMICs). Levels of newborn care, particularly for small and sick newborns, and associated signal functions are still not consistently defined or tracked. Methods: Between November 2016-November 2017, we conducted an online survey of professionals working in maternal and newborn health. We asked respondents to categorise 18 clinical care interventions that could act as potential signal functions for small and sick newborns to 3 levels of care they thought were appropriate for health systems in LMICs to provide: “routine care at birth”, “special care” and “intensive care”. We calculated the percentage of respondents that classified each intervention at each level of care and stratified responses to look at variation by respondent characteristics. Results: Six interventions were classified to specific levels by more than 50% of respondents as “routine care at birth,” three interventions as “special care” and one as “intensive care”. Eight interventions were borderline between these care levels. Responses were more consistent for interventions with relevant WHO clinical care guidelines while more variation in respondents’ classification was observed in complex interventions that lack standards or guidelines. Respondents with experience in lower-income settings were more likely to assign a higher level of care for more complex interventions. Conclusions: Results were consistent with known challenges of scaling up inpatient care in lower-income settings and underline the importance of comprehensive guidelines and standards for inpatient care. Further work is needed to develop a shortlist of newborn signal functions aligned with emergency obstetric care levels to track universal health coverage for mothers and their newborns. [ABSTRACT FROM AUTHOR]

Abstract: The selection of the right antibiotic and right dose necessitates clinicians understand the contribution of pharmacokinetic variability stemming from age‐related physiologic maturation and the pharmacodynamics to optimize drug exposure for clinical response. The complexity of selecting the right dose arises from the multiplicity of pediatric age groups, from premature neonates to adolescents. Body size and age (which relate to organ function) must be incorporated to optimize antibiotic dosing in this vulnerable population. In the effort to optimize and individualize drug dosing regimens, clinical pharmacometrics that incorporate population‐based pharmacokinetic modeling, Bayesian estimation, and Monte Carlo simulations are utilized as a quantitative approach to understanding and predicting the pharmacology and clinical and microbiologic efficacy of antibiotics. In addition, opportunistic study designs and alternative blood sampling strategies can serve as practical approaches to ensure successful conduct of pediatric studies. This review article examines relevant literature on optimization of antibiotic pharmacotherapy in pediatric populations published within the last decade. Specific pediatric antibiotic data, including beta‐lactam antibiotics, aminoglycosides, and vancomycin, are critically evaluated. [ABSTRACT FROM AUTHOR]

Background. The impact of 13-valent pneumococcal conjugate vaccine (PCV13) on pneumococcal meningitis (PM) in US children is unknown. We compared the serotype distribution, antibiotic susceptibility, hospital course, and outcomes of children with PM 3 years before and 3 years after the introduction of PCV13. Methods. We identified patients =18 years of age with PM at 8 children's hospitals in the United States. Pneumococcal isolates were collected prospectively. Serotyping and antibiotic susceptibility were performed in a central laboratory. Clinical data were abstracted from medical records. Patients were divided into 3 subgroups: pre-PCV13 (2007-2009), transitional year (2010), and post-PCV13 (2011-2013). Categorical variables were analyzed by the ?2 test and continuous variables by the Mann--Whitney U test. Results. During the study period, 173 of 1207 episodes (14%) of invasive pneumococcal disease were identified as PM; 76 of 645 (12%) were during 2007-2009 and 69 of 394 (18%) during 2011-2013 (50% increase; P = .03). The proportion of PCV13 serotype cases decreased from 54% in 2007-2009 to 27% in 2011-2013 (P = .001). Non-PCV13 serotype cases represented 73% of the isolates in 2011-2013. Isolates with ceftriaxone minimum inhibitory concentration =1 µg/mL decreased (13% to 3%) from 2007-2009 to 2011-2013 (P = .03). No significant differences were identified for hospital course or outcome, with the exception that a greater proportion of patients had subdural empyema and hemiparesis in 2011-2013. Conclusions. After the introduction of PCV13, the number of cases of PM in children remained unchanged compared with 2007-2009, although the proportion of PCV13 serotypes decreased significantly. Serotype 19A continued to be the most common serotype in 2011-2013. Antibiotic resistance decreased significantly. Morbidity and case-fatality rate due to PM remain substantial. [ABSTRACT FROM AUTHOR]

