Comparative Safety and Attributable Healthcare Expenditures Following Inappropriate Versus Appropriate Outpatient Antibiotic Prescriptions Among Adults With Upper Respiratory Infections.

BACKGROUND: Little is known about the clinical and financial consequences of inappropriate antibiotics. We aimed to estimate the comparative risk of adverse drug events and attributable healthcare expenditures associated with inappropriate versus appropriate antibiotic prescriptions for common respiratory infections. METHODS: We established a cohort of adults aged 18 to 64 years with an outpatient diagnosis of a bacterial (pharyngitis, sinusitis) or viral respiratory infection (influenza, viral upper respiratory infection, nonsuppurative otitis media, bronchitis) from 1 April 2016 to 30 September 2018 using Merative MarketScan Commercial Database. The exposure was an inappropriate versus appropriate oral antibiotic (ie, non-guideline-recommended vs guideline-recommended antibiotic for bacterial infections; any vs no antibiotic for viral infections). Propensity score-weighted Cox proportional hazards models were used to estimate the association between inappropriate antibiotics and adverse drug events. Two-part models were used to calculate 30-day all-cause attributable healthcare expenditures by infection type. RESULTS: Among 3 294 598 eligible adults, 43% to 56% received inappropriate antibiotics for bacterial and 7% to 66% for viral infections. Inappropriate antibiotics were associated with increased risk of several adverse drug events, including Clostridioides difficile infection and nausea/vomiting/abdominal pain (hazard ratio, 2.90; 95% confidence interval, 1.31-6.41 and hazard ratio, 1.10; 95% confidence interval, 1.03-1.18, respectively, for pharyngitis). Thirty-day attributable healthcare expenditures were higher among adults who received inappropriate antibiotics for bacterial infections ($18-$67) and variable (-$53 to $49) for viral infections. CONCLUSIONS: Inappropriate antibiotic prescriptions for respiratory infections were associated with increased risks of patient harm and higher healthcare expenditures, justifying a further call to action to implement outpatient antibiotic stewardship programs.

Prevalence of respiratory bacterial pathogens and associated management factors in dairy calves in Taiwan.

This study aimed to investigate the prevalence at both farm-level and calf-level and to identify the risk factors of respiratory bacterial pathogens in dairy calves in Taiwan. The status of bovine respiratory disease (BRD) was evaluated by using the Wisconsin scoring system from a total of 400 pre-weaned calves from 32 different farms in Taiwan, then the nasopharyngeal swabs were collected. The prevalence of respiratory pathogens was 84.37% at farm-level and 45.50% at calf-level, and Pasteurella multocida (P. multocida) was the most prevalent pathogen. The presence of Mycoplasma bovis (M. bovis), P. multocida, Mannheimia haemolytica (M. haemolytica) and Histophilus somni (H. somni) were all higher in BRD positive calves than BRD negative calves, but only in H. somni was significant (P<0.001). Then nine farm management risk factors were analyzed by using multivariate logistic regression models to determine the risk factors of respiratory bacterial pathogens (farm and calf-level). In the result at farm-level, only unheated colostrum was significantly associated with pathogen positive farms (Odds Ratio (OR)=11.43). At calf-level, the predominant risk factor for each pathogen, M. bovis, P. multocida, M. haemolytica and H. somni, was late first colostrum feeding (OR=272.82), unheated colostrum (OR=3.41), waste milk feeding (OR=6.59) and high pneumonia treatment cost (OR=2.52), respectively. For effective preventive measures, farmer education on milk and colostrum feeding are urgently warranted.

The economic impact of infection requiring hospitalization on venous leg ulcers.

