Total Antibiotic Exposure Research Articles

Duration from start of antibiotic exposure to onset of Clostridioides difficile infection for different antibiotics in a non-outbreak setting

Background Antibiotic treatment is a well-known risk factor for Clostridioides difficile infection (CDI). The time from start of antibiotic exposure to onset of CDI for different antibiotics is sparsely studied. CDI with onset in the community is often treatable without in-hospital care while CDI patients treated in hospital need isolation, resulting in higher costs and infection control measures. Objectives To determine the time from start of antibiotic exposure to onset of healthcare facility-associated CDI for different antibiotics. Methods Time between antibiotic exposure and disease onset was evaluated retrospectively with chart reading in a two-centre Swedish setting. A case was attributed to an antibiotic group if this represented more than 2/3 of total antibiotic exposure 30 days before onset of CDI. Results Cephalosporins caused CDI faster (mean 7.6 days), and more often during ongoing antibiotic therapy (81% of the cases) than any other antibiotic group. All other common agents had between 2–3 times longer period between start of exposure to onset of CDI (quinolones more than 3 times). Conclusions The time gap between antibiotic exposure and onset of CDI is markedly different between different antibiotics. Decreased cephalosporin use could delay onset of healthcare facility-associated CDI and limit infections with onset within the hospital. This might decrease costs for inpatient care, need of infection control measures and shortage of beds in the hospital.

The Management of Recurrent Urinary Tract Infection: Non-Antibiotic Bundle Treatment.

Recurrent urinary tract infections (rUTIs) are a common condition with high morbidity and negatively impact the quality of life. They account for approximately 25% of all antibiotic prescriptions and are a public health concern in an era of increasing multidrug-resistant organisms (MDROs). Several non-antibiotic treatment strategies have been tried to curb antimicrobial use, and many are effective to some degree, but no experience testing multimodal interventions. We created a "care bundle" consisting of behavioral interventions, vaginal and oral probiotics, D-mannose, and cranberry to be followed for six months. We enrolled women with rUTIs over three years. Changes in urinary tract infections, antibiotic use, chronic symptoms, and quality of life were compared in the six months before and after participation in the study. Forty-seven women were enrolled in the study, six of whom were excluded from the final analysis. We observed a 76% reduction in urinary tract infections (p < 0.001) and a reduction in total antibiotic exposure of more than 90% (p < 0.001); all chronic symptoms showed a trend toward reduction. Adherence to the bundle was high (87.2%). Overall, 80.5% of women experienced an improvement in their quality of life. In our experience, a bundle protocol is effective in reducing recurrences and antimicrobial use in a cohort of women with rUTIs and results in a subjective improvement in chronic symptoms and quality of life. Further research with larger sample size is needed to confirm these findings.

Safety and Efficacy of Antibiotic De-escalation and Discontinuation in High-Risk Hematological Patients With Febrile Neutropenia: A Single-Center Experience.

BackgroundThere is currently no consensus on optimal duration of antibiotic treatment in febrile neutropenia. We report on the clinical impact of implementation of antibiotic de-escalation and discontinuation strategies based on the Fourth European Conference on Infections in Leukaemia (ECIL-4) recommendations in high-risk hematological patients.MethodsWe studied 446 admissions after introduction of an ECIL-4–based protocol (hereafter “ECIL-4 group”) in comparison to a historic cohort of 512 admissions. Primary clinical endpoints were the incidence of infectious complications including septic shock, infection-related intensive care unit (ICU) admission, and overall mortality. Secondary endpoints included the incidence of recurrent fever, bacteremia, and antibiotic consumption.ResultsBacteremia occurred more frequently in the ECIL-4 group (46.9% [209/446] vs 30.5% [156/512]; P < .001), without an associated increase in septic shock (4.7% [21/446] vs 4.5% [23/512]; P = .878) or infection-related ICU admission (4.9% [22/446] vs 4.1% [21/512]; P = .424). Overall mortality was significantly lower in the ECIL-4 group (0.7% [3/446] vs 2.7% [14/512]; P = .016), resulting mainly from a decrease in infection-related mortality (0.4% [2/446] vs 1.8% [9/512]; P = .058). Antibiotic consumption was significantly reduced by a median of 2 days on antibiotic therapy (12 vs 14; P = .001) and 7 daily antibiotic doses (17 vs 24; P < .001) per admission period.ConclusionsOur results support implementation of ECIL-4 recommendations to be both safe and effective based on real-world data in a large high-risk patient population. We found no increase in infectious complications and total antibiotic exposure was significantly reduced.

