Contrasting methods to operationalize antibiotic exposure in clinical research: a real-world application on healthcare-associated Clostridioides difficile infection.

The goal of this article is to summarize common methods of antibiotic operationalization used in clinical research and demonstrate methods for exposure variable selection. We demonstrate three methods for modeling exposure, using data from a case-control study on Clostridioides difficile infection in hospitalized patients: 1) factor analysis, 2) logistic regression models, and 3) Least Absolute Shrinkage and Selection Operator (LASSO) regression. The factor analysis identified 8 variables contributing the most variation in the dataset: any antibiotic exposure; number of antibiotic classes; number of antibiotic courses; dose; and specific classes monobactam, 𝛽-lactam 𝛽-lactamase inhibitors, rifamycin, and cephalosporin. The logistic regression models resulting in the best model fit used predictors representing any antibiotic exposure and the proportion of a patient's hospitalization on antibiotics. The LASSO model selected 22 variables for inclusion in the predictive model, of which 10 were antibiotic exposure variables, including: any antibiotic exposure; classes 𝛽-lactam 𝛽-lactamase inhibitors, carbapenem, cephalosporin, fluoroquinolone, monobactam, rifamycin, sulfonamides, and miscellaneous; and proportion of hospitalization on antibiotics. Investigators studying antibiotic use should consider multiple characteristics of exposure informed by their research question and the theory on how antibiotics may impact the distribution of the outcome in their target population.

Exposure to Gastric Acid-Suppression Therapy Is Associated With Health Care- and Community-Associated Clostridium difficile Infection in Children.

OBJECTIVE: The aim of the study was to determine whether gastric acid-suppression therapy is associated with Clostridium difficile infection (CDI) in both inpatient and outpatient pediatric populations. METHODS: We conducted a retrospective case-control study at a 200-bed academic pediatric hospital and associated outpatient clinics during 2005-2010. We defined cases as children 1 to 18 years of age with a first positive test for C difficile toxin A/B, and matched each case to 2 controls without C difficile. We conducted chart review to elicit selected comorbidities and exposure to gastric acid-suppression therapy and antibiotics in the preceding 3 months of the infection or encounter date. We used bivariate and multivariable logistic regression to evaluate the association between antacid use and CDI, controlling for potential confounders. RESULTS: We identified 138 children with health care- or community-associated CDIs and 276 controls. The use of any acid suppression therapy was more common in cases compared with controls (34% vs 20%, P = 0.002). When adjusted for demographic variables and comorbidities, gastric acid-suppression therapy remained significantly associated with CDI (adjusted odds ratio [aOR] 1.8, 95% confidence interval [CI] 1.0-3.1). Antibiotic use (aOR 1.7, 95% CI 1.1-2.7) and immunosuppressed state were also associated with CDI in our adjusted model (aOR 2.5, 95% CI 1.2-5.2). CONCLUSIONS: Gastric acid-suppression therapy was associated with both health care- and community-associated CDIs in children. Larger pediatric studies are necessary to determine the role of proton pump inhibitors specifically in causing CDI in children.

Clinical Practice Guideline by the Pediatric Infectious Diseases Society (PIDS) and the Infectious Diseases Society of America (IDSA): 2023 Guideline on Diagnosis and Management of Acute Bacterial Arthritis in Pediatrics.

This clinical practice guideline for the diagnosis and treatment of acute bacterial arthritis (ABA) in children was developed by a multidisciplinary panel representing the Pediatric Infectious Diseases Society (PIDS) and the Infectious Diseases Society of America (IDSA). This guideline is intended for use by healthcare professionals who care for children with ABA, including specialists in pediatric infectious diseases and orthopedics. The panel's recommendations for the diagnosis and treatment of ABA are based upon evidence derived from topic-specific systematic literature reviews. Summarized below are the recommendations for the diagnosis and treatment of ABA in children. The panel followed a systematic process used in the development of other IDSA and PIDS clinical practice guidelines, which included a standardized methodology for rating the certainty of the evidence and strength of recommendation using the GRADE approach (Grading of Recommendations Assessment, Development and Evaluation) (see Figure 1). A detailed description of background, methods, evidence summary and rationale that support each recommendation, and knowledge gaps can be found online in the full text.

Meningococcal Vaccination:: An Update on Meningococcal Vaccine Recommendations for the Primary Care Physician.

