Discontinuation Of Antibiotic Therapy Research Articles

Antimicrobial Stewardship for Ventilator Associated Pneumonia in Intensive Care (the ASPIC trial): study protocol for a randomised controlled trial

IntroductionVentilator-associated pneumonia (VAP) remains the leading cause of infections treated in the intensive care units (ICU). In a personalised care approach, we hypothesise that the duration of treatment of VAP...

Pyogenic spondylitis due to Streptococcus agalactiae with paraspinal abscess and vertebral destruction in a diabetic patient: time course of imagings.

A 76-year-old female with type 2 diabetes mellitus presented with hematuria, low back pain, and intermittent fever for 7 days. She was admitted to our hospital and diagnosed with Streptococcus agalactiae (GBS) bacteremia. CT showed an air density within the right iliopsoas muscle, and an MRI of the spine revealed hyperintensity in the right half of the L1-L2 intervertebral disk, leading to the diagnosis of a paraspinal abscess and L1-L2 pyogenic spondylitis. Antibiotic therapy was started and the clinical symptoms, as well as serologic biomarkers and radiologic images of the paraspinal abscess, were improved. The therapy was stopped on day 72 despite vertebral destruction progression. Vertebral endplate ossification was observed on day 108, and further bone formation was noted on day 177. Our case study with radiologic findings over 6 months demonstrated how bone destruction with pyogenic spondylitis, which had been treated with antibiotic therapy, improved after cessation of antibiotics. Although GBS is a rare cause of spondylitis, diabetic mellitus is a risk factor for the development of invasive GBS infections, especially under poor glycemic control. Bone destruction of pyogenic spondylitis can improve after discontinuation of antibiotic therapy. It may be important to decide the period of antibiotic therapy based on clinical conditions, serologic biomarkers, and soft tissue findings rather than bone findings. When elderly diabetic patients present with back pain and fever, spondylitis should be considered in the differential diagnosis to avoid potential diagnostic delays or misdiagnosis.

Changes in the Oxidation-Reduction State of Human Dermal Fibroblasts as an Effect of Lomefloxacin Phototoxic Action.

Phototoxicity induced by antibiotics is a real problem in health care. The discontinuation of antibiotic therapy due to a phototoxic reaction can lead to the development of resistant strains. Fluoroquinolones are widely used antibiotics that exhibit phototoxic activity under UVA radiation. The purpose of the study was to examine the redox status of human dermal fibroblasts exposed to UVA radiation and treated with lomefloxacin, the most phototoxic fluoroquinolone. Lomefloxacin alone was found to have an antiproliferative activity on fibroblasts by affecting the cell cycle. In addition, the drug caused a redox imbalance associated with the decreased expression of catalase and glutathione peroxidase. UVA radiation increased the drug cytotoxicity and oxidative stress induced by lomefloxacin. The decrease in cell viability was accompanied by a high level of reactive oxygen species and extensive changes in the antioxidant levels. The revealed data indicate that the phototoxic action of lomefloxacin results from both increased reactive oxygen species production and an impaired antioxidant defense system. Considering all of the findings, it can be concluded that lomefloxacin-induced phototoxic reactions are caused by an oxidoreductive imbalance in skin cells.

The Impact of Gastrointestinal PCR on the Management of Gastrointestinal Infections in Immunocompromised Patients

Introduction: Gastrointestinal infections are one of the leading causes of morbidity and mortality throughout the world, particularly in the immunocompromised. Gastrointestinal PCR appears to be the technique of choice for establishing the molecular diagnosis of pathogenic gastrointestinal agents. The aim of this study was to establish the epidemiological, clinical and evolutionary profile of gastrointestinal infections and to study the impact of molecular diagnosis on the choice of a targeted therapy. Methods: This is a retrospective study carried out in the Microbiology Department of Arrazi Hospital of the Mohamed VI University Hospital Center, including all immunocompromised patients treated for a gastrointestinal infection and needing a hospitalization in the various departments, over a period of 15 months. Results: During the period studied, 124 patients were collected. The average age of the patients was 22 years. Signs of gastrointestinal infection were present in all patients. Of the patients sampled, 95.2% received probabilistic antibiotic therapy. Gastrointestinal infection has been documented in 57.26% of patients. A bacterial etiology was found in 76.81% of patients. A viral etiology was found in 13.04% of the patients and a parasitic etiology was found in 10.15% of the patients. Enteropathogenic E. coli was the most common infectious agent detected (19.53%). Co-infections were found in 29.84% of patients. Following PCR results, management was changed in 70 patients (56.45%), including initiation or modification of antibiotics in 40 patients (32.26%) and discontinuation of antibiotic therapy in 30 patients (24.19%). Conclusion: The diagnosis of gastrointestinal infections by multiplex PCR allowed us to provide optimal patient care with a reduction in the unnecessary use of antibiotics and an improvement in the course of care.