Infections caused by antibiotic-resistant bacteria, especially the “ESKAPE” pathogens, continue to increase in frequency and cause significant morbidity and mortality. New antimicrobial agents are greatly needed to treat infections caused by gram-negative bacilli (GNB) resistant to currently available agents. The Infectious Diseases Society of America (IDSA) continues to propose legislative, regulatory, and funding solutions to this continuing crisis. The current report updates the status of development and approval of systemic antibiotics in the United States as of early 2013. Only 2 new antibiotics have been approved since IDSA's 2009 pipeline status report, and the number of new antibiotics annually approved for marketing in the United States continues to decline. We identified 7 drugs in clinical development for treatment of infections caused by resistant GNB. None of these agents was included in our 2009 list of antibacterial compounds in phase 2 or later development, but unfortunately none addresses the entire spectrum of clinically relevant GNB resistance. Our survey demonstrates some progress in development of new antibacterial drugs that target infections caused by resistant GNB, but progress remains alarmingly elusive. IDSA stresses our conviction that the antibiotic pipeline problem can be solved by the collaboration of global leaders to develop creative incentives that will stimulate new antibacterial research and development. Our aim is the creation of a sustainable global antibacterial drug research and development enterprise with the power in the short term to develop 10 new, safe, and efficacious systemically administered antibiotics by 2020 as called for in IDSA's “10 × '20 Initiative.” [ABSTRACT FROM AUTHOR]

Background. The United States Food and Drug Administration requires clinical trial noninferiority margins to preserve a fraction (eg, 50%) of the established comparator drug's efficacy versus placebo. Lack of placebocontrolled trials for many infections complicates noninferiority margin justification for and, hence, regulatory review of new antimicrobial agents. Noninferiority margin clarification is critical to enable new antimicrobial development. In the absence of placebo-controlled trials, we sought to define the magnitude of efficacy of antimicrobial agents and resulting noninferiority margins for studies of complicated skin and skin-structure infection (SSSI). Methods. We systematically reviewed literature on complicated SSSI published during 1900-1950 (before widespread penicillin resistance) to define treatment outcomes and confidence intervals (CIs). Antimicrobial efficacy was calculated as the lower limit CI of the cure rate with antimicrobials minus the upper limit CI of the cure rate without antimicrobials. Results. We identified 90 articles describing 128,000 patients with complicated SSSI. For cellulitis/erysipelas, cure rates were 66% (95% CI, 64%-68%) without antibiotics and 98% (95% CI, 96%-99%) for penicillin-treated patients, and penicillin reduced mortality by 10%. Cure rates for wound/ulcer infections were 36% (95% CI, 32%- 39%) without antibiotics and 83% (95% CI, 81%-85%) for penicillin-treated patients. For major abscesses, cure rates were 76% (95% CI, 71%-80%) without antibiotics and 96% (95% CI, 94%-98%) for penicillin-treated patients; penicillin reduced mortality by 6%. Conclusion. Systematic review of historical literature enables rational noninferiority margin justification in the absence of placebo-controlled trials and may facilitate regulatory review of noninferiority trials. Noninferiority margins of 14% for cellulitis/erysipelas, 21% for wound/ulcer infections, and 7% for major abscesses would preserve ⩾50% of antibiotic efficacy versus placebo for these complicated SSSI subsets. [ABSTRACT FROM AUTHOR]

There are few placebo-controlled, randomized, prospective clinical trials of antibiotic therapy for community- acquired pneumonia (CAP) in children. The reduction in mortality seen in early trials of antibacterials for treatment of bacterial CAP in adults and children was dramatic and led to the adoption of antibacterial therapy as the standard of care for CAP in both adults and children. Because of the efficacy of antibacterials for treatment of CAP in adults and the reluctance of society to place children at risk of adverse outcomes in placebo-controlled clinical trials, pediatric investigations of this type were not performed after 1940. Instead, comparative trials were subsequently conducted and reported. More recently, comparative trials using a non- inferiority trial design have been used by regulatory agencies to grant approval of antibiotic therapy for pediatric CAP. We cannot reliably distinguish between pneumonia cases caused by bacterial, viral, or atypical pathogens among the relatively homogeneous population of children with CAP who are enrolled into clinical trials. Patient- or parent-reported outcomes represent an option for appropriate, defined clinical trial outcomes for pediatric CAP, because the disease in children has a relatively short and potentially self-resolving clinical course. Clinical trials that require invasive techniques for diagnosis and placebo-controlled randomized trials are not acceptable for children, who are considered to be a vulnerable population. [ABSTRACT FROM AUTHOR]

