Surgery-Associated Infections among Infants Born Extremely Preterm.

OBJECTIVE: To assess the burden of invasive infection following surgery (surgery-associated infections [SAI]) among infants born extremely premature. STUDY DESIGN: This was an observational, prospective study of infants born at gestational age 22-28 weeks hospitalized for >3 days, between April 1, 2011, to March 31, 2015, in academic centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. SAI was defined by culture-confirmed bacteremia, fungemia, or meningitis ≤14 days following a surgical procedure. RESULTS: Of 6573 infants, 1154 (18%) who underwent surgery were of lower gestational age (mean [SD]: 25.5 [1.6] vs 26.2 [1.6], P < .001), lower birth weight (803 [220] vs 886 [244], P < .001), and more likely to have a major birth defect (10% vs 3%, P < .001); 64% had 1 surgery (range 1-10 per infant). Most underwent gastrointestinal procedures (873, 76%) followed by central nervous system procedures (150, 13%). Eighty-five (7%) infants had 90 SAIs (78 bacteremia, 5 fungemia, 1 bacteremia and meningitis, 6 meningitis alone). Coagulase-negative staphylococci were isolated in 36 (40%) SAI and were isolated with another organism in 5 episodes. Risk of SAI or death ≤14 days after surgery was greater after gastrointestinal compared with central nervous system procedures (16% vs 7%, adjusted relative risk [95% CI]: 1.95 [1.15-3.29], P = .01). Death ≤14 days after surgery occurred in 141 of the 1154 infants; 128 deaths occurred after gastrointestinal surgeries. CONCLUSIONS: Surgical procedures were associated with bacteremia, fungemia, or meningitis in 7% of infants. The epidemiology of invasive postoperative infections as described in this report may inform the selection of empiric antimicrobial therapy and postoperative preventive care.

Common Behaviors and Faults When Doffing Personal Protective Equipment for Patients With Serious Communicable Diseases.

BACKGROUND: The safe removal of personal protective equipment (PPE) can limit transmission of serious communicable diseases, but this process poses challenges to healthcare workers (HCWs). METHODS: We observed 41 HCWs across 4 Ebola treatment centers in Georgia doffing PPE for simulated patients with serious communicable diseases. Using human factors methodologies, we obtained the details, sequences, and durations of doffing steps; identified the ways each step can fail (failure modes [FMs]); quantified the riskiness of FMs; and characterized the workload of doffing steps. RESULTS: Eight doffing steps were common to all hospitals-removal of boot covers, gloves (outer and inner pairs), the outermost garment, the powered air purifying respirator (PAPR) hood, and the PAPR helmet assembly; repeated hand hygiene (eg, with hand sanitizer); and a final handwashing with soap and water. Across hospitals, we identified 256 FMs during the common doffing steps, 61 of which comprised 19 common FMs. Most of these common FMs were above average in their riskiness at each hospital. At all hospitals, hand hygiene, removal of the outermost garment, and removal of boot covers were above average in their overall riskiness. Measurements of workload revealed that doffing steps were often mentally demanding, and this facet of workload correlated most strongly with the effortfulness of a doffing step. CONCLUSIONS: We systematically identified common points of concern in protocols for doffing high-level PPE. Addressing FMs related to hand hygiene and the removal of the outermost garment, boot covers, and PAPR hood could improve HCW safety when doffing high-level PPE.We identified ways that doffing protocols for high-level personal protective equipment may fail to protect healthcare workers. Hand hygiene, removing the outermost garment, boot covers, and respirator hood harbored the greatest risk and failed in similar ways across different hospitals.

Variability in the Duration and Thoroughness of Hand Hygiene.

We observed 354 hand hygiene instances across 41 healthcare workers doffing personal protective equipment at 4 hospital-based biocontainment units. We measured the duration and thoroughness of each hand hygiene instance. Both parameters varied substantially, with systematic differences between hospitals and differences between healthcare workers accounting for much of the variance.

Design Strategies for Biocontainment Units to Reduce Risk During Doffing of High-level Personal Protective Equipment.

