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Background: Antimicrobial resistance (AMR) is a global health problem requiring a reduction in inappropriate antibiotic prescribing. Point-of-Care C-Reactive Protein (POCCRP) tests could distinguish between bacterial and non-bacterial causes of fever in malaria-negative patients and thus reduce inappropriate antibiotic prescribing. However, the cost-effectiveness of POCCRP testing is unclear in low-income settings., Methods: A decision tree model was used to estimate cost-effectiveness of POCCRP versus current clinical practice at primary healthcare facilities in Afghanistan. Data were analysed from healthcare delivery and societal perspectives. Costs were reported in 2019 USD. Effectiveness was measured as correctly treated febrile malaria-negative patient. Cost, effectiveness and diagnostic accuracy parameters were obtained from primary data from a cost-effectiveness study on malaria rapid diagnostic tests in Afghanistan and supplemented with POCCRP-specific data sourced from the literature. Incremental cost-effectiveness ratios (ICERs) reported the additional cost per additional correctly treated febrile malaria-negative patient over a 28-day time horizon. Univariate and probabilistic sensitivity analyses examined the impact of uncertainty of parameter inputs. Scenario analysis included economic cost of AMR per antibiotic prescription., Results: The model predicts that POCCRP intervention would result in 137 fewer antibiotic prescriptions (6%) with a 12% reduction (279 prescriptions) in inappropriate prescriptions compared to current clinical practice. ICERs were $14.33 (healthcare delivery), $11.40 (societal), and $9.78 (scenario analysis) per additional correctly treated case., Conclusions: POCCRP tests could improve antibiotic prescribing among malaria-negative patients in Afghanistan. Cost-effectiveness depends in part on willingness to pay for reductions in inappropriate antibiotic prescribing that will only have modest impact on immediate clinical outcomes but may have long-term benefits in reducing overuse of antibiotics. A reduction in the overuse of antibiotics is needed and POCCRP tests may add to other interventions in achieving this aim. Assessment of willingness to pay among policy makers and donors and undertaking operational trials will help determine cost-effectiveness and assist decision making., Competing Interests: The commercial affiliation of two authors (SD and TL) does not alter our adherence to PLOS ONE policies on sharing data and materials

Background: Data on piperacillin-tazobactam pharmacokinetics and optimal dosing in children with cancer and fever are limited. Our objective was to investigate piperacillin pharmacokinetics and the probability of target attainment (PTA) with standard intermittent administration (IA), and to simulate PTA in other dosing regimens., Procedure: This prospective pharmacokinetic study was conducted from April 2016 to January 2018. Children with cancer receiving empiric piperacillin-tazobactam to treat infections were included. Piperacillin-tazobactam 100 mg/kg was infused over 5 min every 8 hours (IA). An optimized sample schedule provided six blood samples per subject for piperacillin concentration determination. The evaluated targets included: (1) 100% time of free piperacillin concentration above the minimum inhibitory concentration (fT > MIC) and (2) 50% fT > 4× MIC. MIC 50 and MIC 90 were defined based on an intrainstitutional MIC range., Results: A total of 482 piperacillin concentrations were obtained from 43 children (aged 1-18 years) during 89 fever episodes. Standard IA resulted in insufficient target attainment, with significant differences in piperacillin pharmacokinetics for different body weights. Median fT > MIC was 61.2%, 53.5%, and 36.3% for MIC 50 (2.0 mg/L), MIC 90 (4.0 mg/L), and breakpoint for Pseudomonas aeruginosa (16.0 mg/L), respectively. Correspondingly, the median fT > 4× MIC was 43%, 36.3%, and 20.1%. Simulations showed that only continuous infusion reached a PTA of 95% for MIC = 16.0 mg/L, while extended infusion lasting half of the dosing interval reached a PTA of 95% for MIC ≤ 8 mg/L., Conclusions: Our data revealed insufficient PTA with standard IA of piperacillin-tazobactam in children with cancer and fever. Alternative dosing strategies, preferably continuous infusion, are required to ensure adequate PTA., (© 2019 Wiley Periodicals, Inc.)