The ongoing explosion of antibiotic-resistant infections continues to plague global and US health care. Meanwhile, an equally alarming decline has occurred in the research and development of new antibiotics to deal with the threat. In response to this microbial "perfect storm," in 2001, the federal Interagency Task Force on Antimicrobial Resistance released the "Action Plan to Combat Antimicrobial Resistance; Part 1: Domestic" to strengthen the response in the United States. The Infectious Diseases Society of America (IDSA) followed in 2004 with its own report, "Bad Bugs, No Drugs: As Antibiotic Discovery Stagnates, A Public Health Crisis Brews," which proposed incentives to reinvigorate pharmaceutical investment in antibiotic research and development. The IDSA's subsequent lobbying efforts led to the introduction of promising legislation in the 109th US Congress (January 2005-December 2006). Unfortunately, the legislation was not enacted. During the 110th Congress, the IDSA has continued to work with congressional leaders on promising legislation to address antibiotic-resistant infection. Nevertheless, despite intensive public relations and lobbying efforts, it remains unclear whether sufficiently robust legislation will be enacted. In the meantime, microbes continue to become more resistant, the antibiotic pipeline continues to diminish, and the majority of the public remains unaware of this critical situation. The result of insufficient federal funding; insufficient surveillance, prevention, and control; insufficient research and development activities; misguided regulation of antibiotics in agriculture and, in particular, for food animals; and insufficient overall coordination of US (and international) efforts could mean a literal return to the preantibiotic era for many types of infections. If we are to address the antimicrobial resistance crisis, a concerted, grassroots effort led by the medical community will be required. [ABSTRACT FROM AUTHOR]

Objective: This report is limited to patients with a single cerebrospinal fluid (CSF) shunt infected by a single organism, and compares two treatment protocols. Methods: In the initial protocol (1975–1991), patients underwent removal of the shunt system and received intravenous and intraventricular antibiotics. Intraventricular antibiotics were administered twice daily to those with external ventricular drainage. When CSF was cultured 48 h off all antibiotics and found to be sterile at 24 h of incubation, a new shunt was inserted. Follow-up CSF cultures were obtained in all patients between 1–6 months following placement of the new shunt. Results: There were 25 patients (ages 1 month to 16 years; mean ± SD: 23 ± 4.0 months). CSF obtained from the shunt yielded the following: Staphylococcus epidermidis (19), Staphylococcus aureus (2), Streptococcus species (2), Serratia marcescens (1), and Propionebacterium species (1). The duration of intravenous antibiotics was 7–12 days (mean ± SD: 9.7 ± 1.3 days), and intraventricular antibiotic therapy was 6.2 ± 1.7 days. Total hospital stay was 15.2 ± 2.3 days. The follow-up period was 7.7 ± 3.6 years. Following the initial protocol in another 15 patients (1992–2004), the treatment regime was modified in that intraventricular antibiotics were administered once daily in patients with external ventricular drainage, and the CSF was cultured at 24 h off antibiotics, instead of 48 h. Results were similar to the initial protocol with respect to days of antibiotic therapy and hospital stay. Conclusion: Based on our retrospective nonrandomized series, we believe patients with a single shunt and noncompartmentalized hydrocephalus can be successfully treated without a prolonged antibiotic course and lengthy hospital stay. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Short-course antibiotic therapy for specific pediatric infections allows the clinician to minimize toxicities related to antibiotic exposure, to limit antibiotic resistance, and to improve compliance and cost without compromising microbiologic efficacy. Future studies of short-course therapy in children should address the pharmacokinetics of antibiotic exposure to the pathogen at the site of infection, the pharmacodynamics of pathogen eradication, and the many host factors involved in clinical and microbiologic outcomes. By using a mathematic model that integrates all important variables, one may be able to predict the probability of a cure with short-course therapy for each pathogen, antibiotic, site of infection, and host interaction. [ABSTRACT FROM AUTHOR]

The article presents practice guidelines for outpatient parental antomicrobial therapy. These guidelines were formulated to assist physicians and other health care professionals with various aspects of the administration of outpatient parenteral antimicrobial therapy. A thorough assessment of the patient's general medical condition, the infectious process and the home situation is necessary before starting therapy. The importance of administering the first dose of an antibiotic in a supervised setting is emphasized.