Neisseria meningitidis is an aerobic, gram-negative, diplococcus bacterium that is a leading cause of meningitis and sepsis in the United States. Particularly at-risk groups include those with complement deficiencies, people using complement inhibitors, individuals with anatomic or functional asplenia, patients with HIV infection and travelers to endemic countries. There are currently three quadrivalent meningococcal vaccines (Serogroups A, C, W, Y) and two recombinant serogroup B vaccines available for use in the United States, and recommendations for vaccine use have changed rapidly in the past 10-15 years. This article summarizes updated ACIP recommendations for meningococcal vaccination for the primary care provider.

Clinical Practice Guideline by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America: 2021 Guideline on Diagnosis and Management of Acute Hematogenous Osteomyelitis in Pediatrics.

This clinical practice guideline for the diagnosis and treatment of acute hematogenous osteomyelitis (AHO) in children was developed by a multidisciplinary panel representing Pediatric Infectious Diseases Society (PIDS) and the Infectious Diseases Society of America (IDSA). This guideline is intended for use by healthcare professionals who care for children with AHO, including specialists in pediatric infectious diseases, orthopedics, emergency care physicians, hospitalists, and any clinicians and healthcare providers caring for these patients. The panel's recommendations for the diagnosis and treatment of AHO are based upon evidence derived from topic-specific systematic literature reviews. Summarized below are the recommendations for the diagnosis and treatment of AHO in children. The panel followed a systematic process used in the development of other IDSA and PIDS clinical practice guidelines, which included a standardized methodology for rating the certainty of the evidence and strength of recommendation using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. A detailed description of background, methods, evidence summary and rationale that support each recommendation, and knowledge gaps can be found online in the full text.

Antimicrobial prescription errors in hospitalized children: role of antimicrobial stewardship program in detection and intervention.

BACKGROUND: Antimicrobial stewardship programs (ASP) are an effective strategy to ensure that antibiotics are used in accordance with scientific evidence to improve patient outcome, minimize antimicrobial (AM) resistance, and reduce hospital costs. The article describes the impact of the implementation of an ASP on AM prescription errors. METHODS: Prospective, single-center study performed at a tertiary pediatric teaching hospital that actively monitored 13 targeted AMs (amikacin, amphotericin B, cefepime, ceftriaxone, ciprofloxacin, fluconazole, levofloxacin, linezolid, meropenem, piperacillin-tazobactam, tobramycin, vancomycin, and voriconazole) and microbiology data. The ASP was implemented using CareNet and PharmNet. An infectious disease physician and pharmacist determined the need for intervention. RESULTS: The authors screened 5564 dispensed prescriptions of the 13 targeted AMs. The rate of AM errors associated with these was 0.09/1000 doses administered and 5 errors/1000 patient days. CONCLUSIONS: Active surveillance and optimization of computerized physician order entry system allows early detection and intervention of AMs prescriptions errors in hospitalized children.

Hepatitis C in Pregnant Women and Their Children.

Hepatitis C virus (HCV) infection presents unique challenges in the setting of pregnancy. HCV can contribute to pregnancy-related morbidity and pregnancy can influence the course of HCV infection. There is a significant risk of transmission to the fetus and newborn infant. Identification of HCV infection in women of childbearing potential and those who are currently pregnant offers important opportunities for the woman and for past, present and future children.

Modeling HPV vaccination scale-up among urban young men who have sex with men in the context of HIV.

INTRODUCTION: Young men who have sex with men (YMSM) are at high risk to contract human papillomavirus (HPV). While an effective vaccination exists, its use among YMSM is markedly lower compared to non-MSM and women. This study compares scaling up HPV vaccination in conjunction with other prevention strategies. METHODS: An agent-based model of urban YMSM (≤26 years of age) reflective of the demography of Philadelphia, PA, simulated for up to ten years of follow-up to examine anal and oral transmission of the HPV genotypes covered in the nonavalent (9v) vaccine: 6, 11, 16, 18, 31, 33, 45, 52, 58. Starting HPV prevalences ranged from a high of 18% (type 6) to a low of 6% (type 31); overall 65% of individuals carried any HPV genotype. Simulated levels of vaccination were ranged from 0% to 13% (present-day level), 25%, 50%, 80% (Healthy People 2020 target), and 100% in conjunction with condom use and HIV seroadaptive practices. The primary outcome was the relative reduction in HPV infection. RESULTS: Compared to present-day vaccination levels (13%), scaling-up vaccination led to expected declines in 10-year post-simulation HPV prevalence. Anal HPV (any 9v types) declined by 9%, 27%, 46%, and 58% at vaccination levels of 25%, 50%, 80%, and 100%, respectively. Similarly, oral HPV (any 9v types) declined by 11%, 33%, 57%, and 71% across the same levels of vaccine uptake. Comparing the prevention strategies, condoms blocked the greatest number of anal transmissions when vaccination was at or below present-day levels. For oral transmission, vaccination was superior to condom use at all levels of coverage. CONCLUSIONS: Public health HPV preventions strategies should continue to emphasize the complementary roles of condoms and vaccination, especially for preventing oral infection. Improving vaccination coverage will ultimately have the greatest impact on reducing HPV infection among YMSM.