OBJECTIVE: To determine the impact of infection (INF) on medical resource utilization (MRU) and cost of care in patients with venous leg ulcers (VLU). METHODS: We performed a retrospective case-control study of 78 patients followed for a minimum of 12 months with C6 VLUs treated by vascular surgeons, at our wound center. To eliminate minor episodes of INF or incorrectly diagnosed episodes, only patients who had an inpatient admission specifically for INF comprised the INF group, whereas all other admissions were excluded for this group. MRU was defined as the number of clinic visits, Visiting Nurse Association (VNA) visits, and inpatient admissions. The actual cost for treatment was determined using financial data provided by both the hospital and physician organization billing units. The total cost over the 1-year follow-up period comprised individual cost centers: inpatient and outpatient facility fees, physician fees, and visiting nurse services. Mean MRU and cost data were compared using the two-sample t-test between INF and NON-INF. RESULTS: Of the 78 patients with C6 VLU, 9 (11.5%) had at least one inpatient admission for INF related to their VLU in the 1-year treatment period, with an additional five recurrent admissions for a total of 14 admissions, whereas 69 NON-INF had three NON-INF-related admissions. There was no difference between INF and NON-INF for usual risk factors, but INF had a greater proportion of congestive heart failure (44%; 13%, P < .02). Regarding MRU, both the number of outpatient wound center visits (INF 16.89 ± 6.41; NON-INF 9.46 ± 7.7, P = .008) and VNA blocks (INF 3.89 ± 2.93; NON-INF 1.94 ± 2.24, P < .02) were greater for INF. Total costs for INF ($27,408 ± $10,859) were threefold higher than those for NON-INF ($11,088 ± $9343, P < .0001) and subsequent VNA costs were doubled for INF ($9956 ± $4657) vs NON-INF ($4657 ± $5486, P = .01). CONCLUSIONS: INFs in patients with VLU led to an overall increase in MRU and cost of care, with the INF cohort requiring more inpatient admissions, outpatient visits, and VNA services than NON-INF. Given the major impact INF has on cost and MRU, better treatment modalities that prevent INF as well as identifying risk factors for INF in patients with VLU are needed.

Epidemiology of serious bacterial infection in febrile infants under 3 months of age and diagnostic management in Mayotte.

OBJECTIVE: This study aimed to determine the prevalence of serious bacterial infections (SBIs) in infants less than 90 days old presenting with fever on arrival at the emergency department (ED), and to assess the diagnostic management of febrile infants. DESIGN: A retrospective study at Mamoudzou Hospital, Mayotte Island, French Department. SETTING: General ED in the only pediatric hospital throughout the territory PATIENTS: We included infants less than 90 days old with a history of fever and bacterial investigation evaluated in the ED between 2016 and 2018. We excluded preterm infants (gestational age < 37 weeks) and those with known immunodeficiency or previous administration of antibiotics. RESULTS: A total of 594 infants were included. In all, 105 infants (17.7%) were diagnosed with an SBI and 28 (4.7%) with an invasive bacterial infection of which 1.34% was meningitis. The most frequent SBI was pneumonia (n = 69, 11.6%) followed by urinary tract infection (UTI; n = 37, 6.2%). Predominant pathogens (excluding contaminants) were Escherichia coli (51.2% of the UTI cases), group B Streptococcus (62.5% of meningitis cases), and Staphylococcus aureus (61.5% of bacteremia cases). Seven infants presented with bacterial pneumonia due to Staphylococcus aureus with Panton-Valentine leucocidin (PVL) exotoxin production. Ill-appearing infants, clinical signs of SBI and complex chronic condition were associated with a risk of SBI (respective odds ratio [OR]: 4.6, 95% confidence interval [CI]: 3-6.9; OR: 4.2, 95% CI: 2.8-6.4; and OR: 3.2, 95% CI: 1.2-8.5). The median age for SBI was 42 days (5-90). Fever without source (FWS) occurred more often in infants under 21 days of age (48.5% vs. 31.3% in older infants, p < 0.001). The median duration of fever at home was 24 h (6-96). Concerning management, in infants aged under 21 days, there were more lumbar punctures (58.3% vs. 23% in older infants, p < 0.001) and more frequent initiation of empiric antibiotics (62.6% vs. 42.7%, p < 0.001). Length of stay was also longer in this age range (5 days vs. 3 days, p = 0.037). CONCLUSION: Delay in medical consultation in the case of fever, the risk of SBI regardless of age, and unusual epidemiology with many IBI due to Staphylococcus aureus with PVL exotoxin production are specific characteristics observed in our study. Knowledge of the current epidemiology of SBI in Mayotte would be useful for setting up a risk-stratified protocol in this population in the future.

Changes in the epidemiology and management of bacterial infections in cirrhosis.

Patients with cirrhosis are susceptible to develop infections because of immune dysfunction, changes in microbiome and increase in bacterial translocation from the gut to systemic circulation. Bacterial infections can worse the clinical course of the disease, triggering the development of complications such as acute kidney injury, hepatic encephalopathy, organ failures and acute on chronic liver failure. In recent years, the spread of multi drug resistant bacteria made more challenging the management of infections in patients with cirrhosis. Hence, the mortality rate associated to sepsis is increasing in these patients. Therefore, the optimization of the management of infections has a high priority in cirrhosis. Herein we reviewed the recent changes in the epidemiology and the management of bacterial infections in patients with liver cirrhosis.