A Review on Antimicrobial Stewardship Programs in Multiple Care Settings

Antimicrobial resistance is a global problem that is regarded as one of the most important threats to human health. Misuse of antibiotics leads to an increase in antibiotic resistance as well as higher healthcare costs. Antimicrobial stewardship is a coordinated, multidisciplinary program aimed at improving antimicrobial prescribing to enhance treatment outcomes while reducing unpredictable consequences of antimicrobial use, such as toxicity, pathogenic organism selection, and resistance emergence. Each hospital has its own antimicrobial stewardship program, which requires the enthusiastic participation of both administration and medical staff. The key components are audits and feedbacks, antibiotic pre-authorization, the use of guidelines or written material, and healthcare professional education. These strategies allow for a reduction in total antibiotic exposure while still providing the best care and avoiding the overuse of broad-spectrum antibiotics. Prospective audits can reveal ineffective interventions and suggest changes. The goal of this review is to gain a better understanding of Antimicrobial Stewardship programs so that antibiotic prescribing, dispensing, and administration can be improved in multiple care settings.

Prescribing of long-term antibiotics to adolescents in primary care: a retrospective cohort study.

BackgroundAntibiotic overuse is linked to increased risk of antimicrobial resistance. Long-term antibiotics are commonly used for treating acne and prophylaxis of urinary tract infection. Their contribution to the overall burden of antibiotic use is relatively unknown.AimTo describe the volume of commonly prescribed long-term (≥28 days) antibiotic prescriptions in adolescents and young adults, trends over time, and comparisons with acute prescriptions.Design and settingA retrospective cohort study using UK electronic primary care records.MethodPatients born between 1979 and 1996 and with data in the Care and Health Information Analytics database were included. The main outcome measures were antibiotic prescription rates per 1000 person-years and antibiotic prescription days per person-year between the ages of 11 and 21.ResultsIn total, 320 722 participants received 710 803 antibiotic prescriptions between the ages of 11 and 21 years from 1998 to 2017. Of these 710 803 prescriptions, 191 443 (26.93%) were for long-term antibiotics (≥28 days and ≤6 months in duration). Long-term antibiotics accounted for more than two-thirds (72.48%) of total antibiotic exposure (days per person-year). Total long-term antibiotic prescribing peaked in 2013 at just under 6 days per person-year and declined to around 4 days in 2017.ConclusionAmong adolescents and young adults, exposure to long-term antibiotics (primarily lymecycline used for acne) was much greater than for acute antibiotics and is likely to make an important contribution to antimicrobial resistance. Urgent action is needed to reduce unnecessary exposure to long-term antibiotics in this group. Increasing the use of, and adherence to, effective non-antibiotic treatments for acne is key to achieving this.

Management of Pediatric Nonpathogenic Blood Cultures After Introduction of PCR Technology.

The rapid identification of organisms reported in positive blood cultures via polymerase chain reaction (PCR) can accurately identify a nonpathogenic bacterium and decrease time to definitive identification, as compared with traditional microbiologic methods. How this technology effects clinical and antimicrobial management in children with nonpathogenic bacteria identified in a blood culture without decision support has not been evaluated. A retrospective study of the management of children with positive blood culture results for nonpathogenic organisms before and after implementation of PCR technology. Each cohort's antibiotic management, frequency of repeat cultures, and return visits to an emergency department (ED) were compared. A total 136 patients during this time (49% [n = 67] pre-PCR and 51% [n = 69] post-PCR) had a blood culture positive for nonpathogenic bacterium. Admitted patients had a second specimen sent for testing on fewer occasions (P = .04); however, total antibiotic exposure did not differ significantly (P = .3) after introduction of PCR technology. There was no significant difference in length of stay postintervention (P = .12). Patients discharged directly from the ED had fewer return visits (P = .02) and received fewer repeat blood cultures (P = .04), and antibiotics were administered on fewer occasions after return (P = .04) postintroduction of PCR technology. With the addition of PCR technology, patients with blood cultures positive for nonpathogenic bacteria received less antibiotics, fewer repeat blood cultures, and fewer repeat ED evaluations.