Safety and Efficacy of Nafcillin for Empiric Therapy of Late-Onset Sepsis in the NICU.

In 2014 at Nationwide Children's Hospital, the Neonatal Antimicrobial Stewardship Program recommended nafcillin over vancomycin for empirical therapy of possible late-onset sepsis (LOS) in infants without a history of methicillin-resistant Staphylococcus aureus colonization or infection. We report our experience with this guideline and assess its safety. We retrospectively reviewed all infants who received nafcillin or vancomycin for empirical treatment of possible LOS at 3 NICUs before (January 2013-May 2014) and after (January 2017-March 2019) implementation of a vancomycin reduction guideline. Safety measures included duration of blood culture positivity, recurrence of infection with the same previously identified pathogen in the 14 days after discontinuation of antibiotic therapy, and mortality. Among 366 infants who received a first antibiotic course for possible LOS, 84% (95 of 113) and 25% (62 of 253) received empirical therapy with vancomycin before and after the guideline implementation, respectively, representing a 70% reduction. Nafcillin use increased by 368%. Duration of blood culture positivity did not differ before and after the guidance. In 2 infants, antibiotic therapy was restarted within 14 days of discontinuation of the initial therapy for recurrence of the same infection; both had received empirical vancomycin. Overall in-hospital mortality was 10%, and there was no difference before (9%) and after (10%) implementation of the vancomycin reduction guidance (odds ratio, 0.97). Nafcillin can be a safe alternative to vancomycin for empirical therapy of LOS among NICU infants who do not have a history of methicillin-resistant S aureus infection or colonization.

1424. Short-Course Antibiotic Therapy for Urinary Tract Infection (UTI) in the NICU: It’s Safe and Effective!

Abstract Background Antibiotic overuse in the neonatal intensive care unit (NICU) has been associated with adverse patient outcomes such as necrotizing enterocolitis (NEC), late-onset sepsis, invasive candidiasis, bronchopulmonary dysplasia, neurodevelopmental impairment, and death. On 11/2020 at Nationwide Children’s Hospital, Columbus, OH, the Neonatal Antimicrobial Stewardship Program Committee recommended 5 days of antibiotic therapy with a subsequent antibiotic “timeout” for uncomplicated UTI without bacteremia as part of ongoing efforts to reduce antibiotic exposure among high risk infants in 7 Level 2/3/4 NICUs. Methods Retrospective review of all infants who received antimicrobial therapy for UTI after implementation of a UTI Diagnosis and Management Protocol. Twice weekly NEO-ASP meetings provided prospective audit and feedback to neonatologists on appropriate antibiotic therapy and duration. Pertinent clinical, laboratory, and outcome data were obtained from the infants’ electronic health record. Safety measure evaluated include recurrence of infection with the same previously identified pathogen in the fourteen days after discontinuation of antibiotic therapy and mortality. Results Since implementation of the UTI protocol, 28 infants (median gestational age, 28 wk [IQR, 26-30 wk; median birth weight, 1203 g [IQR, 731-1801 g]) received antimicrobial therapy for treatment of a UTI at a median age of 50 days (IQR, 28-69 days). The most frequent pathogens were E. coli (n=8), K. pneumoniae (n=5), and Enterobacter spp. (n=4). Median duration of antibiotic therapy was 6 calendar days (IQR, 5-6 days). Only 1 (4%) infant had antibiotic therapy restarted within 14 days of discontinuation of initial therapy; infant had fever but blood, urine, and CSF cultures were sterile and antibiotic therapy was discontinued after 48 hours. One (4%) infant (23 wk gestational age) died at 6 weeks of age from NEC totalis not related to the previous UTI. 22 (81%) infants have been discharged home while 6 remain in the NICU. Conclusion Our preliminary data suggests that short course antibiotic therapy (with a timeout) < ![if !supportAnnotations] >[SP1]< ![endif] > for uncomplicated UTIs in the NICU is an effective and safe therapy that ultimately may lead to less antibiotic exposure among high risk infants. Disclosures All Authors: No reported disclosures

A modified Delphi approach to develop a trial protocol for antibiotic de-escalation in patients with suspected sepsis.