Cost Analysis of Emergency Department Criteria for Evaluation of Febrile Infants Ages 29 to 90 Days.

OBJECTIVE: To compare the medical costs associated with risk stratification criteria used to evaluate febrile infants 29-90 days of age. STUDY DESIGN: A cost analysis study was conducted evaluating the Boston, Rochester, Philadelphia, Step-by-Step, and PECARN criteria. The percentage of infants considered low risk and rates of missed infections were obtained from published literature. Emergency department costs were estimated from the Centers for Medicare and Medicaid Services. The Health Care Cost and Utilization Project databases were used to estimate the number of infants ages 29-90 days presenting with fever annually and costs for admissions related to missed infections. A probabilistic Markov model with a Dirichlet prior was used to estimate the transition probability distributions for each outcome, and a gamma distribution was used to model costs. A Markov simulation estimated the distribution of expected annual costs per infant and total annual costs. RESULTS: For low-risk infants, the mean cost per infant for the criteria were Rochester: $1050 (IQR $1004-$1092), Philadelphia: $1416 (IQR, $1365-$1465), Boston: $1460 (IQR, $1411-$1506), Step-by-Step $942 (IQR, $899-$981), and PECARN $1004 (IQR, $956-$1050). An estimated 18 522 febrile 1- to 3-month-old infants present annually and estimated total mean costs for their care by criteria were: Rochester, $127.3 million (IQR, $126.1-$128.5); Philadelphia, $129.9 million (IQR, $128.7-$131.1); Boston, $128.7 million (IQR, $127.5-$129.9); Step-by-Step, $ 126.6 million (IQR, $125.4-$127.8); and PECARN, $125.8 million (IQR, $124.6-$127). CONCLUSIONS: The Rochester, Step-by-step, and PECARN criteria are the least costly when evaluating infants 29-90 days of age with a fever.

Population-based trends in hospitalizations due to injection drug use-related serious bacterial infections, Oregon, 2008 to 2018.

BACKGROUND: Injection drug use has far-reaching social, economic, and health consequences. Serious bacterial infections, including skin/soft tissue infections, osteomyelitis, bacteremia, and endocarditis, are particularly morbid and mortal consequences of injection drug use. METHODS: We conducted a population-based retrospective cohort analysis of hospitalizations among patients with a diagnosis code for substance use and a serious bacterial infection during the same hospital admission using Oregon Hospital Discharge Data. We examined trends in hospitalizations and costs of hospitalizations attributable to injection drug use-related serious bacterial infections from January 1, 2008 through December 31, 2018. RESULTS: From 2008 to 2018, Oregon hospital discharge data included 4,084,743 hospitalizations among 2,090,359 patients. During the study period, hospitalizations for injection drug use-related serious bacterial infection increased from 980 to 6,265 per year, or from 0.26% to 1.68% of all hospitalizations (P<0.001). The number of unique patients with an injection drug use-related serious bacterial infection increased from 839 to 5,055, or from 2.52% to 8.46% of all patients (P<0.001). While hospitalizations for all injection drug use-related serious bacterial infections increased over the study period, bacteremia/sepsis hospitalizations rose most rapidly with an 18-fold increase. Opioid use diagnoses accounted for the largest percentage of hospitalizations for injection drug use-related serious bacterial infections, but hospitalizations for amphetamine-type stimulant-related serious bacterial infections rose most rapidly with a 15-fold increase. People living with HIV and HCV experienced increases in hospitalizations for injection drug use-related serious bacterial infection during the study period. Overall, the total cost of hospitalizations for injection drug use-related serious bacterial infections increased from $16,305,129 in 2008 to $150,879,237 in 2018 (P<0.001). CONCLUSIONS: In Oregon, hospitalizations for injection drug use-related serious bacterial infections increased dramatically and exacted a substantial cost on the health care system from 2008 to 2018. This increase in hospitalizations represents an opportunity to initiate substance use disorder treatment and harm reduction services to improve outcomes for people who inject drugs.