Vancomycin-lock therapy for prevention of catheter-related bloodstream infection in very low body weight infants

BackgroundThis study was to evaluate the effectiveness and safety of vancomycin- lock therapy for the prevention of catheter-related bloodstream infection (CRBSI) in very low body weight (VLBW) preterm infant patients.MethodsOne hundred and thirty-seven cases of VLBW preterm infants who retained peripherally inserted central catheters (PICCs) were retrospectively reviewed, including 68 treating with heparin plus vancomycin (vancomycin-lock group) and 69 with heparin only (control group). The incidence of CRBSI, related pathogenic bacteria, adverse events during the treatment, complications, antibiotic exposure, PICC usage time, hospital stay, etc. were compared between the above two groups.ResultsThe incidence rate of CRBSI in the vancomycin-lock group (4.4%, 3/68) was significantly less than in the control group (21.7%, 15/69, p = 0.004). Total antibiotic exposure time during the whole observation period was significantly shorter in the group than in the control group (11.2 ± 10.0 vs 23.6 ± 16.1 d; p < 0.001). No hypoglycemia occurred during the locking, and the blood concentrations of vancomycin were not detectable.ConclusionsVancomycin-lock may effectively prevent CRBSI in Chinese VLBW preterm infants and reduce the exposure time of antibiotics, without causing obvious side complications.

Autologous Transplant Recipients Have a Healthier Gut Microbiota at Baseline and Faster Recovery from Microbiome Injury Compared to Allogeneic Transplant Recipients

Introduction: Hematopoietic stem cell transplantation (HSCT) is associated with severe intestinal microbiota injury as a consequence of broad spectrum antibiotics, mucosal damage from conditioning, and dietary changes. Intestinal dysbiosis has been correlated with adverse outcomes post-transplant. We aimed to characterize and compare the patterns of microbiota injury that occur post autologous and allogeneic transplant. We characterized the specific risk factors associated with decreased microbial diversity in HSCT, and defined specific bacterial taxa that are enriched or depleted in patients based on the type of transplant and various other risk factors Methods: Stool samples from 35 patients (pts) undergoing HSCT were collected immediately pre-conditioning, at day 14, 28, and 100 post-transplant. 17 pts underwent an autologous (auto-) and 18 pts underwent an allogeneic transplant (allo-HSCT). The stool microbiome was characterized by sequencing of the V3V4 16s rRNA region; a- and b-diversity were determined and differential abundance analysis of OTUs was performed using DESeq2. Results: In the auto-HSCT cohort 70% of pts had plasma cell dyscrasia, and 24% had non-Hodgkin lymphoma. 83% of pts in the allo-HSCT cohort had a myeloid neoplasm, and 17% had a T cell neoplasm. 33% of pts undergoing allo-HSCT developed grade 2-4 GVHD within 100 days and 56% developed GVHD within 6 months. The pre-transplant intestinal microbiome α-diversity was significantly higher in pts undergoing auto-HSCT compared to allo-HSCT (Fig 1). The etiology for this was likely multifactorial. More pts in the allo-HSCT cohort had received antibiotics within 30 days prior to transplant, compared to the auto-HSCT cohort (56% vs 18%). Pts in the allo-HSCT cohort had a higher proportion of VRE or MDR Gram-negative bacteria on screening cultures (44% vs 29%), which may be associated with domination of certain species. In both the allo- and auto-HSCT cohorts, the α-diversity significantly decreased at days 14 and 28, but recovered to pre-transplant levels by day 100. Pts in the auto-HSCT cohort displayed faster recovery kinetics, and had a significantly higher α-diversity at day 28 compared to the allo-HSCT cohort (Fig 1). The microbiome recovery in the auto-HSCT cohort was consistent across the whole group and was characterized by a much smaller variance compared to the allo-HSCT cohort. This may reflect lower total antibiotic exposure in the auto-HSCT cohort (Fig 2). Other factors specific to the allo-HSCT cohort were the occurrence of GVHD and the use of TBI, both of which were associated with decrease in α-diversity in our population (Fig 3). Of note, Faecalibacterium prausnitzii was found to have a &gt;20 log reduction in both the auto and allo-HSCT cohorts. It is a commensal gut bacterium, and its depletion has previously been reported in inflammatory bowel disease. There is very limited data on this bacterium in the peri-transplant setting. It has an anti-inflammatory effect on the intestinal microenvironment through production of butyrate, inhibition of NF-kB, upregulation of regulatory T cell production, and release of metabolites that enhance intestinal barrier function (Lopez-Siles et al, ISME 2017). Transplantation of F. prausnitzii has been shown to decrease inflammation in mice models of colitis (Sokol 2009). We then evaluated the association between microbiota injury and GVHD. α-diversity was significantly decreased at day 14 and day 28 in pts who developed GVHD within 100 days. In differential abundance analysis of samples from pts who developed acute GVHD within 6 months, there was a &gt;20 log reduction in the Bifidobacterium, Blautia, and Eubacterium Dolichum. Decrease in Blautia has previously been associated with increased GVHD related mortality. Bifidobacterium and Eubacterium Dolichum have not been reported in association with GVHD in humans before. All three bacterial taxa reported here are involved in production of short chain fatty acids, which may provide a common protective mechanism. In summary, this study showed that pts undergoing autologous transplant have a healthier pre-transplant microbial diversity, and that microbiota injury heals quicker after transplant. We have identified TBI as a risk factor for microbiome injury, which has not been previously studied in the context of HSCT. We also identify previously unreported bacterial taxa whose depletion is strongly associated with GVHD. Disclosures Assal: Incyte corporation: Consultancy, Research Funding; boston biomedical: Consultancy. Uhlemann:Merk: Research Funding; GSK: Research Funding; Allergan: Research Funding. Reshef:Kite, a Gilead Company: Consultancy, Honoraria, Research Funding; Atara: Consultancy, Research Funding; Magenta: Consultancy; Pfizer: Consultancy; Pharmacyclics: Consultancy, Research Funding; Celgene: Research Funding; Incyte: Consultancy, Research Funding; Shire: Research Funding; BMS: Consultancy.