Early administration of antibiotics in sepsis is associated with improved patient outcomes, but safe and generalizable approaches to de-escalate or discontinue antibiotics after suspected sepsis events are unknown. We used a modified Delphi approach to identify safety criteria for an opt-out protocol to guide de-escalation or discontinuation of antibiotic therapy after 72 hours in non-ICU patients with suspected sepsis. An expert panel with expertise in antimicrobial stewardship and hospital epidemiology rated 48 unique criteria across 3 electronic survey rating tools. Criteria were rated primarily based on their impact on patient safety and feasibility for extraction from electronic health record review. The 48 unique criteria were rated by anonymous electronic survey tools, and the results were fed back to the expert panel participants. Consensus was achieved to either retain or remove each criterion. After 3 rounds, 22 unique criteria remained as part of the opt-out safety checklist. These criteria included high-risk comorbidities, signs of severe illness, lack of cultures during sepsis work-up or antibiotic use prior to blood cultures, or ongoing signs and symptoms of infection. The modified Delphi approach is a useful method to achieve expert-level consensus in the absence of evidence suifficient to provide validated guidance. The Delphi approach allowed for flexibility in development of an opt-out trial protocol for sepsis antibiotic de-escalation. The utility of this protocol should be evaluated in a randomized controlled trial.

Development of pathogenetically justified approaches to therapy of young children with acute respiratory infections requiring antibacterial drugs

The purpose of the study: to evaluate the protective properties of a multi-strain probiotic in the development of gastrointestinal disorders with impaired microbiota during antibiotic therapy (ABT) for 1 to 3 years old children with acute respiratory infection (ARI). Objectives of research: to evaluate the incidence of development and severity of gastrointestinal disorders, as well as changes in the dynamics of intestinal microbiota using 16S rRNA gene sequencing in 1 to 3 years old children with ARI and receiving ABT, depending on the addition of a multi-strain probiotic to the treatment regimen. Materials and methods: the study involved 148 children from 1 to 7 years old both girls and boys (54 children were 1 to 3 y.o. and 65 were 3 to 7 y.o.), hospitalized within first 3 days of URTI symptoms (acute upper respiratory tract infection – URTI) and 29 healthy children from outpatient department as a healthy control. Present article covers data and outcomes of younger age group – 54 children 1 to 3 years old, hospitalized within first 3 days of illness and 10 healthy children of the same age range. The main group included 27 children who received ABT + multi-strain probiotic Bac-Set® Baby for the entire period of ABT and extra 14 days after its discontinuation; the comparison group included 27 children who received only ABT. The frequency of bowel movements was assessed, feces were evaluated accordingly to Bristol scale upon admission to the hospital, befor e discharge from the hospital (in 7 ± 2 days), and in 21 ± 2 days from the beginning of ABT. Results. The frequency of bowel movements after 7 ± 2 days and 21 ± 2 days from the start of therapy was significantly higher in the comparison group than in the main group (81.5% and 26% versus 7.4% and 7.4%, respectively). The stool rate accordingly to Bristol scale in the comparison group changed up to moderate diarrhea, which was not registered in the main group. In both groups, an increase in alpha-diversity of microbiota was observed within 2-week period after discontinuation of antibiotic therapy. During the study, adverse reactions of multi-strain probiotic were not found. Conclusions. The results allow to suggest that the use of Bac-Set® Baby multistrain probiotic helps to maintain the stability of the microbiome during antibiotic therapy and in the recovery period after it. The use of Bac-Set® Baby with antibacterial therapy has a protective effect on gastrointestinal upsets incidence rate and reduces the negative impact on microbiome.

