Use of Maribavir for Multidrug Resistant Cytomegaloviremia in a Pediatric Oncology Patient.

Resistant and refractory cytomegalovirus (CMV) viremia can limit the provision of chemotherapy due to myelosuppression and end-organ dysfunction. Few therapies are available for children with clinically significant CMV viremia. We successfully used maribavir for a 4-year-old patient with lymphoma to complete his chemotherapy course. Resistance to maribavir did result after many months of therapy.

Neonatal Paenibacilliosis: Paenibacillus Infection as a Novel Cause of Sepsis in Term Neonates With High Risk of Sequelae in Uganda.

BACKGROUND: Paenibacillus thiaminolyticus may be an underdiagnosed cause of neonatal sepsis. METHODS: We prospectively enrolled a cohort of 800 full-term neonates presenting with a clinical diagnosis of sepsis at 2 Ugandan hospitals. Quantitative polymerase chain reaction specific to P. thiaminolyticus and to the Paenibacillus genus were performed on the blood and cerebrospinal fluid (CSF) of 631 neonates who had both specimen types available. Neonates with Paenibacillus genus or species detected in either specimen type were considered to potentially have paenibacilliosis, (37/631, 6%). We described antenatal, perinatal, and neonatal characteristics, presenting signs, and 12-month developmental outcomes for neonates with paenibacilliosis versus clinical sepsis due to other causes. RESULTS: Median age at presentation was 3 days (interquartile range 1, 7). Fever (92%), irritability (84%), and clinical signs of seizures (51%) were common. Eleven (30%) had an adverse outcome: 5 (14%) neonates died during the first year of life; 5 of 32 (16%) survivors developed postinfectious hydrocephalus (PIH) and 1 (3%) additional survivor had neurodevelopmental impairment without hydrocephalus. CONCLUSIONS: Paenibacillus species was identified in 6% of neonates with signs of sepsis who presented to 2 Ugandan referral hospitals; 70% were P. thiaminolyticus. Improved diagnostics for neonatal sepsis are urgently needed. Optimal antibiotic treatment for this infection is unknown but ampicillin and vancomycin will be ineffective in many cases. These results highlight the need to consider local pathogen prevalence and the possibility of unusual pathogens when determining antibiotic choice for neonatal sepsis.

Opportunities for Antibiotic Reduction in Pediatric Patients With Urinary Tract Infection After Discharge From the Emergency Department.

OBJECTIVES: The aim of this study was to evaluate how often antibiotics are adjusted by providers, specifically discontinued or de-escalated to a more narrow-spectrum agent, based on final culture and susceptibility results, when treating patients diagnosed with a urinary tract infection (UTI) in the pediatric emergency department (ED). METHODS: This was a retrospective study of pediatric patients younger than 18 years who were discharged home from the ED with a diagnosis of UTI between January 1, 2018, and December 31, 2019. Patients were included if a urine culture was sent as part of their UTI workup and were excluded if they had been pretreated with antibiotics before the diagnosis. Discontinuation was considered possible if the urine culture had no or insignificant bacterial growth. De-escalation was defined as changing to a more narrow-spectrum antibiotic based on susceptibility testing. RESULTS: Empiric antibiotics were prescribed in 131 of 136 UTI episodes. Cefdinir (39%) and cephalexin (36%) were most commonly prescribed, but agents and durations were inconsistent. Discontinuation occurred in only 4 of 52 possible episodes (8%), resulting in a median of 6 extra days of unnecessary antibiotics per episode. For 62 of the 78 cases (79%) with culture confirmation, the prescribed empiric antibiotic was active against the isolated pathogen. A narrower agent could have been used in 29 of 62 (47%) of these cases. However, de-escalation was never attempted. Lack of de-escalation in these episodes resulted in a median of 7 extra days of unnecessary broad-spectrum antibiotic exposure. CONCLUSIONS: Inconsistent empiric antibiotics and inaccurate diagnosis result in excess antibiotic exposures for pediatric patients diagnosed with UTI. Postdischarge antimicrobial stewardship interventions are needed to reduce unnecessary antibiotic exposure in children.