BACKGROUND: Few data exist to guide the physical design of biocontainment units, particularly the doffing area. This can impact the contamination risk of healthcare workers (HCWs) during doffing of personal protective equipment (PPE). METHODS: In phase I of our study, we analyzed simulations of a standard patient care task with 56 trained HCWs focusing on doffing of high-level PPE. In phase II, using a rapid cycle improvement approach, we tested different balance aids and redesigned doffing area layouts with 38 students. In phase III, we tested 1 redesigned layout with an additional 10 trained HCWs. We assessed the effectiveness of design changes on improving the HCW performance (measured by occurrence and number of risky behaviors) and reducing the physical and cognitive load by comparing the results from phase I and phase III. RESULTS: The physical load was highest when participants were removing their shoe covers without any balance aid; the use of a chair required the lowest physical effort, followed by horizontal and vertical grab bars. In the revised design (phase III), the overall performance of participants improved. There was a significant decrease in the number of HCW risky behaviors (P = .004); 5 risky behaviors were eliminated and 2 others increased. There was a significant decrease in physical load when removing disposable shoe covers (P = .04), and participants reported a similar workload in the redesigned doffing layout (P = .43). CONCLUSIONS: Through optimizing the design and layout of the doffing space, we reduced risky behaviors of HCWs during doffing of high-level PPE.

Does probiotic consumption reduce antibiotic utilization for common acute infections? A systematic review and meta-analysis.

BACKGROUND: Overall reduction of antibiotic use is a widely adopted public health goal. Given evidence that consuming probiotics reduce the incidence, duration and/or severity of certain types of common acute infections, we hypothesized that probiotics are associated with reduced antibiotic use. This systematic review of randomized controlled trials (RCTs) assessed the impact of probiotic supplementation (any strain, dose or duration), compared to placebo, on antibiotic utilization for common, acute infections in otherwise healthy people of all ages. METHODS: We searched 13 electronic databases including MEDLINE, Embase and CENTRAL from inception to 17th January 2017. Backward and forward citation searches were also conducted. Two reviewers independently selected studies for inclusion and extracted study data. We assessed risk of bias for individual studies using criteria adapted from the Centre for Reviews and Dissemination, and the quality of evidence for each outcome was assessed using the GRADE system. Studies that evaluated similar outcomes were pooled statistically in meta-analyses using a random-effects model. RESULTS: We screened 1533 citations, and of these, 17 RCTs met our predefined inclusion criteria. All 17 were conducted in infants and/or children with a primary aim of preventing acute respiratory tract infections, acute lower digestive tract infections or acute otitis media. Included studies used 13 probiotic formulations, all comprising single or combination Lactobacillus and Bifidobacterium delivered in a range of food or supplement products. Mean duration of probiotic supplementation ranged from 4 days to 9 months. Trial quality was variable. Meta-analysis demonstrated that infants and children who received probiotics to prevent acute illnesses had a lower risk of being prescribed antibiotics, relative to those who received placebo (Pooled Relative Risk = 0.71, 95% CI: 0.54-0.94). When restricted to five studies with a low risk of bias, the pooled relative risk was 0.46 (95% CI: 0.23-0.97). Significant statistical heterogeneity was present in effect size estimates, which appeared to be due to one trial which could partly be considered as an outlier. CONCLUSIONS: Probiotics, provided to reduce the risk for common acute infections, may be associated with reduced antibiotic use in infants and children. Additional well-designed studies are needed to substantiate these findings in children and explore similar findings in other population groups.

Neonatal sepsis.