Why are young infants tested for herpes simplex virus?

BACKGROUND: The polymerase chain reaction (PCR)-based test to detect herpes simplex virus (HSV) genome in cerebrospinal fluid (CSF) has become the test of choice for diagnosing this infection. The utility of this test in young infants undergoing sepsis evaluations is unknown. OBJECTIVES: We sought to identify the factors that prompted physicians to include HSV PCR in their evaluation of young infants undergoing lumbar puncture. In addition, the impact of ordering this test on patient management was assessed. METHODS: This case-control study included infants 0 to 60 days who were evaluated by lumbar puncture at the Alfred I. duPont Hospital for Children over a 5-year period. Case patients had CSF HSV PCR ordered as part of their evaluation and control patients did not. RESULTS: Eighty-eight case patients and 83 control patients were identified. The median patient age was 12 days and most patients (55%) were male. Both groups were similar in demographics. Herpes simplex virus infection was diagnosed by PCR in 3.4% of cases. The occurrence of a seizure (adjusted odds ratio [OR], 8.3; 95% confidence interval [CI], 1.7-41.0), the performance of CSF enteroviral PCR testing (adjusted OR, 4.7; 95% CI, 1.4-15.8), and the decision to obtain hepatic transaminases (adjusted OR, 5.6; 95% CI, 2.7-11.8) were associated with the decision to perform CSF HSV PCR testing. Use of health care resources associated with PCR testing was considerable. DISCUSSION: The occurrence of a seizure, the performance of CSF enteroviral PCR testing, and the decision to obtain hepatic transaminases were independently associated with the decision to perform CSF HSV PCR testing. Features traditionally associated with neonatal HSV infection, such as elevated numbers of CSF white blood cells or red blood cells, did not appear to influence the decision to perform CSF HSV PCR testing. The yield of testing in this population was low. Clinicians should weigh the benefits of early diagnosis in a few patients against the consequences of excessive testing in this population.

Spatial and environmental correlates of organism colonization and infection in the neonatal intensive care unit.

OBJECTIVE: To examine organism colonization and infection in the neonatal intensive care unit as a result of environmental and spatial factors. STUDY DESIGN: A retrospective cohort of infants admitted between 2006 and 2015 (n = 11 428), to assess the relationship between location and four outcomes: methicillin-resistant Staphylococcus aureus (MRSA) colonization; culture-confirmed late-onset sepsis; and, if intubated, endotracheal tube colonization with Pseudomonas aeruginosa or Klebsiella pneumonia. Independent risk factors were identified with mixed-effects logistic regression models and Moran's I for spatial autocorrelation. RESULT: All four outcomes statistically clustered by location; neighboring colonization also influenced risk of MRSA (p < 0.05). For P. aeruginosa, being in a location with space for more medical equipment was associated with 2.61 times the odds of colonization (95% CrI: 1.19, 5.78). CONCLUSION: Extrinsic factors partially explained risk for neonatal colonization and infection. For P. aeruginosa, infection prevention efforts at locations with space for more equipment may lower future colonization.

Safety and efficacy of enfuvirtide for 48 weeks as part of an optimized antiretroviral regimen in pediatric human immunodeficiency virus 1-infected patients.