To date, very few studies have addressed nonneutropenic fever (NNF) in children with cancer, and there are no consensus guidelines. This scoping review aims to describe the rate of bacteremia, risk factors for infection and management, and outcomes of NNF in this population. Across 15 studies (n = 4106 episodes), the pooled-average bacteremia rate was 8.2%, and risk factors included tunneled external central venous catheter, clinical instability, and higher temperature. In two studies, antibiotics were successfully withheld in a subset of low-risk patients. Overall outcomes of NNF appear favorable; however, further research is required to determine its true clinical and economic impact., (© 2019 Wiley Periodicals, Inc.)

Thyroid abscess is a very rare clinical condition. It usually occurs in immunocompromised individuals or those with underlying malignancy. We report a case of multiple thyroid abscesses in the patient with Pre B acute lymphoblastic leukaemia which developed secondary to hematogenous spread from pyomyositis of right calf muscle. The patient developed sepsis-associated disseminated intravascular coagulation, which got resolved after thyroidectomy. He became afebrile after surgical intervention. Unfortunately, all the cultures were negative. Since there are few case series and reports, there are no clear guidelines for management of thyroid abscess. We conclude that though rare, thyroid abscess may be the cause of persistent fever in immunocompromised patients., Competing Interests: Conflicts of Interest: None declared., (2016 BMJ Publishing Group Ltd.)

Introduction: Papillon-Lefèvre Syndrome is a rare autosomal recessive disorder characterized by diffuse, transgradient palmoplantar keratoderma, destructive periodontitis beginning in childhood, premature loss of primary teeth, and frequent cutaneous and systemic pyogenic infections. Pyogenic liver abscess is an uncommon presentation of the disease present in this case., Case Presentation: A 16-year-old Punjabi, Pakistani boy presented to the outpatient department of a tertiary-care hospital of Lahore with high-grade fever of 2 months duration. He had been treated for a pyogenic liver abscess 2 years back with antibiotics followed by incision and drainage. He had poor orodental hygiene, palmoplantar keratoderma and periodontitis. His parents had history of consanguinity. His brother and two cousins had similar skin lesions and were edentulous. An orthopentogram showed atrophy of the alveolar bone. He was treated with broad-spectrum antibiotics, and antipyretics for systemic infection. Multivitamins, topical steroids, topical keratolytics and emollients were used for his dermatological issues., Conclusions: Our patient was successfully treated. His fever settled and his skin lesions improved with antibiotics, topical steroids and keratolytics. He was sent home and was asked to return for follow-up on a monthly basis.

Kikuchi-Fujimoto disease (KFD) is an unusual cause of lymphadenopathy and fever. Pregnancy associated with KFD presents as a diagnostic dilemma for clinicians. The diagnosis can be confirmed with invasive biopsies or non-invasive gene analysis. We report a case of a 24-year-old woman at 18 weeks' gestation with a neck lump and histologically confirmed KFD., (2015 BMJ Publishing Group Ltd.)

Background: The Lab-score, based on the combined determination of procalcitonin, C-reactive protein and urinary dipstick results, has been shown accurate in detecting serious bacterial infections (SBI) in children with fever without source (FWS) on retrospective cohorts. We aimed to prospectively assess the utility of the Lab-score in safely decreasing antibiotic prescriptions in children with FWS and to determine its diagnostic characteristics compared to common SBI biomarkers., Methods: Randomized controlled trial in children 7 days to 36 months old with FWS, allocated either to the Lab-score group (Lab-score reported, blinded WBC count) or to the control group (WBC, bands and C-reactive protein determined, blinded procalcitonin and Lab-score), followed up until recovery. Demographic data, antibiotic prescription rate, admission rate and diagnostic properties of the Lab-score were analyzed., Results: 271 children were analyzed. No statistically significant difference concerning antibiotic prescription rate was observed: 41.2% (54 of 131) in the Lab-score group and 42.1% (59 of 140) in the control group (p = 1.000). If recommendations based on the Lab-score had been strictly applied, a hypothetical 30.6% treatment rate would have been encountered, compared to the overall 41.7% observed rate (p = 0.0095). A Lab-score ≥3 showed the following characteristics: sensitivity 85.1% (95% CI: 76.5-93.6%), specificity 87.3% (95% CI: 82.7-91.8%), positive predictive value 68.7% (95% CI: 58.7-78.7%), negative predictive value 94.1% (95% CI: 91.5-97.9%), positive and negative likelihood ratios: 6.68 and 0.17 respectively. Area under the receiver operating characteristic curve was best for the Lab-score (0.911, 95% CI: 0.871-0.950)., Discussion: No difference regarding antibiotic treatment rate was observed when using the Lab-score, due to lack of adherence to the related recommendations. However, if strictly followed, a significant 26.5% reduction of antibiotic prescriptions would have been encountered. Medical education needs to be reinforced in order to observe rather than treat low-risk well-appearing children with FWS., Trial Registration: ClinicalTrials.gov NCT02179398.