Neonatal sepsis is the cause of substantial morbidity and mortality. Precise estimates of neonatal sepsis burden vary by setting. Differing estimates of disease burden have been reported from high-income countries compared with reports from low-income and middle-income countries. The clinical manifestations range from subclinical infection to severe manifestations of focal or systemic disease. The source of the pathogen might be attributed to an in-utero infection, acquisition from maternal flora, or postnatal acquisition from the hospital or community. The timing of exposure, inoculum size, immune status of the infant, and virulence of the causative agent influence the clinical expression of neonatal sepsis. Immunological immaturity of the neonate might result in an impaired response to infectious agents. This is especially evident in premature infants whose prolonged stays in hospital and need for invasive procedures place them at increased risk for hospital-acquired infections. Clinically, there is often little difference between sepsis that is caused by an identified pathogen and sepsis that is caused by an unknown pathogen. Culture-independent diagnostics, the use of sepsis prediction scores, judicious antimicrobial use, and the development of preventive measures including maternal vaccines are ongoing efforts designed to reduce the burden of neonatal sepsis.

Valganciclovir for symptomatic congenital cytomegalovirus disease.

BACKGROUND: The treatment of symptomatic congenital cytomegalovirus (CMV) disease with intravenous ganciclovir for 6 weeks has been shown to improve audiologic outcomes at 6 months, but the benefits wane over time. METHODS: We conducted a randomized, placebo-controlled trial of valganciclovir therapy in neonates with symptomatic congenital CMV disease, comparing 6 months of therapy with 6 weeks of therapy. The primary end point was the change in hearing in the better ear ("best-ear" hearing) from baseline to 6 months. Secondary end points included the change in hearing from baseline to follow-up at 12 and 24 months and neurodevelopmental outcomes, with each end point adjusted for central nervous system involvement at baseline. RESULTS: A total of 96 neonates underwent randomization, of whom 86 had follow-up data at 6 months that could be evaluated. Best-ear hearing at 6 months was similar in the 6-month group and the 6-week group (2 and 3 participants, respectively, had improvement; 36 and 37 had no change; and 5 and 3 had worsening; P=0.41). Total-ear hearing (hearing in one or both ears that could be evaluated) was more likely to be improved or to remain normal at 12 months in the 6-month group than in the 6-week group (73% vs. 57%, P=0.01). The benefit in total-ear hearing was maintained at 24 months (77% vs. 64%, P=0.04). At 24 months, the 6-month group, as compared with the 6-week group, had better neurodevelopmental scores on the Bayley Scales of Infant and Toddler Development, third edition, on the language-composite component (P=0.004) and on the receptive-communication scale (P=0.003). Grade 3 or 4 neutropenia occurred in 19% of the participants during the first 6 weeks. During the next 4.5 months of the study, grade 3 or 4 neutropenia occurred in 21% of the participants in the 6-month group and in 27% of those in the 6-week group (P=0.64). CONCLUSIONS: Treating symptomatic congenital CMV disease with valganciclovir for 6 months, as compared with 6 weeks, did not improve hearing in the short term but appeared to improve hearing and developmental outcomes modestly in the longer term. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT00466817.).

Routine Supplementation of Lactobacillus rhamnosus GG and Risk of Necrotizing Enterocolitis in Very Low Birth Weight Infants.

OBJECTIVE: To evaluate if routine supplementation of Lactobacillus rhamnosus GG ATCC 53103 (LGG) is associated with a decreased risk of necrotizing enterocolitis in very low birth weight (VLBW) infants. STUDY DESIGN: Retrospective observational cohort study of VLBW (<1500 g) infants at a single center from 2008 to 2016. LGG supplementation with Culturelle at a dose of 2.5 to 5 × 109 CFU/day began in 2014. We used multivariable logistic regression to evaluate the association between LGG supplementation and necrotizing enterocolitis (modified Bell stage IIA or greater), after adjusting for potential confounders. We also compared changes in necrotizing enterocolitis incidence before and after implementation of LGG using a statistical process control chart. RESULTS: We evaluated 640 VLBW infants with a median gestational age of 28.7 weeks (IQR 26.3-30.6); 78 (12%) developed necrotizing enterocolitis. The median age at first dose of LGG was 6 days (IQR 3-10), and duration of supplementation was 32 days (IQR 18-45). The incidence of necrotizing enterocolitis in the epoch before LGG implementation was 10.2% compared with 16.8% after implementation. In multivariable analysis, LGG supplementation was associated with a higher risk of necrotizing enterocolitis (aOR 2.10, 95 % CI 1.25-3.54, P = .005). We found no special cause variation in necrotizing enterocolitis after implementation of LGG supplementation. There were no episodes of Lactobacillus sepsis during 5558 infant days of LGG supplementation. CONCLUSIONS: In this study, routine LGG supplementation was not associated with a decreased risk of necrotizing enterocolitis. Our findings do not support the use of the most common probiotic preparation currently supplemented to VLBW infants in the US.