Implementación del método de FilmArrayTM en pacientes pediátricos con infecciones severas / Implementation of the FilmArrayTM method in pediatric patients with severe infections / Implementação do método de matriz do FilmArrayTM em pacientes pediátricos com infecções graves

Se evaluó la implementación del método de PCR múltiple FilmArrayTM (Biofire Diagnostics, LLC, EE.UU.) en 21 niños con infección respiratoria aguda baja, 3 con meningoencefalitis, y un caso de sepsis. Se registraron el tiempo de demora hasta obtener el resultado y adecuar el tratamiento, los días de internación, los patógenos detectados y el costo de la incorporación de esta metodología. En los niños estudiados con FilmArrayTM el resultado estuvo disponible a los 90 minutos desde la toma de la muestra. Se detectaron patógenos no demostrados por los métodos disponibles, como Rhinovirus, además de diagnosticar coinfección viral; el tiempo promedio de estadía resultó 5 días. Se estimó reducir un 40% el costo global de internación. La implementación de FilmArrayTM resultó sencilla y se pudo incorporar a la sistemática de trabajo. Si bien esta experiencia incluyó un bajo número de pacientes, aportó información que demuestra el potencial de esta metodología para un mejor manejo del paciente crítico.

The implementation of multiple PCR FilmArrayTM (Biofire Diagnostics, LLC, USA) for 21 children with low acute respiratory infection, 3 with meningoencephalitis, and 1 case of sepsis was evaluated. Delay time until the result was obtained and the treatment adapted, hospitalization days, pathogens detected and the cost of incorporating this methodology were all recorded. In the children studied with FilmArrayTM the result was available 90 minutes after the sample was taken. Pathogens were not demonstrated by the available methods, such as Rhinovirus, apart from diagnosing viral coinfection, the average length of stay was 5 days. It was estimated to reduce the overall cost of hospitalization by 40%. The implementation of FilmArrayTM was simple and could be incorporated into the work system. Although this experience included a low number of patients, it provided information that demonstrates the potential of this methodology for better management of the critical patient.

Foi avaliada a implementação do método de PCR múltiplo FilmArrayTM (Biofire Diagnostics, LLC, EUA) em 21 crianças com infecção respiratória aguda baixa, 3 com meningoencefalite e um caso de sepse. O tempo de atraso foi registrado até a obtenção do resultado e a adaptação do tratamento, dias de internação, patógenos detectados e o custo da incorporação dessa metodologia. Nas crianças estudadas com o FilmArrayTM, o resultado ficou disponível 90 minutos após a coleta da amostra; foram detectados os patógenos não demonstrados pelos métodos disponíveis, como o Rinovírus, além de diagnosticar a coinfecção viral; o tempo médio de permanência foi de 5 dias. Foi estimado reduzir o custo total da hospitalização em 40%. A implementação do FilmArrayTM foi simples e pôde ser incorporada à sistemática de trabalho. Embora essa experiência tenha incluído um número de pacientes baixo, forneceu informações que demonstram o potencial dessa metodologia para um melhor gerenciamento do paciente crítico.

Assessment of the Risk Factors of Multidrug-Resistant Organism Infection in Adults With Type 1 or Type 2 Diabetes and Diabetic Foot Ulcer.

OBJECTIVES: To our knowledge, this is the first review to analyze the literature identifying risk factors for multidrug-resistant organism (MDRO) infection in patients with diabetic foot ulcer. The purpose of this study was to collect the currently published data to determine the most commonly and consistently identified risk factors for MDRO infection. METHODS: PubMed, MEDLINE, BIOSIS, Web of Science and the Cochrane Library electronic databases were searched. The last search updated was in September 2019. The evaluated outcomes included age, male sex, type of diabetes, diabetes duration, level of glycated hemoglobin, ulcer type, wound duration, ulcer size, ulcer grade, osteomyelitis, previous antibiotic therapy and previous hospitalization. The standard mean difference or the odds ratio (OR) was calculated for continuous or dichotomous data, respectively. The quality of the studies was assessed, and meta-analyses were performed with Cochrane Collaboration's RevMan 5.0 software. RESULTS: A total of 11 studies, including 1,229 patients provided evidence for 6 possible risk factors for MDRO infection. Ischemic ulcer (OR, 0.50; 95% confidence interval [CI], 0.35 to 0.71), ulcer size (standard mean difference, -0.27; 95% CI, -0.46 to -0.08), ulcer grade (OR, 0.36; 95% CI, 0.15 to 0.83), osteomyelitis (OR, 0.33; 95% CI, 0.25 to 0.45), previous antibiotic therapy (OR, 0.08; 95% CI, 0.04 to 0.14) and previous hospitalization (OR, 0.15; 95% CI, 0.08 to 0.28) were identified as risk factors for MDRO infection in patients with diabetic foot ulcer. CONCLUSIONS: Our meta-analysis indicated that ischemic ulcer, ulcer size, ulcer grade, osteomyelitis, previous antibiotic therapy and previous hospitalization were associated with MDRO infection in patients with diabetic foot ulcer.