854. Impact of Antimicrobial Stewardship and Rapid Diagnostics in Children with Staphylococcus aureus Bacteremia

BackgroundRapid diagnostic testing (RDT) in combination with antimicrobial stewardship programs (ASPs) has been associated with improved outcomes in adults with Staphylococcus aureus bacteremia (SAB). Data in children are lacking. In January 2017, Atrium Health implemented a pediatric ASP with blood culture RDT. The objective of this study was to determine the impact of those interventions.MethodsThis was a retrospective, multicenter, quasi-experimental study of children ≤18 years with monomicrobial SAB from March 2015 to August 2016 (pre-intervention; PRE) and March 2017 to August 2018 (post-intervention; POST). The primary outcome was time to an optimal antibiotic. Secondary outcomes included time to effective antibiotic, total antibiotic exposure in the first 5 days, duration of bacteremia, infectious diseases (ID) consultation, time to central line removal, hospital and pediatric ICU length of stay (LOS), need for vasopressors or intubation, recurrence of SAB within 90 days, and inpatient mortality.ResultsOf 101 patients with SAB, 32 and 36 met inclusion criteria for the PRE and POST groups, respectively. The median time to optimal antimicrobial therapy decreased by 23 hours (PRE 44.3 hours vs. POST 21.3 hours; P = 0.008). Duration of bacteremia (65h vs. 40.9 hours; P = 0.028) and mortality (12.5% vs. 0%; P = 0.044) was also significantly reduced. Differences in median time to effective therapy (7 hours vs. 5.1 hours; P = 0.74), total antibiotic exposure in the first 5 days (160.4 hours vs. 152 hours; P = 0.4), hospital LOS (9.9 vs. 8.5 days; P = 0.25), and pediatric ICU LOS (7 vs. 4 days; P = 0.11) did not meet statistical significance, but trended downward. The POST group had more patients with ID consultation (78% vs. 89%, P = 0.23) and shorter time to central line removal (68 hours vs. 20 hours; P = 0.037). There was no difference in the need for vasopressors (3 vs. 3 patients; P = 0.99) or intubation (2 vs. 4 patients; P = 0.68). Throughout the study period, recurrence of SAB only occurred in one patient (PRE).ConclusionConcurrent implementation of RDT and an ASP in pediatric patients with SAB decreased time to optimal antimicrobial therapy, duration of bacteremia, and mortality. RDT coupled with timely feedback from an ASP contributed to improved SAB management and clinical outcomes in children.Disclosures All Authors: No reported Disclosures.

Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections.