Objective: To study the clinical characteristics, antibiotics sensitivity and outcome of group B streptococcus (GBS) meningitis in neonates in order to provide the guide for early diagnosis and appropriate treatment., Method: A retrospective review was performed and a total of 13 cases of neonatal purulent meningitis caused by GBS were identified in the Neonatal Intensive Care Unit of Yuying Children's Hospital of Wenzhou Medical University from January 1, 2005 to May 31, 2013. The clinical characteristics, antibiotics sensitivity test results and outcome were analyzed., Result: Fever, poor feeding, seizure and lethargy were common clinical signs of neonatal purulent meningitis caused by GBS. Three cases of early onset GBS meningitis received prepartum antibiotics. All 13 cases had abnormal C-reactive protein (CRP) level, and 11 cases had increased CRP within hours after admission. Of the 13 patients, 7 were cured, 4 discharged with improvement, 2 patients died during hospitalization after being given up because of serious complication. The average length of stay for recovered patients was (47 ± 21)d. Acute complications mainly included hyponatremia (5 cases), intracranial hemorrhage (3 cases) , ventriculomegaly (3 cases) , subdural collection (2 cases) , hydrocephalus (2 cases), septic shock (2 cases), cerebral hernia (1 case), encephalomalacia (1 case). One preterm patient with early onset GBS meningitis died 1 month after hospital discharge. Among 7 survivors with 10-24 months follow-up, 3 were early onset GBS meningitis, 2 with normal results of neurologic examination, 1 with delayed motor development, 4 were late onset GBS meningitis, 1 with normal results of neurologic examination, 3 were neurologically impaired with manifestations including delayed motor development (2 cases) and seizures (1 case). All the GBS strains were sensitive to penicillin and linezolid (13/13, 10/10), the susceptibility to levofloxacin, ampicillin and vancomycin were 11/12, 9/10, 8/13 respectively., Conclusion: The clinical manifestations of neonatal purulent meningitis caused by GBS are usually non-specific. It is associated with long hospitalization, neurological impairments and sequelae. Monitoring of serum CRP level is valuable for early diagnosis. Antepartum prophylaxis, early diagnosis and therapy are vital. Large dose penicillin is the priority choice to treat the neonatal purulent meningitis caused by GBS, linezolid should be used in intractable cases.

Objective: To analyze clinical manifestations, treatment and prognosis of 4 cases with endemic typhus., Method: The clinical data of four endemic typhus patients in prognosis were retrospectively analyzed. These four atypical cases of endemic typhus with pneumonia were treated in our department from October 2011 to March 2012. They were all male, with an age range of 15 months to 7 years. The four patients had long history, mild respiratory symptom and no improvement was found after treatment with cephalosporins. There were no evidences of bacterial, viral, or fungal infections and we thought they might have infection with other pathogen. Three were from rural areas. Routine blood tests, Weil-Felix reaction, blood smear (Giemsa staining) , and indirect immunofluorescence assay were performed., Result: Blood smear and IFA tests showed evidences for endemic typhus. The clinical presentations were atypical, the patients had no headache, but all had fever, rash, and pneumonia of varying severity. None of the patients had a severe cough, but bronchial casts were observed in one case. Recurrent fever was reported in three cases. Physical examinations showed no eschars, but one patient had a subconjunctival hemorrhage, and one had skin scratches, cervical lymphadenopathy, pleural effusion, pericardial effusion, and cardiac dilatation. Two patients had remarkably increased peripheral blood leukocyte counts; both these patients also had high alanine aminotransferase (ALT) levels and one had a high C-reactive protein (CRP) level. Weil-Felix testing was negative or the OX19 titer was low. The peripheral blood smear (Giemsa stain) showed intracellular pathogens in all four cases. After combined therapy with doxycycline and macrolide antibiotics, all four patients recovered well., Conclusion: The endemic typhus children often come from rural areas. The clinical presentations were atypical, they usually have no headache, but have fever (often Periodic fever) , rash, and pneumonia of varying severity in these four cases. Combined therapy with doxycycline and macrolide antibiotics was effective in all four patients.