The effect of simulated marine heatwaves on green-lipped mussels, Perna canaliculus: A near-natural experimental approach.

Marine heatwaves (MHW) are projected for the foreseeable future, affecting aquaculture species, such as the New Zealand green-lipped mussel (Perna canaliculus). Thermal stress alters mussel physiology highlighting the adaptive capacity that allows survival in the face of heatwaves. Within this study, adult mussels were subjected to three different seawater temperature regimes: 1) low (sustained 18 °C), 2) medium MHW (18-24 °C, using a +1 °C per week ramp) and 3) high MHW (18-24 °C, using a +2 °C per week ramp). Sampling was performed over 11 weeks to establish the effects of temperature on P. canaliculus survival, condition, specific immune response parameters, and the haemolymph metabolome. A transient 25.5-26.5 °C exposure resulted in 61 % mortality, with surviving animals showing a metabolic adjustment within aerobic energy production, enabling the activation of molecular defence mechanisms. Utilisation of immune functions were seen within the cytology results where temperature stress affected the percentage of superoxide-positive haemocytes and haemocyte counts. From the metabolomics results an increase in antioxidant metabolites were seen in the high MHW survivors, possibly to counteract molecular damage. In the high MHW exposure group, mussels utilised anaerobic metabolism in conjunction with aerobic metabolism to produce energy, to uphold biological functions and survival. The effect of exposure time was mainly seen on very long-, and long chain fatty acids, with increases observed at weeks seven and eight. These changes were likely due to the membrane storage functions of fatty acids, with decreases at week eleven attributed to energy metabolism functions. This study supports the use of integrated analytical tools to investigate the response of marine organisms to heatwaves. Indeed, specific metabolic pathways and cellular markers are now highlighted for future investigations aimed at targeted measures. This research contributes to a larger program aimed to identify resilient mussel traits and support aquaculture management.

Histopathological changes in the greenshell mussel, Perna canaliculus, in response to chronic thermal stress.

Climate change associated temperature challenges pose a serious threat to the marine environment. Elevations in average sea surface temperatures are occurring and increasing frequency of marine heatwaves resulting in mortalities of organisms are being reported. In recent years, marine farmers have reported summer mass mortality events of the New Zealand Greenshell mussel, Perna canaliculus, during the summer months; however, the etiological agents have yet to be determined. To elucidate the role of thermal stress, adult P. canaliculus were exposed to three chronic temperature treatments: a benign control of 17 °C and stressful elevations of 21 °C and 24 °C. Eight mussels per treatment were collected each month throughout a 14-month challenge period to identify and investigate histopathological differences among P. canaliculus populations exposed to the three temperatures. Histopathology revealed several significant deleterious alterations to tissues associated with temperature and exposure time. Increasing temperature and progression of time resulted in 1) an increase in the number of focal lipofuscin-ceroid aggregations, 2) an increase in focal hemocytosis, 3) an increase in the thickness of the sub-epithelial layer of the intestinal tract and 4) a decreased energy reserve cell (glycogen) coverage in the mantle. Prolonged exposure, irrespective of temperature, impacted gametogenesis, which was effectively arrested. Furthermore, increased levels of the heat shock protein 70 kDa (HSP 70) were seen in gill and gonad from thermally challenged mussels. The occurrence of the parasite Perkinsus olseni at month 5 in the 24 °C treatment, and month 7 at 21 °C was unexpected and may have exacerbated the fore-mentioned tissue conditions. Prolonged exposure to stable thermal conditions therefore appears to impact P. canaliculus, tissues with implications for broodstock captivity. Mussels experiencing elevated, temperatures of 21 and 24 °C demonstrated more rapid pathological signs. This research provides further insight into the complex host-pathogen-environment interactions for P. canaliculus in response to prolonged elevated temperature.