Acute respiratory infections (ARIs) comprise of a large and heterogeneous group of infections including bacterial, viral, and other aetiologies. In recent years, procalcitonin (PCT), a blood marker for bacterial infections, has emerged as a promising tool to improve decisions about antibiotic therapy (PCT-guided antibiotic therapy). Several randomised controlled trials (RCTs) have demonstrated the feasibility of using procalcitonin for starting and stopping antibiotics in different patient populations with ARIs and different settings ranging from primary care settings to emergency departments, hospital wards, and intensive care units. However, the effect of using procalcitonin on clinical outcomes is unclear. This is an update of a Cochrane review and individual participant data meta-analysis first published in 2012 designed to look at the safety of PCT-guided antibiotic stewardship. The aim of this systematic review based on individual participant data was to assess the safety and efficacy of using procalcitonin for starting or stopping antibiotics over a large range of patients with varying severity of ARIs and from different clinical settings. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), which contains the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE, and Embase, in February 2017, to identify suitable trials. We also searched ClinicalTrials.gov to identify ongoing trials in April 2017. We included RCTs of adult participants with ARIs who received an antibiotic treatment either based on a procalcitonin algorithm (PCT-guided antibiotic stewardship algorithm) or usual care. We excluded trials if they focused exclusively on children or used procalcitonin for a purpose other than to guide initiation and duration of antibiotic treatment. Two teams of review authors independently evaluated the methodology and extracted data from primary studies. The primary endpoints were all-cause mortality and treatment failure at 30 days, for which definitions were harmonised among trials. Secondary endpoints were antibiotic use, antibiotic-related side effects, and length of hospital stay. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using multivariable hierarchical logistic regression adjusted for age, gender, and clinical diagnosis using a fixed-effect model. The different trials were added as random-effects into the model. We conducted sensitivity analyses stratified by clinical setting and type of ARI. We also performed an aggregate data meta-analysis. From 32 eligible RCTs including 18 new trials for this 2017 update, we obtained individual participant data from 26 trials including 6708 participants, which we included in the main individual participant data meta-analysis. We did not obtain individual participant data for four trials, and two trials did not include people with confirmed ARIs. According to GRADE, the quality of the evidence was high for the outcomes mortality and antibiotic exposure, and quality was moderate for the outcomes treatment failure and antibiotic-related side effects.Primary endpoints: there were 286 deaths in 3336 procalcitonin-guided participants (8.6%) compared to 336 in 3372 controls (10.0%), resulting in a significantly lower mortality associated with procalcitonin-guided therapy (adjusted OR 0.83, 95% CI 0.70 to 0.99, P = 0.037). We could not estimate mortality in primary care trials because only one death was reported in a control group participant. Treatment failure was not significantly lower in procalcitonin-guided participants (23.0% versus 24.9% in the control group, adjusted OR 0.90, 95% CI 0.80 to 1.01, P = 0.068). Results were similar among subgroups by clinical setting and type of respiratory infection, with no evidence for effect modification (P for interaction > 0.05). Secondary endpoints: procalcitonin guidance was associated with a 2.4-day reduction in antibiotic exposure (5.7 versus 8.1 days, 95% CI -2.71 to -2.15, P < 0.001) and lower risk of antibiotic-related side effects (16.3% versus 22.1%, adjusted OR 0.68, 95% CI 0.57 to 0.82, P < 0.001). Length of hospital stay and intensive care unit stay were similar in both groups. A sensitivity aggregate-data analysis based on all 32 eligible trials showed similar results. This updated meta-analysis of individual participant data from 12 countries shows that the use of procalcitonin to guide initiation and duration of antibiotic treatment results in lower risks of mortality, lower antibiotic consumption, and lower risk for antibiotic-related side effects. Results were similar for different clinical settings and types of ARIs, thus supporting the use of procalcitonin in the context of antibiotic stewardship in people with ARIs. Future high-quality research is needed to confirm the results in immunosuppressed patients and patients with non-respiratory infections.

Procalcitonin to guide antibiotic administration in COPD exacerbations: a meta-analysis.

Challenges in the differentiation of the aetiology of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) have led to significant overuse of antibiotics. Serum procalcitonin, released in response to bacterial infections, but not viral infections, could possibly identify AECOPD requiring antibiotics. In this meta-analysis we assessed the clinical effectiveness of procalcitonin-based protocols to initiate or discontinue antibiotics in patients presenting with AECOPD.Based on a prospectively registered protocol, we reviewed the literature and selected randomised or quasi-randomised trials comparing procalcitonin-based protocols to initiate or discontinue antibiotics versus standard care in AECOPD. We followed Cochrane and GRADE (Grading of Recommendations, Assessment, Development and Evaluation) guidance to assess risk of bias, quality of evidence and to perform meta-analyses.We included eight trials evaluating 1062 patients with AECOPD. Procalcitonin-based protocols decreased antibiotic prescription (relative risk (RR) 0.56, 95% CI 0.43-0.73) and total antibiotic exposure (mean difference (MD) -3.83, 95% CI (-4.32--3.35)), without affecting clinical outcomes such as rate of treatment failure (RR 0.81, 0.62-1.06), length of hospitalisation (MD -0.76, -1.95-0.43), exacerbation recurrence rate (RR 0.96, 0.69-1.35) or mortality (RR 0.99, 0.58-1.69). However, the quality of the available evidence is low to moderate, because of methodological limitations and small overall study population.Procalcitonin-based protocols appear to be clinically effective; however, confirmatory trials with rigorous methodology are required.