Discontinuation of antibiotic therapy within 24 hours of treatment initiation for patients with no clinical evidence of bacterial infection: a 5-year safety and outcome study from Singapore General Hospital Antimicrobial Stewardship Program

BackgroundOverprescribing antibiotics for patients with no bacterial infection is of growing global concern. It is important for timely Antimicrobial Stewardship Program (ASP) intervention to discontinue antibiotics for patients whose symptoms can be explained by non-infective causes, and without availability of bacterial cultures and susceptibilities reports. This study aimed to evaluate clinical outcomes and safety of early ASP review in these patients. MethodsA retrospective review of the ASP database (January 2010 to December 2014) was conducted to identify patients for whom ASP recommended discontinuation of empiric antibiotics within 24 hours of prescribing. Demographics were collected. Clinical outcomes – duration of therapy, length of hospital stay (LOS), infection-related readmissions, and all-cause mortality – were compared between interventions accepted and rejected groups. Continuous data were analysed via unpaired Student's t-test. Categorical data were analysed using χ2 test or Fisher's exact test, as appropriate. ResultsThe ASP team recommended 794 interventions (overall acceptance rate of 72.9%, 579 of 794). There were no significant between-group differences in underlying demographics, and Charlson comorbidity index score. However, the interventions acceptance group had significantly shorter duration of therapy by 2.61 days (2.72 ± 3.04 vs. 5.33 ± 2.54 days; P < 0.01) and LOS by 7.41 days (7.98 ± 13.14 vs. 15.39 ± 22.62 days; P < 0.01), with estimated cost savings of SGD10 817 per patient. There were no significant between-group differences in 14-day mortality and readmission rates. ConclusionPrompt ASP interventions at Singapore General Hospital were associated with significant reductions in duration of therapy and LOS, with cost savings. It was demonstrated that it is safe to discontinue antibiotics within 24 hours of prescribing for patients with no evidence of bacterial infections.

Impact of an antimicrobial stewardship program at a university hospital of respiratory diseases

Background: Antimicrobial Stewardship Programs (ASP's) have the potential to reduce antimicrobial exposure and decrease microbial resistance, and to decrease costs. The objective of this study was to characterize the overall impact of an ASP on antimicrobial utilization, antimicrobial resistance and mortality rates. Methods & Materials: Quasi-experimental study, before and after ASP implementation, from January to May 2016 and from January to May 2017 respectively, in an 8-bed adult intensive care unit at a university hospital of respiratory diseases. ASP included: elaboration of local guides (LG's); empiric therapy according to LG's; taking cultures before starting antibiotic therapy (AT); de-escalation of therapy as soon as culture results were available; discontinuation of AT if evidence of infection was absent; short courses of AT. Outcomes for analyses included: retrospective data for antimicrobial utilization measured as defined daily doses (DDD); bacterial susceptibilities of the first five most frequent organisms isolated in each period; and mortality rates for all causes and for infectious causes according to ICD-10 classification. Results: The overall reduction of all antibiotic utilization was 19%, including a decrease by 81% in meropenem use, 11% for imipenem, 39% for ciprofloxacin, 93% for ceftriaxone, 23% for ceftazidime and 33% for vancomycin. The most frequently isolated organism in the ASP period were Pseudomonas aeruginosa, with a reduction by 50% of Acinetobacter baumanii, the most frequent isolation in the pre-ASP period. Pseudomonas aeruginosa showed resistance to ceftazidime and cefepime in 55% of the cases in the pre-ASP period, whereas only 5% were resistant to the same antibiotics in the ASP period. The susceptibility pattern of Klebsiella pneumoniae in the pre-ASP period was 50% KPC and 83% ESBL, in the ASP period there was no carbapenem resistance and 75% ESBL. There was a 71% reduction in overall mortality rates and a 35% reduction in mortality due to infectious causes in the ASP period. Conclusion: There were limitations in this study due to missing individual patient data. There is a trend towards a decrease in the utilization of antibiotics and a shift of the epidemiological and susceptibility patterns of multidrug resistance organisms. The implementation of ASP was not accompanied by an increase in mortality.

Therapy and Outcome of Staphylococcus aureus Infections of Intracorporeal Ventricular Assist Devices.

Infection of the driveline or pump pocket is a common complication in patients with ventricular assist devices (VADs) and Staphylococcus aureus is the main pathogen causing such infections. Limited evidence is currently available to guide the choice of antibiotic therapy and the duration of treatment in these patients. Patients at the University Medical Center Utrecht who developed a VAD‐related S. aureus infection between 2007 and 2016 were retrospectively assessed. Blood culture isolates were typed by whole genome sequencing to differentiate between relapses and reinfections, and to determine whether antibiotic therapy had led to acquisition of resistance mutations. Twenty‐eight patients had S. aureus VAD infections. Ten of these patients also suffered S. aureus bacteremia. Discontinuation of antibiotic therapy was followed by relapse in 50% of the patients without prior S. aureus bacteremia and in 80% of patients with bacteremia. Oral cephalexin could ultimately suppress the infection for the duration of follow‐up in 8/8 patients without S. aureus bacteremia and in 3/6 patients with S. aureus bacteremia. Clindamycin failed as suppressive therapy in 4/4 patients. Cephalexin appears an adequate choice for antibiotic suppression of VAD infections with methicillin‐susceptible S. aureus. In patients without systemic symptoms, it may be justified to attempt to stop therapy after treatment of the acute infection, but antibiotic suppression until heart transplant seems indicated in patients with S. aureus bacteremia.