Effects of seawater temperature and acute Vibriosp. challenge on the haemolymph immune and metabolic responses of adult mussels (Perna canaliculus).

The New Zealand Greenshell™ mussel (Perna canaliculus) is an endemic bivalve species with cultural importance, that is harvested recreationally and commercially. However, production is currently hampered by increasing incidences of summer mortality in farmed and wild populations. While the causative factors for these mortality events are still unknown, it is believed that increasing seawater temperatures and pathogen loads are potentially at play. To improve our understanding of these processes, challenge experiments were conducted to investigate the combined effects of increased seawater temperature and Vibrio infection on the immune and metabolic responses of adult mussels. Biomarkers that measure the physiological response of mussels to multiple-stressors can be utilised to study resilience in a changing environment, and support efforts to strengthen biosecurity management. Mussels acclimated to two temperatures (16 °C and 24 °C) were injected with either autoclaved, filtered seawater (control) or Vibriosp. DO1 (infected). Then, haemolymph was sampled 24 h post-injection and analysed to quantify haemocyte immune responses (via flow-cytometry), antioxidant capacity (measured electrochemically) and metabolic responses (via gas chromatography-mass spectrometry) to bacterial infection. Both seawater temperature and injection type significantly influenced the immune and metabolite status of mussels. A lack of interaction effects between temperature and injection type indicated that the effects of Vibrio sp. 24 h post-infection were similar between seawater temperatures. Infected mussels had a higher proportion of dead haemocytes and lower overall haemocyte counts than uninfected controls. The proportion of haemocytes showing evidence of apoptosis was higher in mussels held at 24 °C compared with those held at 16 °C. The proportion of haemocytes producing reactive oxygen species did not differ between temperatures or injection treatments. Mussels held at 24 °C exhibited elevated levels of metabolites linked to the glycolysis pathway to support energy production. The saccharopin-lysine pathway metabolites were also increased in these mussels, indicating the role of lysine metabolism. A decrease in metabolic activity (decreases in BCAAs, GABA, urea cycle metabolites, oxidative stress metabolites) was largely seen in mussels injected with Vibrio sp. Itaconate increased as seen in previous studies, suggesting that antimicrobial activity may have been activated in infected mussels. This study highlights the complex nature of immune and metabolic responses in mussels exposed to multiple stressors and gives an insight into Vibrio sp. infection mechanisms at different seawater temperatures.

Balancing essential and non-essential metal bioavailability during hatchery rearing of Greenshell mussel (Perna canaliculus) larvae.

The use of ethylenediaminetetraacetic acid (EDTA) during bivalve hatchery production is thought to improve larval yields due to the reduced exposure to toxic metals (such as Cu); however, few studies have focused on the bioavailability of metals during the rearing process. Greenshell™ mussels (Perna canaliculus) were reared for 48 h with and without EDTA (12 µM) exposure and larvae were subsequently raised to 21 days post-fertilisation with and without EDTA exposure. Survival, shell length, algal ingestion rate, swimming activity, total metal concentration in water, bioavailable metal concentrations and larval metal accumulation were monitored for the 21 day period. Larval fitness (specifically D-yields) was improved on day 2 in the EDTA treatment, whereas an overall negative effect of EDTA treatment on fitness was observed on day 10 and 21. During the first 48 h, increased survival in the EDTA treatment is believed to be due to the reduction of bioavailable Zn concentrations in the rearing seawater. No other metal (essential or non-essential) displayed a consistent trend when comparing metal bioavailability to any of the fitness parameters measured throughout the experiment. Though the measured metal bioavailability was not clearly linked to fitness, the uptake of Al, P, Cr, Fe, Co, Ni, Zn, As, Cd, and Hg by P. canaliculus was reduced during the first 48 h, suggesting that the biological regulation of these elements is just as important as the bioavailability. Overall, treatment of the rearing seawater with 12 µM EDTA is effective for improving Greenshell™ mussel larval yields by decreasing metal bioavailability during the first two days of development but has minimal benefit between day 2 and 21.