Impact of infection on risk of Parkinson's disease: a quantitative assessment of case-control and cohort studies.

Identifying modifiable risk factors for Parkinson's disease (PD) to help prevent this disease has attracted increasing interest in recent years for the limited effective drugs at present. Despite many studies indicated that infection acts as a risk factor for PD, there is no quantitative assessment of the impact of viral and bacterial infections on the risk of developing PD. The present study performed a meta-analysis on the basis of 38 datasets from 13 studies covering 287,773 PD cases and 7,102,901 controls to ascertain the association between PD and infection and the differences in the strength of the viral and bacterial infections. The overall meta-analytic results indicated that individuals with infection had a 20% increased risk of PD compared with controls (OR 1.20, 95%CI 1.07-1.32). The subgroup analysis according to the type of infection found that bacterial infection had a significant impact on increased risk of PD (OR 1.40, 95%CI 1.32-1.48). The present analysis indicated that infection could increase the risk of developing PD, and physician should be aware of the risk of developing PD in subjects with infection.

Applicability of Sepsis-3 criteria and quick Sequential Organ Failure Assessment in patients with cirrhosis hospitalised for bacterial infections.

BACKGROUND & AIMS: An algorithm including Sepsis-3 criteria and quick Sequential Organ Failure Assessment (qSOFA) was recently proposed to predict severity of infection in cirrhosis. However, its applicability among patients without a baseline SOFA available for Sepsis-3 definition is unknown. We sought to investigate the applicability and prognostic value of qSOFA and Sepsis-3 criteria in patients with cirrhosis hospitalised for bacterial infections, without pre-hospitalisation SOFA. METHODS: In this cohort study, 164 patients were followed up to 30 days. Data collection, including the prognostic models, was performed at admission and at day-3. RESULTS: All patients fulfilled Sepsis-3 criteria (admission SOFA ≥ 2) and, therefore, admission Sepsis-3 was not included in further analysis. Admission qSOFA was an independent predictor of survival (HR = 2.271, P = 0.015). For patients initially classified as high risk by qSOFA, Chronic Liver Failure - Sequential Organ Failure Assessment (CLIF-SOFA) was the only prognostic predictor. Among patients initially classified as low risk by qSOFA, the following parameters evaluated at day-3 were independent predictors of survival: qSOFA, acute-on-chronic liver failure, and Child-Pugh classification. Although not independently related to survival, Sepsis-3 criteria at day-3 was associated with lower 30-day survival in Kaplan-Meier analysis (66% vs 85%, P = 0.008). However, prognosis was better predicted by day-3 qSOFA, with 30-day Kaplan-Meier survival probability of 88% when qSOFA < 2 and 24% among those with qSOFA ≥ 2. CONCLUSION: Sepsis-3 criteria evaluated at admission are very limited in infected patients with cirrhosis without baseline SOFA. qSOFA was independently related to survival and appears to be a valuable tool for determining severity of infection and to follow patients initially classified as low risk.

Cost-effectiveness analysis comparing ceftazidime/avibactam (CAZ-AVI) as empirical treatment comparing to ceftolozane/tazobactam and to meropenem for complicated intra-abdominal infection (cIAI).

Background: The rising incidence of resistance to currently available antibiotics among pathogens, particularly Gram-negative pathogens, in complicated intra-abdominal infections (cIAIs) has become a challenge for clinicians. Ceftazidime/avibactam (CAZ-AVI) is a fixed-dose antibiotic approved in Europe and the United States for treating (in combination with metronidazole) cIAI in adult hospitalised patients who have limited or no alternative treatment options. The approval was based on the results of RECLAIM, a Phase III, parallel-group, comparative study (RECLAIM 1 [NCT01499290] and RECLAIM 2 [NCT01500239]). The objective of our study was to assess the cost-effectiveness of CAZ-AVI plus metronidazole compared with 1) ceftolozane/tazobactam plus metronidazole and 2) meropenem, as an empiric treatment for the management of cIAI in Italy. Methods: A sequential, patient-level simulation model, with a 5-year time horizon and 3% annual discount rate (applied to both costs and health benefits), was developed using Microsoft Excel® to demonstrate the clinical course of the disease. The impact of resistant pathogens was included as an additional factor. Results: In the base-case analysis, the CAZ-AVI sequence (CAZ-AVI plus metronidazole followed by a colistin + tigecycline + high-dose meropenem combination after treatment failure), when compared to sequences for ceftolozane/tazobactam (ceftolozane/tazobactam plus metronidazole followed by colistin + tigecycline + high-dose meropenem after treatment failure) and meropenem (meropenem followed by colistin + tigecycline + high-dose meropenem after treatment failure), had better clinical outcomes with higher cure rates (93.04% vs. 91.52%; 92.98% vs. 90.24%, respectively), shorter hospital stays (∆ = - 0.38 and ∆ = - 1.24 days per patient, respectively), and higher quality-adjusted life years (QALYs) gained per patient (4.021 vs. 3.982; 4.019 vs. 3.960, respectively). The incremental cost effectiveness ratio in the CAZ-AVI sequence was €4099 and €15,574 per QALY gained versus each comparator sequence, respectively, well below the willingness-to-pay threshold of €30,000 per QALY accepted in Italy. Conclusions: The model results demonstrated that CAZ-AVI plus metronidazole could be a cost-effective alternative when compared with other antibiotic treatment options, as it is expected to provide better clinical benefits in hospitalised patients with cIAI in Italy.