2017 Infectious Diseases Society of America Clinical Practice Guidelines for the Diagnosis and Management of Infectious Diarrhea.

These guidelines are intended for use by healthcare professionals who care for children and adults with suspected or confirmed infectious diarrhea. They are not intended to replace physician judgement regarding specific patients or clinical or public health situations. This document does not provide detailed recommendations on infection prevention and control aspects related to infectious diarrhea.

2017 Infectious Diseases Society of America Clinical Practice Guidelines for the Diagnosis and Management of Infectious Diarrhea.

These guidelines are intended for use by healthcare professionals who care for children and adults with suspected or confirmed infectious diarrhea. They are not intended to replace physician judgement regarding specific patients or clinical or public health situations. This document does not provide detailed recommendations on infection prevention and control aspects related to infectious diarrhea.

Molecular epidemiology of norovirus in children and the elderly in Atlanta, Georgia, United States.

Noroviruses are an important cause of gastroenteritis, which can be severe at the extremes of ages. Data documenting the endemic burden of norovirus among children and elderly adults are lacking. Stool specimens submitted for clinical testing were collected from elderly (≥ 65 years) adults and children (<18 years) with acute vomiting and/or diarrhea seeking care at several metropolitan Atlanta adult and pediatric hospitals from January 2013-June 2013. Specimens were tested for norovirus with real-time RT-PCR and sequenced if norovirus was detected. Corresponding clinical and demographic data were abstracted from retrospective chart review. Norovirus was detected in 11% (11/104) of elderly specimens and 11% (67/628) of pediatric, with GII.4 Sydney_2012 detected in 64% (7/11) of elderly norovirus-positive and 11% (8/67) of pediatric specimens, P < 0.001. In comparison to hospitalized children, hospitalized elderly with norovirus were more commonly admitted to the intensive care unit (ICU) (36% vs. 7%, P = 0.02). Norovirus in the elderly can be associated with severe illness requiring ICU admissions. The pediatric group demonstrated greater variability in genotype distribution. Ongoing surveillance of norovirus genotypes is crucial for norovirus vaccine development in understanding circulating and emerging genotypes.

Infection Prevention and Control Implications of Special Pathogens in Children.

Special pathogens are broadly defined as highly transmissible organisms capable of causing severe disease in humans. Children's hospital healthcare personnel (HCP) should be prepared to identify patients possibly infected with a special pathogen, isolate the patient to minimize transmission, and inform key infection prevention, clinical, and public health stakeholders. Effective preparedness requires resources and practice with attention to education, policies and procedures, drills and training, and supplies. Successfully preparing for special pathogens is an important measure toward keeping communities, HCP, and patients and families safe in this global age that brings pathogens from across the world to our doorstep.

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

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

Recent developments and current issues in the epidemiology, diagnosis, and management of bacterial and fungal neonatal sepsis.

Identifying neonates with sepsis is complicated by variability in clinical presentation. The incidence of early onset sepsis (EOS) resulting from invasive group B streptococcal (GBS) infections has been notably reduced by the widespread delivery of intrapartum antibiotic prophylaxis. Rates of EOS attributable to non-GBS etiologies have remained constant, and ampicillin-resistant Escherichia coli has become more prevalent. Late-onset sepsis (LOS) attributable to gram-positive organisms including coagulase-negative Staphylococci and Staphylococcus aureus is associated with increased morbidity and mortality among premature infants. Invasive candidiasis is an emerging cause of LOS, especially among infants who receive broad-spectrum antimicrobial agents. Prophylactic fluconazole administration to very low-birth-weight (VLBW) neonates during the first 6 weeks of life prevents invasive candidiasis in neonatal intensive care units (NICU) with high rates of fungal infections. Targeted fluconazole prophylaxis may be beneficial in VLBW neonates who receive care in NICUs with lower rates of invasive fungal infections. Assessment of immune function, neutrophil markers, acute phase reactants, and utilization of sepsis screening scores may contribute to the management of sepsis. Maternal decolonization, antimicrobial stewardship, early enteral feeding, and optimal infection control practices are potential practical strategies for reducing the burden of neonatal sepsis.