Associations of malaria, HIV, and coinfection, with anemia in pregnancy in sub-Saharan Africa: a population-based cross-sectional study.

BACKGROUND: Malaria and HIV are common infections in Africa and cause substantial morbidity and mortality in pregnant women. We aimed to assess the association of malaria with anemia in pregnant women and to explore the joint effects of malaria and HIV infection on anemia in pregnant women. METHODS: We used nationally representative, cross-sectional demographic and health surveys (DHS) that were conducted between 2012 and 2017 across 7 countries of sub-Saharan Africa (Burundi, the Democratic Republic of the Congo, Gambia, Ghana, Mali, Senegal and Togo). The outcome variables were anemia (defined as a hemoglobin concentration < 110 g/L), and hemoglobin concentration on a continuous scale, in pregnant women at the time of the interview. We used generalized linear mixed-effects models to account for the nested structure of the data. We adjusted models for individual covariates, with random effects of the primary sampling unit nested within a country. RESULTS: A total of 947 pregnant women, ages, 15-49 y, were analyzed. Prevalence of malaria only, HIV only, and malaria- HIV coinfection in pregnant women was 31% (95% CI: 28.5 to 34.5%, n = 293), 1.3% (95% CI: 0.77 to 2.4%, n = 13) and 0.52% (95% CI: 0.02 to 1.3%, n = 5) respectively. Overall prevalence of anemia was 48.3% (95% CI: 45.1 to 51.5%). The anemia prevalence in pregnant women with malaria infection only was 56.0% (95% CI: 50.1 to 61.7%); HIV infection only, 62.5% (95% CI: 25.9 to 89.8%); malaria- HIV coinfection, 60.0 (95% CI: 17.0-92.7%) and without either infection, 44.6% (95% CI: 40.7 to 48.6%). In the fully adjusted models, malaria infection was associated with 27% higher prevalence of anemia (95% CI of prevalence ratio: 1.12 to 1.45; p = 0.004), and 3.4 g/L lower hemoglobin concentration (95% CI: - 5.01 to - 1.79; p = 0.03) compared to uninfected pregnant women. The prevalence of HIV infection and malaria-HIV coinfection was too low to allow meaningful analysis of their association with anemia or hemoglobin concentration. CONCLUSION: Malaria was associated with an increased prevalence of anemia during pregnancy.

A Systematic Literature Review Approach to Estimate the Therapeutic Index of Selected Immunosuppressant Drugs After Renal Transplantation.

BACKGROUND: Drugs that exhibit close margins between therapeutic and toxic blood concentrations are considered to have a narrow therapeutic index (NTI). The Food and Drug Administration has proposed that NTI drugs should have more stringent bioequivalence standards for approval of generic formulations. However, many immunosuppressant drugs do not have a well-defined therapeutic index (TI). METHODS: We sought to determine whether safety, efficacy, and pharmacokinetic data obtained from the medical literature through a comprehensive literature search could be used to estimate the TI of cyclosporine, tacrolimus, and sirolimus. In this analysis, we considered TI ≤2 as a criterion to define a drug as having an NTI. RESULTS: Published literature indicates that cyclosporine has a TI of 2-3, which falls just short of our criteria to be classified as having an NTI. We found sirolimus and tacrolimus to have a therapeutic range of 5-12 ng/mL and of 5-20 ng/mL, respectively, but were unable to calculate the TI. CONCLUSIONS: Although the current literature does not provide a clear indication that these drugs have an NTI, the routine use of therapeutic drug monitoring in clinical practice suggests that more stringent testing of their pharmacokinetic and pharmacodynamic properties should be performed before the approval of generic formulations.