Diabetes Shared Care Program (DSCP) and risk of infection mortality: a nationwide cohort study using administrative claims data in Taiwan.

OBJECTIVE: The Diabetes Shared Care Program (DSCP) is an integrated care model in Taiwan that has been proven to improve the care quality of patients with diabetes. We aimed to evaluate the efficacy of DSCP in decreasing the hospital mortality of infectious diseases. METHODS: From 1 662 929 patients with type 2 diabetes newly diagnosed between 1999 and 2013, we retrieved a total of 919 patients who participated in the DSCP with the first hospitalisation for an infectious disease as the study cohort and 9190 propensity score-matched patients with type 2 diabetes who did not participate as the comparison.The efficacy of DSCP was evaluated via the following comparisons between the DSCP and non-DSCP cohorts: hospital mortality, 1-year medical cost prior to and during the hospitalisation, and complications, such as receiving mechanical ventilation and intensive care unit admission. The ratio (OR) for hospital mortality of the DSCP participants was calculated by logistical regression. Further stratification analyses were conducted to examine which group of patients with type 2 diabetes benefited the most from the DSCP during hospitalisation for infectious diseases. RESULTS: The DSCP cohort had a lower hospital mortality rate than the non-DSCP participants (2.18% vs 4.82%, p<0.001). The total medical cost during the hospitalisation was lower in the DSCP cohort than in the non-DSCP cohort (NT$72 454±30 429 vs NT$86 385±29 350) (p=0.006). In the logistical regression model, the DSCP participants exhibited a significantly decreased adjusted OR for hospital mortality (adjusted OR=0.42, 95% CI 0.26 to 0.66, p=0.0002). The efficacy of the DSCP was much more prominent in male patients with type 2 diabetes and in patients with lower incomes. CONCLUSION: Participation in the DSCP was associated with a lower risk of hospital mortality for infectious diseases.

Molecular and culture based assessment of bacterial pathogens in subjects with diabetic foot ulcer.

INTRODUCTION: Expeditious and precise discerning of bacterial pathogens is a fundamental grail, of clinical diagnostic microbiology. Genotypic detection is a budding substitute to recognize phenotypic culture based processes in bacterial identification. AIMS: We report a comparative evaluation of biochemical and genomic-based assays for exploring the commonest bacterial flora of infected diabetic foot ulcers along with clinical variables of subjects enrolled. METHODS: The pathogens selected (i) Staphylococcus aureus ii) Pseudomonas aeruginosa, iii) Escherichia coli and iv) Klebsiella pneumonia, stood for the most frequent isolates of diabetic foot infection in previous studies from Northern India. Identification of these pathogens were done by conventional assays and polymerase chain reaction. RESULTS: Of 50 specimens obtained from infected DFUs, 74% of cases were affirmative by bacteriological assays and 90% showed positivity via polymerase chain reaction (PCR). Among processed samples 44 isolates were detectable through phenotypic analysis and 65 bacteria by species-specific PCR. Thirteen samples and 21 isolates could not be scrutinized by phenotypic identification systems. The most prevalent pathogens identifiable were Klebsiella pneumonia, followed by Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli. CONCLUSIONS: We have shown that PCR-based diagnostic methods improved the identification compared to conventional methods and highlight the incorporation of PCR due to shorten turnaround time translating into improved clinical outcomes.

Inpatient versus outpatient parenteral antibiotic therapy at home for acute infections in children: a systematic review.