Background Pneumococcal acute otitis media (AOM) in children due to vaccine-related serotypes (ST) has declined after the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13), although some serotypes, such has 3, 19A and 19F have persisted. Among non-vaccine serotypes, 35B has been shown to contribute substantially to both OM and invasive infections. This study describes the current epidemiology of pneumococcal OM isolates obtained from the U S Pediatric Multicenter Pneumococcal Surveillance Group (USPMPSG). Methods From the USPMPSG database, we collected data from patients <18 years of age with pneumococcal OM isolates from 2014 to 2018. Analysis included demographics, immunization status, antimicrobial susceptibility data and serotype. Statistical comparisons included Fisher's exact and Wilcoxon rank-sum tests. Results A total of 494 patients with isolates were identified within the time period from 5 children's hospitals. Median age was 1.7 years (range 0–17.6) and 299 (60.5%) were male; 176 (35.7%) had an underlying condition. Thirty-two patients had received no dose of either PCV7 or PCV13. Thirty-five serotypes were identified (3 isolates were non-typeable), of which 6 serotypes [35B (16.8%), 3 (9.5%), 15A (7.9%), 15B (7.9%), 23B (7.9%) and 21 (6.1%)] caused more than half of the total OM infections (figure). Ninety (18.2%) isolates were of PCV13 serotypes. Twenty-five of 476 (5.3%) isolates had a penicillin MIC>2 µg/mL. These were of serotypes 11A, 15A/C, 19A/F, 35B and NT; 10/455 (2.2%) isolates had ceftriaxone MIC>1 µg/mL and were of ST 3, 15A, 19A/F and 35B. Conclusion Most pneumococcal OM were caused by non-PCV13 serotypes. Serotype 35B remained the most common serotype among pneumococcal isolates recovered from ear drainage or middle ear cultures. The low proportion of penicillin-resistant isolates along with the increasing proportion of AOM cases being due to non-pneumococcal isolates supports the consideration to switch routine antibiotic treatment for AOM to standard dose amoxicillin-clavulanate from high dose amoxicillin in PCV13 immunized children (Pediatr Infect Dis J 2018;37:1255–1257). Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

The article reports on the appropriate treatment course for bacterial arthritis in children. It states that a heightened awareness of increasing antimicrobial resistance in pediatrics demands that a treatment course needs to both maximize efficacy and minimize antibiotic exposure to limit the development of resistance, with the potential added benefit of decreasing antibiotic-mediated clinical toxicity. It mentions that the selection of different antibiotics, dosages and surgical management was recommended.

A letter to the editor is presented in response to Calvin Kunin's letter on antibiotic development incentives.

Infections remain a leading cause of death in neonates. The sparse antibiotic development pipeline and challenges in conducting neonatal research have resulted in few effective antibiotics being adequately studied to treat multidrug-resistant (MDR) infections in neonates, despite the increasing global mortality burden caused by antimicrobial resistance. Of 40 antibiotics approved for use in adults since 2000, only four have included dosing information for neonates in their labelling. Currently, 43 adult antibiotic clinical trials are recruiting patients, compared with only six trials recruiting neonates. We review the World Health Organization (WHO) priority pathogens list relevant to neonatal sepsis and propose a WHO multiexpert stakeholder meeting to promote the development of a neonatal priority antibiotic development list. The goal is to develop international, interdisciplinary consensus for an accelerated neonatal antibiotic development programme. This programme would enable focused research on identified priority antibiotics for neonates to reduce the excess morbidity and mortality caused by MDR infections in this vulnerable population. [ABSTRACT FROM AUTHOR]