Effectiveness of Granulocyte Colony-Stimulating Factor in Hospitalized Infants with Neutropenia.

Objective The objective of this study was to determine the time to hematologic recovery and the incidence of secondary sepsis and mortality among neutropenic infants treated or not treated with granulocyte colony-stimulating factor (G-CSF). Study Design We identified all neutropenic infants discharged from 348 neonatal intensive care units from 1997 to 2012. Neutropenia was defined as an absolute neutrophil count ≤ 1,500/µL for ≥ 1 day during the first 120 days of life. Incidence of secondary sepsis and mortality and number of days required to reach an absolute neutrophil count > 1,500/µL for infants exposed to G-CSF were compared with those of unexposed infants. Results We identified 30,705 neutropenic infants, including 2,142 infants (7%) treated with G-CSF. Treated infants had a shorter adjusted time to hematologic recovery (hazard ratio: 1.36, 95% confidence interval [CI]: 1.30-1.44) and higher adjusted odds of secondary sepsis (odds ratio [OR]: 1.50, 95% CI: 1.20-1.87), death (OR: 1.33, 95% CI: 1.05-1.68), and the combined outcome of sepsis or death (OR: 1.41, 95% CI: 1.19-1.67) at day 14 compared with untreated infants. These differences persisted at day 28. Conclusion G-CSF treatment decreased the time to hematologic recovery but was associated with increased odds of secondary sepsis and mortality in neutropenic infants. G-CSF should not routinely be used for infants with neutropenia.

Fluconazole Prophylaxis for the Prevention of Candidiasis in Premature Infants: A Meta-analysis Using Patient-level Data.

BACKGROUND: Invasive candidiasis (IC) is an important cause of sepsis in premature infants and is associated with a high risk of death and neurodevelopmental impairment. Prevention of IC has become a major focus in very low birth weight infants, with fluconazole increasingly used as prophylaxis. METHODS: We identified all randomized, placebo-controlled trials evaluating fluconazole prophylaxis in premature infants conducted in the United States. We obtained patient-level data from the study investigators and performed an aggregated analysis. The occurrence of each endpoint in infants who received prophylaxis with fluconazole vs placebo was compared. Endpoints evaluated were IC or death, IC, death, Candida colonization, and fluconazole resistance among tested isolates. Safety endpoints evaluated included clinical and laboratory parameters. RESULTS: Fluconazole prophylaxis reduced the odds of IC or death, IC, and Candida colonization during the drug exposure period compared with infants given placebo: odds ratios of 0.48 (95% confidence interval [CI], .30-.78), 0.20 (95% CI, .08-.51), and 0.28 (95% CI, .18-.41), respectively. The incidence of clinical and laboratory adverse events was similar for infants who received fluconazole compared with placebo. There was no statistically significant difference in the proportion of tested isolates that were resistant to fluconazole between the fluconazole and placebo groups. CONCLUSIONS: Fluconazole prophylaxis is effective and safe in reducing IC and Candida colonization in premature infants, and has no impact on resistance.

Electronic Health Records and Pharmacokinetic Modeling to Assess the Relationship between Ampicillin Exposure and Seizure Risk in Neonates.