Distinguishing Incomplete Kawasaki and Nonsevere Multisystem Inflammatory Syndrome in Children.

OBJECTIVES: Characterizing inflammatory syndromes during the coronavirus disease 2019 pandemic was complicated by recognition of multisystem inflammatory syndrome in children (MIS-C), contemporaneous with episodes of Kawasaki disease. We hypothesized a substantial overlap between the 2 and assessed the performance of an MIS-C likelihood score in differentiating inpatients with nonsevere MIS-C from prepandemic incomplete Kawasaki disease (iKD) without coronary involvement. METHODS: A retrospective review of inpatient records was conducted; the nonsevere MIS-C cohort (March 2020-February 2021) met the 2023 definition for MIS-C; the iKD cohort (January 2018-January 2019) met the American Heart Association criteria for iKD without coronary involvement. We applied the likelihood score to both cohorts. We estimated the percent of children with iKD who could have met the clinical criteria of the MIS-C, had they presented in 2023. RESULTS: The 68 children in the nonsevere MIS-C cohort were older (8 vs 4 years, P < .001) than the 28 children in the iKD cohort. Those in the nonsevere MIS-C cohort had higher rates of thrombocytopenia (P < .001) and lymphopenia (P = .021); those in the iKD cohort had higher rates of pyuria (P < .001). Twenty-four (86%) children in the iKD cohort met the 2023 MIS-C definition. The scoring system correctly predicted 71% to 74% children with their respective clinical diagnoses. CONCLUSIONS: Though there was considerable clinical overlap, thrombocytopenia, lymphopenia, and the absence of pyuria were the most helpful parameters to distinguish children with nonsevere MIS-C from those with iKD.

Successful Medical-Surgical Management of Intracardiac Thrombosis and Pulmonary Pseudoaneurysms in an Adolescent With Hughes-Stovin Syndrome.

We present an adolescent male with a single intracardiac mass and pulmonary emboli, complicated by peripheral venous thrombosis and subsequent development of pulmonary pseudoaneurysms, leading to diagnosis of Hughes-Stovin syndrome. Remission was achieved with cyclophosphamide, corticosteroids, and pseudoaneurysm resection and maintained with infliximab and methotrexate.

Emerging issues in probiotic safety: 2023 perspectives.

Probiotics are used for both generally healthy consumers and in clinical settings. However, theoretical and proven adverse events from probiotic consumption exist. New probiotic strains and products, as well as expanding use of probiotics into vulnerable populations, warrants concise, and actionable recommendations on how to work toward their safe and effective use. The International Scientific Association for Probiotics and Prebiotics convened a meeting to discuss and produce evidence-based recommendations on potential acute and long-term risks, risks to vulnerable populations, the importance for probiotic product quality to match the needs of vulnerable populations, and the need for adverse event reporting related to probiotic use. The importance of whole genome sequencing, which enables determination of virulence, toxin, and antibiotic resistance genes, as well as clear assignment of species and strain identity, is emphasized. We present recommendations to guide the scientific and medical community on judging probiotic safety.