ABSTRACT. Objective. Despite the lack of evidence defining a time interval during which cerebrospinal fluid (CSF) culture yield will not be affected by previous antibiotic therapy, recent publications cite a "minimum window" of 2 to 3 hours for recovery of bacterial pathogens after parenteral antibiotic administration. We conducted a retrospective review of children with bacterial meningitis to describe the rate at which parenteral antibiotic pretreatment sterilizes CSF cultures. Methods. The medical records of pediatric patients who were discharged from a tertiary children's hospital during a 5-year period with the final diagnosis of bacterial meningitis or suspected bacterial meningitis were reviewed. The decay in yield of CSF cultures over time was evaluated in patients with lumbar punctures (LP) delayed until after initiation of parenteral antibiotics and in patients with serial LPs before and after initiation of parenteral antibiotics. Results. The pathogens that infected the 128 study patients were Streptococcus pneumoniae (49), Neisseria meningitidis (37), group B Streptococcus (21), Haemophilus influenzae (8), other organisms (11), and undetermined (3). Thirty-nine patients (30%) had first LPs after initiation of parenteral antibiotics, and 55 (43%) had serial LPs before and after initiation of parenteral antibiotics. After ≥50 mg/kg of a third-generation cephalosporin, 3 of 9 LPs in meningococcal meningitis were sterile within 1 hour, occurring as early as 15 minutes, and all were sterile by 2 hours. With pneumococcal disease, the first negative CSF culture occurred at 4.3 hours, with 5 of 7 cultures negative from 4 to 10 hours after initiation of parenteral antibiotics. Reduced susceptibility to β-lactam antibiotics occurred in 11 of 46 pneumococcal isolates. Group B streptococcal cultures were positive through the first 8 hours after parenteral antibiotics. Blood cultures were positive in 74% of cases without pretreatment and in 57% to 68%... [ABSTRACT FROM AUTHOR]

OBJECTIVE: The purpose of this study was to monitor the clinical and microbiologic features of invasive infections caused by Streptococcus pneumoniae among children before and after the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7). DESIGN: We conducted a 15-year prospective surveillance study of all invasive pneumococcal infections in children. The sample included infants and children at 8 children's hospitals in the United States with culture-proven invasive S pneumoniae infections. RESULTS: Since the implementation of routine PCV7 immunization in 2000, invasive infections have decreased yearly from 2001 through 2004, to a nadir of 151 infections; the rate then increased from 2005 through 2008. Compared with the pre-PCV7 era, a greater proportion of children with invasive pneumococcal infection had an underlying condition in the post-PCV7 period. Compared with the total number of annual admissions, the number of 19A isolates increased significantly from 2001 to 2008 (P<.00001). In 2007 and 2008, only 16 isolates (4%) were vaccine serotypes; 19A accounted for 46% (168 of 369) of the non-PCV7 serotypes. Thirty percent of the 19A isolates were multidrug resistant. Serotypes 1, 3, and 7F accounted for 22% of the non-PCV7 serotypes. Among children with invasive pneumococcal infections, the likelihood of a 19A serotype increased with the number of preceding PCV7 doses. CONCLUSIONS: Since 2005, the number of invasive pneumococcal infections in children has increased at 8 children's hospitals, primarily as a result of serotype 19A isolates, one third of which were resistant to multiple antibiotics in 2007 and 2008. Continued surveillance is necessary to detect emerging serotypes after the planned introduction of 13-valent or other pneumococcal vaccines. [ABSTRACT FROM AUTHOR]

There is no global consensus on the conduct of clinical trials in children and neonates with complicated clinical infection syndromes. No comprehensive regulatory guidance exists for the design of antibiotic clinical trials in neonates and children. We did a systematic review of antibiotic clinical trials in complicated clinical infection syndromes (including bloodstream infections and community-acquired pneumonia) in children and neonates (0-18 years) to assess whether standardised European Medicines Agency (EMA) and US Food and Drug Administration (FDA) guidance for adults was used in paediatrics, and whether paediatric clinical trials applied consistent definitions for eligibility and outcomes. We searched MEDLINE, Cochrane CENTRAL databases, and ClinicalTrials.gov between Jan 1, 2000, and Nov 18, 2015. 82 individual studies met our inclusion criteria. The published studies reported on an average of 66% of CONSORT items. Study design, inclusion and exclusion criteria, and endpoints varied substantially across included studies. The comparison between paediatric clinical trials and adult EMA and FDA guidance highlighted that regulatory definitions are only variably applicable and used at present. Absence of consensus for paediatric antibiotic clinical trials is a major barrier to harmonisation in research and translation into clinical practice. To improve comparison of therapies and strategies, international collaboration among all relevant stakeholders leading to harmonised case definitions and outcome measures is needed. [ABSTRACT FROM AUTHOR]

Comments on an article about the use of lumbar puncture in bacterial meningitis. Diagnostic use of polymerase chain reaction; Administration of antibiotics in relation to lumbar puncture; Issues concerning the timing of performing lumbar puncture.