OBJECTIVE: To evaluate the relationship between ampicillin dosing, exposure, and seizures. STUDY DESIGN: This was a retrospective observational cohort study of electronic health record (EHR) data combined with pharmacokinetic model derived drug exposure predictions. We used the EHR from 348 Pediatrix Medical Group neonatal intensive care units from 1997 to 2012. We included all infants 24-41 weeks gestational age, 500-5400 g birth weight, first exposed to ampicillin prior to 25 days postnatal age. Using a 1-compartment pharmacokinetic model and EHR data, we simulated maximum ampicillin concentration at steady state (Cmaxss, µg/mL) and area under the concentration time curve from 0 to 24 hours (AUC24, µg*h/dL). Using multivariable logistic regression, we evaluated association between ampicillin dosing, exposure, and seizures as documented in the EHR. RESULTS: We identified 131 723 infants receiving 134 041 courses of ampicillin for 653 506 infant-days of exposure. The median daily dose was 200 mg/kg/d (25th, 75th percentile; 100, 200). Median Cmaxss and AUC24 were 256.6 µg/mL (164.3, 291.5) and 2593 µg*h/dL (1917, 3334). On multivariable analysis, dosing was not associated with seizures. However increasing Cmaxss (OR = 1.10, 95% CI 1.03, 1.17) and AUC24 (OR 1.11, 95% CI 1.05, 1.18) were associated with increased odds of seizures. CONCLUSIONS: In this cohort of hospitalized infants, higher ampicillin exposure was associated with seizures as documented in the EHR.

Thoracoscopic side-to-side esophagogastrostomy by use of linear stapler-a simplified technique facilitating a minimally invasive Ivor-Lewis operation.

PURPOSE: Minimally invasive esophagectomy (MIE) has been met with increased interest for the surgical treatment of esophageal cancer. One critical obstacle for the implementation of MIE has been the intrathoracic anastomosis. In this study, we describe a technique of thoracoscopic intrathoracic anastomosis using a linear stapler in prone position and present the short-term outcomes of this procedure. METHODS: This prospective pilot study included 46 consecutive patients with a cancer either of the gastroesophageal junction (GEJ) or the distal esophagus who underwent either total MIE or thoracoscopic-assisted esophagectomy followed by intrathoracic stapled side-to-side anastomosis. The short-term outcomes including postoperative complications were recorded and analyzed. RESULTS: This pilot study included 41 males (89 %) and 5 females (11 %) with a mean age of 65.7 years. The majority had adenocarcinoma (93 %). Before surgery, 4 patients (8.7 %) had an incomplete endoscopic submucosal resection, 5 patients (11 %) received chemotherapy alone, and 33 patients (71 %) had chemoradiotherapy. Mean operation time was 408 minutes. Postoperative complications classified as Clavien-Dindo Grade IIIa or more severe occurred in 7 patients (15 %), of whom 4 patients (8.7 %) developed anastomotic leakages without any need for intensive care. Another 2 patients (4.3 %) required intensive care due to aspiration pneumonia and acute renal failure. No in-hospital mortality was registered. Only one patient (2.2 %) with anastomotic leakage developed postoperative anastomotic stenosis requiring balloon dilatation. CONCLUSIONS: The intrathoracic stapled side-to-side anastomosis technique seems to be feasible, safe, and easy to perform, associated with a limited postsurgical complication rate and a good functional outcome.

Sustained Reduction in Bloodstream Infections in Infants at a Large Tertiary Care Neonatal Intensive Care Unit.

BACKGROUND: Bloodstream infections (BSI) cause significant morbidity and mortality among hospitalized infants. PURPOSE: Reduction of BSIs has emerged as an important patient safety goal. Implementation of central line insertion bundles, standardized line care protocols, and health care provider education programs have reduced BSI in NICUs around the country. The ability of large tertiary care centers to decrease nosocomial infections, including BSI, has been demonstrated. However, long-term BSI reductions in infants are not well documented. We sought to demonstrate that a low incidence of BSI can be maintained over time in a tertiary care NICU. RESULTS: Baseline BSI incidence for infants admitted to the NICU was 5.15 and 6.08 episodes per 1000 infant-days in 2005 and 2006, respectively. After protocol implementation, the incidence of BSI decreased to 2.14/1000 infant-days and 2.44/1000 infant-days in 2008 and 2009, respectively. Yearly incidence remained low over the next 4 years and decreased even further to 0.20 to 0.45 infections per 1000 infant-days. This represents a 92% decrease in BSI over a period of more than 5 years. IMPLICATIONS FOR PRACTICE: Implementation of a nursing-led comprehensive infection control initiative can effectively produce and maintain a reduction in the incidence of BSI in infants at a large tertiary care NICU. IMPLICATIONS FOR RESEARCH: Additional research is needed to effectively expand prevention of central line-associated BSIs to BSIs of all etiologies.