BACKGROUND: Enfuvirtide is the only entry inhibitor approved for the treatment of human immunodeficiency virus (HIV)-1 infection. It is approved for use in adults and dosage recommendations exist for children aged 6 years or older. METHODS: T20-310 was a multicenter, open-label, nonrandomized, noncomparative study of the safety and efficacy of 2.0 mg/kg (maximum 90 mg) twice-daily subcutaneous enfuvirtide for 48 weeks in 52 treatment-experienced, HIV-1-infected pediatric patients (3-16 years) receiving optimized background therapy. RESULTS: Enfuvirtide was generally well tolerated, and no new patterns of adverse events compared with adults were observed. Mild-to-moderate injection-site reactions were the most common adverse event. Of those participants on treatment for 48 weeks, the median change from baseline in HIV-1 RNA was -1.17 log10 copies/mL (n = 32), and there was a median CD4 change of +106 (n = 25) cells/mm3 and +4.7 CD4%. Seventeen (32.7%) patients achieved a viral load decrease of > or =1 log10 copies/mL and 11 (21.2%) achieved HIV-1 RNA <400 copies/mL. Virologic and immunologic treatment responses were substantially better for children (<11 years) than adolescents. Steady-state mean enfuvirtide C(trough) levels were stable during 24 weeks with no differences between children and adolescents. CONCLUSIONS: Enfuvirtide is an effective treatment for HIV-1 infection in children and adolescents receiving optimized background therapy and has a favorable safety profile. Efficacy in adolescents was inferior; probably related to unique adherence challenges. The long-term safety and efficacy of enfuvirtide in pediatric patients is comparable to that observed in adults.

Increased incidence of head and neck abscesses in children.

OBJECTIVE: To describe increasing incidence and changing microbiology of head and neck abscesses in children admitted to the hospital during the first quarters of 2000 through 2003. STUDY DESIGN AND SETTING: Retrospective data warehouse review identified 89 children less than 19 years of age admitted to a tertiary care pediatric hospital during the first quarters of 2000 through 2003 for suspicion of head and neck abscess involving the neck, face, and peritonsillar, retropharyngeal, and parapharyngeal spaces; and for orbital and intracranial complications of acute sinusitis. OUTCOME MEASURES: Outcome measures included the incidence of infection admissions and description of infection location and microbiology, calculated by chi2 technique. RESULTS: The incidence of infections increased in 2003. The greatest increase was in neck abscesses and complications of acute sinusitis. CONCLUSIONS: The increase in group A strep infections may be related to its biologic properties. SIGNIFICANCE: Group A strep remains a significant cause of head and neck infections in children.

Assessing Occupancy and Its Relation to Healthcare-Associated Infections.

Occupancy has been associated with risk for healthcare-associated infections, yet its definition varies widely. Occupancy can be modeled as a function of census, acuity of the patient care unit, staffing ratio, or some combination. This article discusses the appropriate parameterization of these measures and how to interpret their impact. Infect Control Hosp Epidemiol 2016:1-3.

A Network Model of Hand Hygiene: How Good Is Good Enough to Stop the Spread of MRSA?

BACKGROUND Simulation models have been used to investigate the impact of hand hygiene on methicillin-resistant Staphylococcus aureus (MRSA) transmission within the healthcare setting, but they have been limited by their ability to accurately model complex patient-provider interactions. METHODS Using a network-based modeling approach, we created a simulated neonatal intensive care unit (NICU) representing the potential for per-hour infant-infant MRSA transmission via the healthcare worker resulting in subsequent colonization. The starting prevalence of MRSA colonized infants varied from 2% to 8%. Hand hygiene ranged from 0% (none) to 100% (theoretical maximum), with an expected effectiveness of 88% inferred from literature. RESULTS Based on empiric care provided within a 1-hour period, the mean number of infant-infant MRSA transmissible opportunities per hour was 1.3. Compared to no hand hygiene and averaged across all initial colonization states, colonization was reduced by approximately 29%, 51%, 67%, 80%, and 86% for the respective levels of hygiene: 24%, 48%, 68%, 88%, and 100%. Preterm infants had a 61% increase in MRSA colonization, and mechanically ventilated infants had a 27% increase. CONCLUSIONS Even under optimal hygiene conditions, horizontal transmission of MRSA is possible. Additional prevention paradigms should focus on the most acute patients because they are at greatest risk. Infect Control Hosp Epidemiol 2017;38:945-952.

Pediatricians knowledge, views, and perspectives on smallpox and smallpox vaccine.