The real life application of a procalcitonin-based algorithm to reduce antibiotic exposure in hospitalized patients with community acquired pneumonia: a proof of concept

Community-acquired pneumonia (CAP) represents a common cause of hospitalization in Internal Medicine wards and a frequent cause of antibiotic prescription. An approach based on procalcitonin (PCT) algorithm, has shown to reduce the antibiotic exposure without affecting outcome, in patients admitted to hospital for pneumonia We conducted a study to evaluate the role of a PCT algorithm in a &lt;em&gt;real-life&lt;/em&gt; perspective, to reduce the length of antibiotic treatment (AT) in patients hospitalized with CAP. We performed a prospective case-control study, enrolling patients with CAP admitted to an Internal Medicine ward of Careggi Hospital, between December 2013 and February 2014. We used a validated algorithm of AT guided by PCT in CAP. Discontinuation of AT was strongly indicated when PCT level was normal or reduced by 80% in patients with PCT values higher than 10 pg/mL on admission. PCT was drawn on admission, 24 h, 4&lt;sup&gt;th&lt;/sup&gt; day and 6&lt;sup&gt;th&lt;/sup&gt; day from admission. The outcomes evaluated were the length of AT, the length of in hospital stay, mortality and serious adverse clinical events. Forty-six patients were consecutively enrolled. On 20 patients, AT was discontinued according to protocol and on 26 patients the AT was continued on clinical judgement. At the baseline, both groups were similar regarding clinical, laboratory, microbiology characteristics, and CURB-65 score. PCT guidance reduced total antibiotic exposure (5.1±1.5 &lt;em&gt;vs&lt;/em&gt; 9.1±5.8 days, P=0.005) without any increase of mortality or serious clinical event. In our study, a PCT algorithm was a useful and safe tool to guide the AT in patients with CAP, reducing the antibiotic exposure.

Effect of Procalcitonin Testing on Health-care Utilization and Costs in Critically Ill Patients in the United States

There is a growing use of procalcitonin (PCT) to facilitate the diagnosis and management of severe sepsis. We investigated the impact of one to two PCT determinations on ICU day 1 on health-care utilization and cost in a large research database. A retrospective, propensity score-matched multivariable analysis was performed on the Premier Healthcare Database for patients admitted to the ICU with one to two PCT evaluations on day 1 of ICU admission vspatients who did not have PCT testing. A total of 33,569 PCT-managed patients were compared with 98,543 propensity score-matched non-PCT patients. In multivariable regression analysis, PCT utilization was associated with significantly decreased total length of stay (11.6days [95%CI, 11.4 to 11.7] vs12.7days [95%CI, 12.6 to 12.8]; 95%CI for difference, 1 to 1.3; P< .001) and ICU length of stay (5.1days [95%CI, 5.1 to 5.2] vs5.3days [95%CI, 5.3 to 5.4]; 95%CI for difference, 0.1 to 0.3; P< .03), and lower hospital costs ($30,454 [95%CI, 29,968 to 31,033] vs$33,213 [95%CI, 32,964 to 33,556); 95%CI for difference, 2,159 to 3,321; P< .001). There was significantly less total antibiotic exposure (16.2days [95%CI, 16.1 to 16.5] vs16.9days [95%CI, 16.8 to 17.1]; 95%CI for difference, -0.9 to 0.4; P= .006) in PCT-managed patients. Patients in the PCT group were more likely to be discharged to home (44.1%[95%CI, 43.7 to 44.6] vs41.3%[95%CI, 41 to 41.6]; 95%CI for difference, 2.3 to 3.3; P= .006). Mortality was not different in an analysis including the 96%of patients who had an independent measure of mortality risk available (19.1%[95%CI, 18.7 to 19.4] vs19.1%[95%CI, 18.9 to 19.3]; 95%CI for difference, -0.5 to 0.4; P= .93). Use of PCT testing on the first day of ICU admission was associated with significantly lower hospital and ICU lengths of stay, as well as decreased total, ICU, and pharmacy cost of care. Further elucidation of clinical outcomes requires additional data.

Duration of Antimicrobial Therapy in Community Acquired Pneumonia: Less Is More

Community acquired pneumonia (CAP) represents the most common cause of infection-related morbidity and mortality worldwide. Appropriate treatment of CAP is challenging and sometimes limited by the availability to obtain rapid and timely identification of the etiologic agent in order to initiate or deescalate the correct antimicrobial therapy. As a consequence, prescribers frequently select empiric antimicrobial therapy using clinical judgment, local patterns of antimicrobial resistance, and, sometimes, individual patient expectations. These issues may contribute to prolonged courses of inappropriate therapy. In this review, we discuss the evidence and recommendations from international guidelines for the management of CAP and the clinical trials that specifically addressed duration of antimicrobial therapy for CAP in adults. In randomized controlled trials comparing the clinical efficacy of a short-course antimicrobial regimen versus an extended-course regimen, no differences in terms of clinical success, bacterial eradication, adverse events, and mortality were observed. The use of biomarkers, such as procalcitonin, to guide the initiation and duration of antimicrobial therapy may reduce total antibiotic exposure and treatment duration, healthcare costs, and the risk of developing antimicrobial resistance. In clinical practice, antimicrobial stewardship interventions may improve the management of CAP and may help in reducing treatment duration. Sometimes “less is more” in CAP.