Use and Safety of Erythromycin and Metoclopramide in Hospitalized Infants.

OBJECTIVE: Prokinetic medications are used in premature infants to promote motility and decrease time to full enteral feeding. Erythromycin and metoclopramide are the most commonly used prokinetic medications in the neonatal intensive care unit (NICU), but their safety profile is not well defined. METHODS: We conducted a large retrospective cohort study using data from 348 NICUs managed by the Pediatrix Medical Group. All of the infants exposed to ≥1 dose of erythromycin, metoclopramide, or both, from a cohort of 8,87,910 infants discharged between 1997 and 2012 were included. We collected laboratory and clinical information while infants were exposed to erythromycin or metoclopramide and described the frequency of laboratory abnormalities and clinical adverse events (AEs). RESULTS: Metoclopramide use increased from 1997 to 2005 and decreased from 2005 to 2012, whereas erythromycin use remained stable. Erythromycin use was most often associated with a diagnosis of feeding problem (40%), whereas metoclopramide was most often associated with a diagnosis of gastroesophageal reflux (59%). The most common laboratory AE during exposure to erythromycin or metoclopramide was hyperkalemia (8.6/1000 infant days on erythromycin and 11.0/1000 infant days on metoclopramide). Incidence of pyloric stenosis was greater with erythromycin than with metoclopramide (10/1095, 0.9% vs 76/19,001, 0.4%; P = 0.01), but odds were not significantly increased after adjusting for covariates (odds ratio 0.52, 95% confidence interval [CI] 0.26-1.02, P = 0.06). More infants experienced an AE while treated with metoclopramide than with erythromycin (odds ratio 1.21, 95% CI 1.03-1.43). CONCLUSIONS: Metoclopramide was associated with increased risk of AEs compared with erythromycin. Studies are needed to confirm safety and effectiveness of both the drugs in infants.

Rifampin use and safety in hospitalized infants.

OBJECTIVE: This study aims to examine the use and safety of rifampin in the hospitalized infants. STUDY DESIGN: Observational study of clinical and laboratory adverse events among infants exposed to rifampin from 348 neonatal intensive care units managed by the Pediatrix Medical Group between 1997 and 2012. RESULT: Overall, 2,500 infants received 4,279 courses of rifampin; mean gestational age was 27 weeks (5th, 95th percentile; 23, 36) and mean birth weight was 1,125 g (515; 2,830). Thrombocytopenia (121/1,000 infant days) and conjugated hyperbilirubinemia (25/1,000 infant days) were the most common laboratory adverse events. The most common clinical adverse events were medical necrotizing enterocolitis (64/2,500 infants, 3%) and seizure (60/2,500 infants, 2%). CONCLUSION: The overall incidence of adverse events among infants receiving rifampin appears low; however, additional studies to further evaluate safety and dosing of rifampin in this population are needed.

Fluconazole prophylaxis for prevention of invasive candidiasis in infants.

PURPOSE OF REVIEW: Invasive candidiasis is a serious infection in hospitalized infants that results in significant mortality and morbidity. Fluconazole is approved by the US Food and Drug Administration for prophylaxis of invasive candidiasis in patients undergoing bone marrow transplantation but is not approved for use in infants. This review will describe the history of fluconazole use for prophylaxis in infants. RECENT FINDINGS: Limiting fluconazole prophylaxis to infants with risk factors, in addition to low birth weight and early gestational age, reduces the number of infants treated with fluconazole and the duration of fluconazole therapy for each infant. SUMMARY: Fluconazole prophylaxis appears to be well tolerated for use in premature infants. Reduction in the incidence of invasive candidiasis is observed even when prophylaxis is limited to infants with multiple risk factors. Centers with a low incidence of invasive candidiasis may not benefit from fluconazole prophylaxis. Significant short-term and long-term toxicity and increases in fluconazole-resistant organisms have not been observed with fluconazole use in the intensive care nursery.