Inpatient management is necessary in many situations, but medical and allied-health treatments are increasingly being used on an outpatient basis to allow patients who would traditionally have been admitted to hospital to remain at home. Home-based clinical management has many potential benefits, including reduced hospital-acquired infections, cost savings, and patient and family satisfaction. Studies in adults provide evidence for the benefits of home-based versus hospital-based intravenous antibiotics, but few studies inform practice in home-based intravenous antibiotic therapy for children. We systematically reviewed the efficacy, safety, satisfaction, and cost of home-based versus hospital-based intravenous antibiotic therapy for acute infections in children. We searched MEDLINE (from Jan 1, 1946, to Jan 31, 2017) and Embase (from Jan 1, 1974, to Jan 31, 2017) for studies investigating home-based and hospital-based intravenous antibiotic therapy and assessed them for quality. 2827 articles were identified and 19 studies were included in the systematic review. Efficacy results differed between studies depending on the outcome assessed. The incidence of complications and readmission to hospital was similar for hospital-based and home-based treatments. In seven (47%) of 15 studies, patients who had all or part of their treatment at home received treatment for longer than patients who were treated entirely in hospital. No studies showed that home-based treatment was less safe than hospital-based treatment. In all studies in which treatment satisfaction or costs were assessed, home-based treatment was satisfactory to patients or patients' families and less expensive per episode than hospital-based treatment by 30-75%. Thus, home-based intravenous antibiotic therapy might be popular and cost-effective, but randomised studies of the efficacy of this strategy are needed. This systematic review was registered with PROSPERO (number CRD42015024406).

Assessment of Sepsis-3 criteria and quick SOFA in patients with cirrhosis and bacterial infections.

INTRODUCTION: Patients with cirrhosis have a high risk of sepsis, which confers a poor prognosis. The systemic inflammatory response syndrome (SIRS) criteria have several limitations in cirrhosis. Recently, new criteria for sepsis (Sepsis-3) have been suggested in the general population (increase of Sequential Organ Failure Assessment (SOFA) ≥2 points from baseline). Outside the intensive care unit (ICU), the quick SOFA (qSOFA (at least two among alteration in mental status, systolic blood pressure ≤100 mm Hg or respiratory rate ≥22/min)) was suggested to screen for sepsis. These criteria have never been evaluated in patients with cirrhosis. The aim of the study was to assess the ability of Sepsis-3 criteria in predicting in-hospital mortality in patients with cirrhosis and bacterial/fungal infections. METHODS: 259 consecutive patients with cirrhosis and bacterial/fungal infections were prospectively included. Demographic, laboratory and microbiological data were collected at diagnosis of infection. Baseline SOFA was assessed using preadmission data. Patients were followed up until death, liver transplantation or discharge. Findings were externally validated (197 patients). RESULTS: Sepsis-3 and qSOFA had significantly greater discrimination for in-hospital mortality (area under the receiver operating characteristic (AUROC)=0.784 and 0.732, respectively) than SIRS (AUROC=0.606) (p<0.01 for both). Similar results were observed in the validation cohort. Sepsis-3 (subdistribution HR (sHR)=5.47; p=0.006), qSOFA (sHR=1.99; p=0.020), Chronic Liver Failure Consortium Acute Decompensation score (sHR=1.05; p=0.001) and C reactive protein (sHR=1.01;p=0.034) were found to be independent predictors of in-hospital mortality. Patients with Sepsis-3 had higher incidence of acute-on-chronic liver failure, septic shock and transfer to ICU than those without Sepsis-3. CONCLUSIONS: Sepsis-3 criteria are more accurate than SIRS criteria in predicting the severity of infections in patients with cirrhosis. qSOFA is a useful bedside tool to assess risk for worse outcomes in these patients. Patients with Sepsis-3 and positive qSOFA deserve more intensive management and strict surveillance.

Guillain-Barré Syndrome.