Background and Purpose: The objective of this study was to document the clinical experience of cefpirome use in the treatment of febrile neutropenia in everyday medical practice., Methods: This was an open, non-controlled multicenter study. Patients with fever and neutropenia were started on cefpirome empirically. Response to therapy was evaluated 72 to 96 h after the beginning of treatment. The primary endpoint, clinical response, was classified as: improvement (disappearance of fever and the other signs and symptoms of infection) or failure (the patient died during the therapy or had no response to the antibiotic regimen; i.e., fever persisted and the patient's clinical condition was not improving, requiring a change in antibiotic therapy). The secondary endpoints were time to the resolution of fever and improvement of neutropenia, and microbiological response evaluated on-treatment or post-treatment., Results: 140 patients were enrolled in this study; clinical response was analyzed on the clinically evaluated population after 72 to 96 h of treatment. Among the 69 evaluated patients, 58 patients (84.1%) were improved and 11 patients (15.9%) failed. Overall, among the enrolled 140 patients, 124 patients' clinical outcomes were improved after treatment and 16 patients failed. The mean time to fever resolution was 3.1 days. Mean temperature reduced from a baseline reading of 38.7 degrees C to 37.2 degrees C (p<0.0001). Moreover, the mean neutrophil count (342.7/mm(3) at baseline) increased significantly to 3664/mm(3) (p<0.0001) after 72 to 96 h of treatment. Twenty five pathogens were isolated from 20 patients (13 Gram-positive and 9 Gram-negative). The eradication rate was 72% on-treatment or post-treatment, and the mean time to eradication was 5 days., Conclusions: Cefpirome improves clinical signs and symptoms of infection and offers improved coverage against some Gram-positive and Gram-negative pathogens in patients with febrile neutropenia. Thus, cefpirome is likely to be a valuable and cost-effective extended-spectrum agent for the empiric treatment of severe infections.

We evaluated the timing and pattern of changes in the complete blood cell count that preceded marrow recovery during 107 consecutive episodes of fever and neutropenia in 64 children with cancer. Four measures derived from serial daily measurement of the complete blood cell count were evaluated: total leukocyte count, absolute neutrophil count, absolute phagocyte count, and platelet count. During 70 (65%) of these 107 episodes, patients were discharged with an absolute neutrophil count of fewer than 500 cells/mm3; 24 patients were discharged from the hospital despite an absolute neutrophil count of fewer than 100 cells/mm3. During all but one of these 70 episodes, however, signs of early marrow recovery were present before discharge; sustained increases were observed in these patients' leukocyte, absolute neutrophil, absolute phagocyte, and platelet counts 2 or more days before their discharge in 41%, 49%, 50%, and 39% of cases, respectively. Although they were neutropenic at discharge, most patients had signs of multilineage marrow recovery at that time; 59 of 70 had increases in three of four of the measurements that we studied. None of the 69 patients who had evidence of marrow recovery at discharge had recurrence of fever. We conclude that children with cancer who were hospitalized for fever during periods of neutropenia have increases in the peripheral blood cell count that herald imminent bone marrow recovery, often several days before the absolute neutrophil count recovers to 500 cells/mm3. Our success in discharging such patients before resolution of neutropenia suggests that further controlled trials are needed to evaluate the safety and feasibility of cessation of antibiotic therapy and early discharge from the hospital.