What is the context? Probiotics, available to healthy consumers as both dietary supplements and foods, are also used by some patient populations. The goal of this paper is to determine if any new factors have emerged that would impact current views about probiotic safety for both these populations.What is new? The authors conclude that established practices are sensibly addressing factors important to the safety of traditional probiotics used by the general population. They also make recommendations regarding emerging safety considerations. Probiotics targeted for patient populations should undergo stringent testing to meet quality standards appropriate for that population, preferably verified by an independent third party. The safety of probiotics derived from species without a history of safe use must be considered on a case-by-case basis. Research is needed to address some gaps, for example which best animal models to use for safety assessment of live microbes, the possibility of antibiotic resistance gene transfer via transformation, and potential impact of probiotic-induced changes in microbiomes, interactions with drugs, and probiotic colonization.What is the impact? Probiotics of sufficient quality for patient populations are being developed and should be used accordingly. Long-term safety assessments for probiotics should be consistent with, and not more stringent than, current regulatory requirements for biologic drugs, including fecal microbial transplants. Rigor in collecting and reporting data on adverse events is needed. The authors confirm the need for understanding the entire genetic makeup of a probiotic as a cornerstone for assessing its safety.

Intravenous Antibiotic Duration for Nontyphoidal Salmonella Bacteremia in Children.

BACKGROUND AND OBJECTIVE: The optimal duration of intravenous (IV) antibiotic therapy for children with nontyphoidal Salmonella bacteremia (NTSB) is unknown. The objective of the authors of this study is to evaluate differences in outcomes among children with NTSB who received a short (≤3 days; short-duration group [SDG]) versus long (>3 days; long-duration group [LDG]) course of IV antibiotics. METHODS: This is a retrospective study of children 3 months to 18 years old with NTSB admitted to a tertiary pediatric health care system in the southeastern United States between 2008 and 2018. RESULTS: Among 57 patients with NTSB without focal infection, 24 (42%) were in the SDG and received IV antibiotics for a median of 3.0 days and 33 (58%) were in the LDG and received IV antibiotics for a median of 5.0 days. Demographic and clinical characteristics were similar between the SDG and LDG. The median total duration of antibiotics was 11.5 days in the SDG and 13.0 in the LDG (P = .068). The median length of stay was 3.0 days in the SDG and 4.0 in the LDG (P ≤ .001). Two children in the SDG (8%) and 1 child in the LDG (3%) returned to the emergency department for care unrelated to the duration of their IV antibiotic therapy (P = .567). None of the children were readmitted for sequelae related to salmonellosis. CONCLUSIONS: The duration of IV antibiotics varied for NTSB, but the outcomes were excellent regardless of the initial IV antibiotic duration. Earlier transitions to oral antibiotics can be considered for NTSB.

Management and Outcomes of Salmonella Gastroenteritis in the Era of Rapid Molecular Testing.

BACKGROUND AND OBJECTIVES: Molecular diagnostics provide a rapid and sensitive diagnosis of gastroenteritis compared with a stool culture. In this study, we seek to describe the changes in medical management and outcomes of children with Salmonella gastroenteritis as our hospital system adopted molecular diagnostics. METHODS: This study is a retrospective chart review of children <18 years of age diagnosed with nontyphoidal Salmonella gastroenteritis between 2008 and 2018 at a large pediatric health care system in the southeastern United States. Those with immunocompromising conditions and hemoglobinopathies were excluded. Patients diagnosed via molecular testing were compared with those diagnosed solely by stool culture for aspects of management including admission rates, blood culture obtainment, and antibiotic administration. RESULTS: Of 965 eligible patients with Salmonella gastroenteritis, 264 (27%) had a stool molecular test and 701 (73%) only had a stool culture performed. Groups were similar in age and presentation. Those diagnosed by molecular methods had higher hospitalization rates (69% vs 50%, P <.001), more blood cultures obtained (54% vs 44%, P <.01), and received more antibiotics (49% vs 34%, P <.001) despite statistically similar rates of bacteremia (11% vs 19%, P = .05). CONCLUSIONS: The rapid diagnosis of Salmonella gastroenteritis by molecular methods was associated with increased hospital admission rates, blood culture obtainment, and antibiotic use. This suggests possible overmedicalization of uncomplicated Salmonella gastroenteritis, and clinicians should remain cognizant of the possibility of providing low-value care for uncomplicated disease.