Guillain-Barré syndrome is an acute inflammatory immune-mediated polyradiculoneuropathy presenting typically with tingling, progressive weakness, and pain. Variants and formes frustes may complicate recognition. The best known variant is the sensory ataxic form of Miller Fisher syndrome, which also affects the oculomotor nerves and the brain stem. Divergent pathologic mechanisms lead to demyelinating, axonal, or mixed demyelinating-axonal damage. In the demyelinating form, yet to be identified antigens are inferred by complement activation, myelin destruction, and macrophage-activated cleanup. In the axonal and Miller Fisher variants, gangliosides (GM1, GD1a, GQ1b) are targeted by immunoglobulins and share antigenic epitopes with some bacterial and viral antigens. Campylobacter jejuni infection is associated with an axonal-onset variant; affected patients commonly experience more rapid deterioration. Many other antecedent infectious agents have been recognized including the most recently identified, Zika virus. Supportive care remains the mainstay of therapy. Plasma exchange or intravenous immunoglobin hastens recovery. Combination immunotherapy is not more effective, and the efficacy of prolonged immunotherapy is unproven. One in 3 patients will have deterioration severe enough to require prolonged intensive care monitoring or mechanical ventilation. Full recovery is often seen; most patients regain ambulation, even in severe cases, but disability remains in up to 10% and perhaps more. Numerous challenges remain including early identification and control of infectious triggers, improved access of modern neurointensive care worldwide, and translating our understanding of pathogenesis into meaningful preventive or assistive therapies. This review provides a historical perspective at the centenary of the first description of the syndrome, insights into its pathogenesis, triage, initial immunotherapy, and management in the intensive care unit.

Population Pharmacokinetics of Piperacillin in Nonobese, Obese, and Morbidly Obese Critically Ill Patients.

The treatment of infections in critically ill obese and morbidly obese patients is challenging because of the combined physiological changes that result from obesity and critical illness. The aim of this study was to describe the population pharmacokinetics of piperacillin in a cohort of critically ill patients, including obese and morbidly obese patients. Critically ill patients who received piperacillin-tazobactam were classified according to their body mass index (BMI) as nonobese, obese, and morbidly obese. Plasma samples were collected, and piperacillin concentrations were determined by a validated chromatographic method. Population pharmacokinetic analysis and Monte Carlo dosing simulations were performed using Pmetrics software. Thirty-seven critically ill patients (including 12 obese patients and 12 morbidly obese patients) were enrolled. The patients' mean ± standard deviation age, weight, and BMI were 50 ± 15 years, 104 ± 35 kg, and 38.0 ± 15.0 kg/m2, respectively. The concentration-time data were best described by a two-compartment linear model. The mean ± SD parameter estimates for the final covariate model were a clearance of 14.0 ± 7.1 liters/h, a volume of distribution of the central compartment of 49.0 ± 19.0 liters, an intercompartmental clearance from the central compartment to the peripheral compartment of 0.9 ± 0.6 liters · h-1, and an intercompartmental clearance from the peripheral compartment to the central compartment of 2.3 ± 2.8 liters · h-1 A higher measured creatinine clearance and shorter-duration infusions were associated with a lower likelihood of achieving therapeutic piperacillin exposures in patients in all BMI categories. Piperacillin pharmacokinetics are altered in the presence of obesity and critical illness. As with nonobese patients, prolonged infusions increase the likelihood of achieving therapeutic concentrations.

Acute focal bacterial nephritis in a cohort of hospitalized adult patients with acute pyelonephritis. Assessment of risk factors and a predictive model.

BACKGROUND: Acute focal bacterial nephritis (AFBN) is a complicated form of acute pyelonephritis (APN) characterized by single or multiple areas of localised infection in the kidney without liquefaction or abscess. Studies investigating AFBN in adults are scarce. AIM: The present study was aimed at evaluating the prevalence, associated factors, and presence of atypical clinical and radiological manifestations in adult AFBN patients. Also, we developed a clinical prediction model to evaluate the probability of AFBN in patients with APN. METHODS: The clinical records of 377 patients (mean age 54years, 74.0% females) admitted to a hospital over a 5-year period with APN were reviewed. RESULTS: A total of 57 cases of AFBN were radiologically identified (prevalence, 15.1%). Patients with AFBN were younger and displayed atypical manifestations more frequently than patients without AFBN; these included both clinical and radiological (pleural effusion, gallbladder wall thickening, fluid around the gallbladder, perirenal fluid, and ascites) manifestations. Patients with AFBN showed lower systolic blood pressure and needed more days of therapy to become afebrile, longer total duration of antibiotic therapy, and longer hospital stay than patients without AFBN. Contraceptive use was more frequent in patients with AFBN. A model based on five clinical variables showed good discrimination performance for the diagnosis of AFBN (Area under the curve, 0.77 (95% CI, 0.69-0.89)). CONCLUSIONS: Patients with AFBN frequently present with atypical clinical and radiological manifestations. Clinical presentation by means of a predictive model may predict the presence of AFBN. Patients with AFBN need more intensive therapy, which is followed by a favourable outcome.