Increasing concerns regarding smallpox as a biologic weapon have led to massive production of vaccinia vaccine and targeted vaccination campaigns. A regional mail survey was conducted among pediatricians to assess their knowledge and perceptions on smallpox and smallpox vaccine. Fifty-nine percent of the responders were unable to differentiate chickenpox from smallpox, and the majority would not accept vaccination in the absence of an outbreak and would not recommend smallpox vaccine to their patients. Even in previously vaccinated pediatricians, willingness to receive smallpox vaccine is poor and vaccination campaigns in the absence of a smallpox outbreak may not be successful.

Diagnostic utility of Borrelia burgdorferi cerebrospinal fluid polymerase chain reaction in children with Lyme meningitis.

BACKGROUND: Cerebrospinal fluid (CSF) laboratory tests are frequently collected to help differentiate Lyme meningitis from other causes of aseptic meningitis. Previous studies using Lyme CSF polymerase chain reaction (PCR) have yielded varied results (sensitivity between 10 and 90%). No studies have specifically examined the diagnostic utility of Lyme CSF-PCR in North American children with Lyme meningitis. METHODS: Retrospective chart review of children presenting to a children's hospital in a Lyme-endemic region between October 1999 and September 2004. Patients were included if they had both Lyme serology and Lyme CSF-PCR performed during the same hospital encounter and had documented meningitis. Patients were considered to have Lyme meningitis if they had meningitis and met CDC criteria for Lyme disease. The Lyme CSF-PCR assay amplified a Borrelia burgdorferi DNA flagellin gene sequence. RESULTS: Of 108 patients with meningitis who qualified for the study, 20 patients met criteria for Lyme meningitis and 88 were classified as aseptic meningitis. Positive Lyme CSF-PCR was found in 1 patient (1 of 20, 5%) with Lyme meningitis and one patient classified as aseptic meningitis (1 of 88, 1%). Lyme CSF-PCR had a sensitivity of 5% and a specificity of 99%. The only Lyme meningitis patient with positive Lyme CSF-PCR had the highest CSF white blood cell count and CSF protein values compared with the other Lyme meningitis patients. CONCLUSIONS: This is the first study to evaluate Lyme CSF-PCR exclusively in North American children. This commercially available laboratory test is not generally helpful for identifying Lyme meningitis because of its low sensitivity.

Musculoskeletal infections in children.

Serious musculoskeletal infections in children include osteomyelitis, septic arthritis, pyomyositis, and necrotizing fasciitis. The epidemiology, pathophysiology, and microbiology of each of these infections are reviewed. Specific diagnostic studies and management strategies are discussed. Prompt recognition and treatment is emphasized to prevent potential long-term sequelae.

Diagnosis, treatment, and prevention of Lyme disease in children.

The approaches to diagnosing and treating Lyme disease (LD) have been improved and refined as a result of basic and clinical research, and considerable practical experience. In addition, there have been recent studies that have allowed improvements in the ability to prevent infection with Borrelia burgdorferi. This paper will review the relevant literature and address recent developments in the diagnosis, treatment, and prevention of LD. Issues specifically related to the management of children will be identified. Controversies regarding treatment approaches will be examined in some detail. Understanding the clinical manifestations, or stage, of LD is crucial when approaching both diagnosis and treatment. Early localized disease is best diagnosed by recognizing the characteristic skin lesion, erythema migrans. Early disease will frequently, but not always, be accompanied by a detectable antibody response, particularly IgM antibody to the spirochete. Late disease, chiefly arthritis, is generally associated with high levels of IgG antibody. Western blot technology allows confirmation of enzyme immunoassay results and is especially useful when the latter is in the low or equivocal range. Early localized disease responds well to oral antibacterial therapy. Early disseminated disease, often associated with neurologic findings, may require parenteral therapy. The arthritis associated with LD frequently responds to oral antibacterials, but some refractory cases may require intravenous therapy, and occasionally surgery. Doxycycline is the oral antibacterial of choice, while amoxicillin and cefuroxime axetil are alternatives that may be preferred in young children. Owing to its long half-life and once daily dose administration, intravenous ceftriaxone has become the accepted standard for parenteral therapy. Tick avoidance has long been the mainstay for preventing LD. Antibacterial prophylaxis, using doxycycline, for tick bites has been shown to be an effective approach to prevention, but its relevance to pediatrics is uncertain. Vaccines designed to prevent infection have also been developed.