Clinical Manifestations and Outcomes of Fluoroquinolone-Related Acute Interstitial Nephritis

ObjectiveTo describe the clinical presentation, diagnosis, and outcomes of patients with biopsy-proven acute interstitial nephritis (AIN) related to fluoroquinolone (FQ) therapy. Patient and MethodsWe conducted a retrospective review of biopsy-proven AIN attributed to FQ use at Mayo Clinic's campus in Rochester, Minnesota, from January 1, 1993, through December 31, 2016. Cases were reviewed by a renal pathologist and attributed to FQ use by an expert nephrologist. We also reviewed and summarized all published case reports of biopsy-proven AIN that were attributed to FQ use. ResultsWe identified 24 patients with FQ-related biopsy-proven AIN at our institution. The most commonly prescribed FQ was ciprofloxacin in 17 patients (71%), and the median antibiotic treatment duration was 7 days (interquartile range [IQR], 5-12 days). The median time from the initiation of FQ to the diagnosis of AIN was 8.5 days (IQR, 3.75-20.75 days). Common clinical manifestations included fever (12; 50%), skin rash (5; 21%), and flank pain (2; 8%), and 9 (38%) had peripheral eosinophilia. However, 4 (17%) of the patients were asymptomatic at the time of diagnosis and AIN was suspected on the basis of routine laboratory monitoring. Most patients (17; 71%) recovered after the discontinuation of antibiotic therapy, and renal function returned to baseline at a median of 20.5 days (IQR, 11.75-27.25 days). Six patients (25%) required temporary hemodialysis, and 14 patients (58%) received corticosteroid therapy. ConclusionThe onset of FQ-related AIN can be delayed, and a high index of suspicion is needed by physicians evaluating these patients. Overall outcomes are favorable, with recovery to baseline renal function within 3 weeks of discontinuing the offending drug.

The STOP-AB trial protocol: efficacy and safety of discontinuing patient antibiotic treatment when physicians no longer consider it necessary

IntroductionSince 2011, the Spanish Society of Family Medicine has recommended general practitioners (GPs) to ask their patients to stop taking antibiotics when they suspect a viral infection. However, this practice...

Perforated Appendicitis: Nurse Practitioner Follow-Up Telephone Calls Reducing Unplanned Return to Care With/Without Readmission

TOPIC This is about the impact of nurse practitioner (NP) telephone follow-up in the prevention of unplanned return to care for patients with perforated appendicitis. Background Perforated appendicitis is a high-volume diagnosis managed by NPs in the ambulatory surgical clinic at the Boston Children’s Hospital. Patients’ symptoms and well-being are routinely assessed with serial follow-up telephone calls while on home antibiotic therapy to coordinate extension or discontinuation of antibiotic therapy. Patients received a telephone call by an NP within 2 business days. The intent of the call is to assess the patient’s current clinical status through an in-depth symptom analysis, clarify antibiotic therapy, reinforce discharge education, and answer questions. It also allows the NP to determine if an interim NP appointment is needed. Method and Design Population: This shows a retrospective chart review of pediatric patients with a diagnosis of perforated appendicitis undergoing home antibiotic therapy. Inclusion Criteria The following are the inclusion criteria: patients diagnosed with perforated appendicitis and discharged home on intravenous and oral antibiotic therapy. Data Analysis Data regarding patient receipt of telephone call—collection of symptom analysis, antibiotic regimen, and patient well-being—were collected. Data will be used to assess if preventative telephone follow-up by NPs and the provision of anticipatory patient/family education may lead to the earlier detection and management of potential complications. Conclusion An NP follow-up telephone call may help reduce the total number of unplanned emergency department visits and, potentially, hospital readmission.