Interactive effects of elevated temperature and Photobacterium swingsii infection on the survival and immune response of marine mussels (Perna canaliculus): A summer mortality scenario.

The New Zealand Greenshell™ mussel (Perna canaliculus) is an economically important aquaculture species. Prolonged increases in seawater temperature above mussel thermotolerance ranges pose a significant threat to mussel survival and health, potentially increasing susceptibility to bacterial infections. Using challenge experiments, this study examined the combined effects of increased seawater temperature and bacterial (Photobacterium swingsii) infection on animal survival, haemocyte and biochemical responses of adult mussels. Mussels maintained at three temperatures (16, 20 and 24 °C) for seven days were either not injected (control), injected with sterile marine broth (injection control) or P. swingsii (challenged with medium and high doses) and monitored daily for five days. Haemolymph and tissue samples were collected at 24, 48, 72, 96, 120 h post-challenge and analysed to quantify bacterial colonies, haemocyte responses and biochemical responses. Mussels infected with P. swingsii exhibited mortalities at 20 and 24 °C, likely due to a compromised immune system, but no mortalities were observed when temperature was the only stressor. Bacterial colony counts in haemolymph decreased over time, suggesting bacterial clearance followed by the activation of immune signalling pathways. Total haemocyte counts and viability data supports haemocyte defence functions being stimulated in the presence of high pathogen loads at 24 °C. In the gill tissue, oxidative stress responses, measured as total antioxidant capacity and malondialdehyde (MDA) levels, were higher in infected mussels (compared to the controls) after 24h and 120h post-challenge at the lowest (16 °C) and highest temperatures (24 °C), indicating the presence of oxidative stress due to temperature and pathogen stressors. Overall, this work confirms that Photobacterium swingsii is pathogenic to P. canaliculus and indicates that mussels may be more vulnerable to bacterial pathogens under conditions of elevated temperature, such as those predicted under future climate change scenarios.

Prolonged Thrombocytopenia in a Case of MIS-C in a Vaccinated Child.

Multisystem inflammatory syndrome in children (MIS-C) has been extensively described in patients following severe acute respiratory syndrome coronavirus 2 infection. There are now questions about what MIS-C may look like in vaccinated children. Multisystem inflammatory syndrome in children has many clinical and laboratory features in common with other inflammatory disorders including Kawasaki disease and toxic shock syndrome. Rheumatologic conditions can present with similar musculoskeletal complaints and elevated inflammatory markers. Laboratory markers and clinical symptoms of MIS-C usually improve once therapy is begun. We describe a child with persistent thrombocytopenia as an example of variable presentation of MIS-C in vaccinated children. This case report discusses an atypical progression of MIS-C in a vaccinated child with a known prior positive COVID-19 polymerase chain reaction (PCR) test. She presented with nonspecific abdominal pain and fever and was found to have elevated inflammatory markers, lymphopenia, and thrombocytopenia. Intravenous immunoglobulin and steroid treatment failed to induce rapid recovery in her clinical condition or thrombocytopenia. Rheumatologic, hematologic, oncologic, and infectious causes were considered and worked up due to the uncertainty of her case and persistence of pancytopenia but ultimately were ruled out with extensive testing and monitoring. It was key to include a broad differential including viral-induced bone marrow suppression, idiopathic thrombocytopenic purpura, secondary hemophagocytic lymphohistiocytosis, systemic juvenile idiopathic arthritis, and malignancy. The spectrum of MIS-C and response to treatment continues to evolve, and prior vaccination in this child's case complicated the clinical picture further. Additional evaluation of MIS-C in vaccinated cases will permit characterization of the range of MIS-C presentation and response to standard therapy.