Procalcitonin‐guided antibiotic therapy: A systematic review and meta‐analysis

The utility of procalcitonin to manage patients with infections is unclear. A systematic review of comparative studies using procalcitonin-guided antibiotic therapy in patients with infections was performed. Randomized, controlled trials comparing procalcitonin-guided initiation, intensification, or discontinuation of antibiotic therapy to clinically guided therapy were included. Outcomes were antibiotic usage, morbidity, and mortality. MEDLINE, EMBASE, the Cochrane Database, National Institute for Clinical Excellence, the National Guideline Clearinghouse, and the Health Technology Assessment Programme were searched from January 1, 1990 to December 16, 2011. Eighteen randomized, controlled trials were included. Data were pooled into clinically similar patient populations. In adult intensive care unit (ICU) patients, procalcitonin-guided discontinuation of antibiotics reduced antibiotic duration by 2.05 days (95% confidence interval [CI]: -2.59 to -1.52) without increasing morbidity or mortality. In contrast, procalcitonin-guided intensification of antibiotics in adult ICU patients increased antibiotic usage and morbidity. In adult patients with respiratory tract infections, procalcitonin guidance significantly reduced antibiotic duration by 2.35 days (95% CI: -4.38 to -0.33), antibiotic prescription rate by 22% (95% CI: -41% to -4%), and total antibiotic exposure without affecting morbidity or mortality. A single, good quality study of neonates with suspected sepsis demonstrated reduced antibiotic duration by 22.4 hours (P = 0.012) and reduced the proportion of neonates on antibiotics for ≥ 72 hours by 27% (P = 0.002) with procalcitonin guidance. Procalcitonin guidance can safely reduce antibiotic usage when used to discontinue antibiotic therapy in adult ICU patients and when used to initiate or discontinue antibiotics in adult patients with respiratory tract infections.

Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections

Acute respiratory infections (ARIs) comprise a large and heterogeneous group of infections including bacterial, viral and other aetiologies. In recent years, procalcitonin - the prohormone of calcitonin - has emerged as a promising marker for the diagnosis of bacterial infections and for improving decisions about antibiotic therapy. Several randomised controlled trials (RCTs) have demonstrated the feasibility of using procalcitonin for starting and stopping antibiotics in different patient populations with acute respiratory infections and different settings ranging from primary care to emergency departments (EDs), hospital wards and intensive care units (ICUs). The aim of this systematic review based on individual patient data was to assess the safety and efficacy of using procalcitonin for starting or stopping antibiotics over a large range of patients with varying severity of ARIs and from different clinical settings. We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2011, Issue 2) which contains the Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to May 2011) and EMBASE (1974 to May 2011) to identify suitable trials. We included RCTs of adult participants with ARIs who received an antibiotic treatment either based on a procalcitonin algorithm or usual care/guidelines. Trials were excluded if they exclusively focused on paediatric patients or if they used procalcitonin for another purpose than to guide initiation and duration of antibiotic treatment. Two teams of review authors independently evaluated the methodology and extracted data from primary studies. The primary endpoints were all-cause mortality and treatment failure at 30 days. For the primary care setting, treatment failure was defined as death, hospitalisation, ARI-specific complications, recurrent or worsening infection, and patients reporting any symptoms of an ongoing respiratory infection at follow-up. For the ED setting, treatment failure was defined as death, ICU admission, re-hospitalisation after index hospital discharge, ARI-associated complications, and recurrent or worsening infection within 30 days of follow-up. For the ICU setting, treatment failure was defined as death within 30 days of follow-up. Secondary endpoints were antibiotic use (initiation of antibiotics, duration of antibiotics and total exposure to antibiotics (total amount of antibiotic days divided by total number of patients)), length of hospital stay for hospitalised patients, length of ICU stay for critically ill patients, and number of days with restricted activities within 14 days after randomisation for primary care patients. For the two co-primary endpoints of all-cause mortality and treatment failure, we calculated odds ratios (ORs) and 95% confidence intervals (CIs) using multivariable hierarchical logistic regression. The hierarchical regression model was adjusted for age and clinical diagnosis as fixed-effect. The different trials were added as random-effects into the model. We fitted corresponding linear regression models for antibiotic use. We conducted sensitivity analyses stratified by clinical setting and ARI diagnosis to assess the consistency of our results. We included 14 trials with 4221 participants. There were 118 deaths in 2085 patients (5.7%) assigned to procalcitonin groups compared to 134 deaths in 2126 control patients (6.3%) (adjusted OR 0.94, 95% CI 0.71 to 1.23). Treatment failure occurred in 398 procalcitonin group patients (19.1%) and in 466 control patients (21.9%). Procalcitonin guidance was not associated with increased mortality or treatment failure in any clinical setting, or ARI diagnosis. These results proved robust in various sensitivity analyses. Total antibiotic exposure was significantly reduced overall (median (interquartile range) from 8 (5 to 12) to 4 (0 to 8) days; adjusted difference in days, -3.47, 95% CI -3.78 to -3.17, and across all the different clinical settings and diagnoses. Use of procalcitonin to guide initiation and duration of antibiotic treatment in patients with ARI was not associated with higher mortality rates or treatment failure. Antibiotic consumption was significantly reduced across different clinical settings and ARI diagnoses. Further high-quality research is needed to confirm the safety of this approach for non-European countries and patients in intensive care. Moreover, future studies should also establish cost-effectiveness by considering country-specific costs of procalcitonin measurement and potential savings in consumption of antibiotics and other healthcare resources, as well as secondary cost savings due to lower risk of side effects and reduced antimicrobial resistance.