Role of biomarkers in the management of antibiotic therapy: an expert panel review II: clinical use of biomarkers for initiation or discontinuation of antibiotic therapy

Biomarker-guided initiation of antibiotic therapy has been studied in four conditions: acute pancreatitis, lower respiratory tract infection (LRTI), meningitis, and sepsis in the ICU. In pancreatitis with suspected infected necrosis, initiating antibiotics best relies on fine-needle aspiration and demonstration of infected material. We suggest that PCT be measured to help predict infection; however, available data are insufficient to decide on initiating antibiotics based on PCT levels. In adult patients suspected of community-acquired LRTI, we suggest withholding antibiotic therapy when the serum PCT level is low (<0.25 ng/mL); in patients having nosocomial LRTI, data are insufficient to recommend initiating therapy based on a single PCT level or even repeated measurements. For children with suspected bacterial meningitis, we recommend using a decision rule as an aid to therapeutic decisions, such as the Bacterial Meningitis Score or the Meningitest®; a single PCT level ≥0.5 ng/mL also may be used, but false-negatives may occur. In adults with suspected bacterial meningitis, we suggest integrating serum PCT measurements in a clinical decision rule to help distinguish between viral and bacterial meningitis, using a 0.5 ng/mL threshold. For ICU patients suspected of community-acquired infection, we do not recommend using a threshold serum PCT value to help the decision to initiate antibiotic therapy; data are insufficient to recommend using PCT serum kinetics for the decision to initiate antibiotic therapy in patients suspected of ICU-acquired infection. In children, CRP can probably be used to help discontinue therapy, although the evidence is limited. In adults, antibiotic discontinuation can be based on an algorithm using repeated PCT measurements. In non-immunocompromised out- or in- patients treated for RTI, antibiotics can be discontinued if the PCT level at day 3 is < 0.25 ng/mL or has decreased by >80-90%, whether or not microbiological documentation has been obtained. For ICU patients who have nonbacteremic sepsis from a known site of infection, antibiotics can be stopped if the PCT level at day 3 is < 0.5 ng/mL or has decreased by >80% relative to the highest level recorded, irrespective of the severity of the infectious episode; in bacteremic patients, a minimal duration of therapy of 5 days is recommended.

Adalimumab combined with ciprofloxacin is superior to adalimumab monotherapy in perianal fistula closure in Crohn's disease: a randomised, double-blind, placebo controlled trial (ADAFI)

ObjectiveTo assess whether a combination of adalimumab and ciprofloxacin is superior to adalimumab alone in the treatment of perianal fistulising Crohn's disease (CD).DesignRandomised, double-blind, placebo controlled trial in eight Dutch...

Successful Antibiotic Treatment of Mycobacterium abscessus Pulmonary Disease in an Immunocompetent Individual

The number of subjects with Mycobacterium abscessus lung disease is increasing. The optimal treatment to prevent clinical relapse in these patients has not been well established. At times, antibiotic regimens have also been shown to produce long-term sputum conversion. We describe a case of M. abscessus lung disease in an immunocompetent individual with successful outcome at 24 months, following antibiotic therapy. Initially, an empirical treatment was started intravenously with amikacin (700 mg once-daily), cefoxitin (4 g every 8 h), and oral clarithromycin (500 mg twice daily). Although, the symptoms resolved rapidly, the anti-mycobacterial drugs were discontinued three weeks later, following the onset of hepatotoxicity. Two weeks after discontinuation of therapy, the liver enzymes were returned to normal levels, and amikacin and clarithromycin were reintroduced and continued for another 8 months, when the individual developed hearing loss, which led to further discontinuation of antibiotic therapy. During the subsequent 24 months, broncoscopy, sputum AFB examination and mycobacterial culture were negative. Our management suggests that prompt, individualized and protracted treatment can be curative, in case of mild disease.

Role of procalcitonin in guiding antibiotic therapy

The role of procalcitonin in guiding antibiotic therapy is reviewed. Procalcitonin is a prohormone for calcitonin, which is secreted by the parafollicular cells of the thyroid gland. The biological activity of procalcitonin is significantly different from calcitonin and is believed to be part of the complex inflammatory cascade of the immune system. Procalcitonin has been shown to be elevated in bacterial infections but not in viral infections or other inflammatory conditions. The first published study that suggested that procalcitonin levels increased in the presence of bacterial infection was conducted in France in the early 1990s. Numerous studies have been conducted using procalcitonin-guided therapy to reduce antibiotic use. These studies were performed in one of three clinical settings: outpatient primary care (two multicenter, noninferiority studies of patients with upper- and lower-respiratory-tract infections), emergency room and inpatient (five studies in patients with chronic obstructive pulmonary disease, exacerbation, bronchitis, or community-acquired pneumonia), and the intensive care unit (ICU) (two studies in medical ICU patients and two in postoperative ICU patients with infection or sepsis). Based on the findings of these studies, a cutoff value of 0.25 μg/L in non-ICU patients or of 0.5 μg/L in ICU patients seems appropriate for making a decision about the initiation and discontinuation of antibiotic therapy. In patients with a significantly elevated baseline procalcitonin level, a subsequent drop of >80% appears to be reasonable for discontinuing antibiotics. Published evidence supports the use of procalcitonin as a biomarker of bacterial infection that can be used to reduce antibiotic exposure.

Meningitis aséptica en la población adulta. Etiología y utilidad de las técnicas moleculares en el manejo clínico del paciente

This study describes the epidemiological, clinical and microbiological features of acute aseptic meningitis (AAM) in an adult population, and evaluates the impact of microbiological results on the clinical management of patients. Cases of AAM were prospectively collected between 2007 and 2010 among immunocompetent patients over 14 years-old. Enteroviruses and herpes viruses were determined using nucleic acids detection in CSF. Demographic and clinical data were retrospectively collected from medical records. A total of 94 patients were included, of whom 84 were diagnosed with viral meningitis (VM). The annual incidence of VM ranged from 2.4 to 15.3 cases per 100,000 inhabitants. An aetiological diagnosis was obtained in 76.2% of the patients with VM, 55 enterovirus, 4 HSV-2, 3 VZV, one HSV-1, and one EBV. Forty five per cent of patients were admitted to hospital and 65.8% of them received antibiotic treatment. A positive result prompted immediate discharge of 80% of inpatients and discontinuation of antibiotic therapy in 94.1% of them. The median duration of admission to hospital in these patients was 2.8±2.9 days. Patients without available results during admission completed the antibiotic treatment, and the median hospital stay was 11.6±4.6 days. The annual incidence of AAM is variable. Enteroviruses were the main aetiological agent. Molecular tests revealed the aetiology in 76.2% of cases. Almost half of the patients required hospitalisation, and in these cases a positive result can lead to the immediate discharge of patients, and the diagnostic and therapeutic interventions can be reduced.

Evaluation of doripenem utilization and susceptibilities at a large urban hospital

Bacterial resistance presents a constant challenge in the treatment of hospitalized patients, particularly with Gram-negative infections. Carbapenems have an important role in the treatment of resistant nosocomial organisms. Doripenem, a recently approved carbapenem, has shown efficacy in clinical trials, but there is little published data on utilization in a general patient population. The clinical utilization of doripenem in a general adult inpatient population was evaluated during a carbapenem formulary conversion. A 706-bed acute care tertiary hospital serving an urban community. After formulary conversion to doripenem, the first 100 patients to receive doripenem were included in the analysis. Baseline characteristics were recorded for each patient, along with indication for treatment, prescribing physician, dose and frequency of doripenem and duration of treatment. Patients were monitored for adverse reactions to doripenem. Bacterial culture results were recorded. For positive cultures, doripenem susceptibility was determined by Etest. Patients were followed until discontinuation of antibiotic therapy, discharge or death to determine treatment outcomes. Successful treatment was defined as clinical or microbiological cure, while patients with infection-related mortality or requiring subsequent antibiotics for the index infection were considered treatment failure. Clinical utilization of doripenem, including indications and doses used. Doripenem treatment was recorded in 102 patients. The most common indications for treatment were pneumonia and sepsis. The majority of doripenem orders were written by Infectious Disease or Pulmonology Services. Forty-nine patients were treated successfully with doripenem and six patients experienced treatment failure. The remainder of patients were not evaluable by predefined outcomes criteria. Adverse events were reported in eight patients and included acute renal failure, Clostridium difficile-associated diarrhea and seizures. Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa were the most common organisms in culture results. Doripenem demonstrated in vitro activity against 81% of all organisms and susceptibility results had >90% correlation with meropenem and imipenem susceptibilities. In our limited sample size, doripenem was safe and effective against various types of infections in a general inpatient population with similar bacterial susceptibilities to other cabapenems. Doripenem was utilized for appropriate indications, but doses were frequently outside the manufacturers labeling. Adverse events were uncommon, and no serious adverse events were directly associated with doripenem treatment.