Antimicrobial Stewardship Pharmacist Interventions for Coagulase-Negative Staphylococci Positive Blood Cultures Using Rapid Polymerase Chain Reaction

No studies exist regarding the value of pharmacist interventions using rapid identification of coagulase-negative staphylococci (CoNS) by rapid polymerase chain reaction (rPCR) from blood cultures. To evaluate the impact of interventions by infectious diseases pharmacists (ID PharmDs) on blood cultures positive for CoNS using rPCR and assess the duration of antistaphylococcal antibiotic therapy, hospital length of stay (LOS), and related costs. A quasi-experimental, pre- and postintervention study of patients with positive blood cultures for CoNS, identified using rPCR, was conducted. Patients were included if there was a blood culture for CoNS from January 1, 2011, to March 31, 2011 (preintervention), or October 1, 2011, to January 18, 2012 (postintervention). Exclusion criteria included age younger than 18 years or 89 years or older, neutropenia, incomplete records, and duplicate or mixed blood cultures. The setting was a 1200-bed academic medical center. The ID PharmD intervened on blood cultures identified in the postintervention group as CoNS after notification from the microbiology laboratory. The pre- and postintervention groups were compared to analyze the effect of the intervention. The primary outcome was time to discontinuation of antistaphylococcal antibiotics by the pharmacist intervention in patients with a positive blood culture for CoNS that was determined to be a contaminant. We analyzed 53 patients (31 preintervention, 22 postintervention) with CoNS blood culture contaminants. In the postintervention group, antistaphylococcal antibiotics were discontinued 32.0 hours sooner from time of rPCR result (median 57.7 vs 25.7 hours; p = 0.005), total antibiotic exposure decreased 43.5 hours (97.6 vs 54.1 hours; p = 0.011), infection-related LOS decreased 4.5 days (10 vs 5.5 days; p = 0.018), and infection-related costs decreased $8338 ($28,973 vs $20,635; p = 0.144). The pharmacist initiated vancomycin in 7 (21.9%) patients with CoNS bloodstream infections. Timely interventions by ID PharmDs using rPCR are required to impact the outcomes of patients with positive blood cultures for CoNS.

Antibiotic lock solutions allow less systemic antibiotic exposure and less catheter malfunction without adversely affecting antimicrobial resistance patterns

There are current concerns that antibiotic lock solutions (ABL) can induce antimicrobial resistance in long-term hemodialysis patients. Retrospective chart review of 157 children on hemodialysis between January 1997 and June 2006 was performed. In ERA I, only systemic antibiotics were used. In ERA II, ABL were added to systemic antibiotics when needed. In ERA III, ABL were used for treatment of all cases of catheter-related bacteremia (CRB) and for CRB prophylaxis in high-risk patients. The study includes 111,325 catheter days. The CRB incidence was 3.9 CRB/1000 catheter days. There was significant decrease for the total systemic antibiotic exposure (P = 0.0484) and the percentage of catheters lost to malfunction (P = 0.001) in ERA III. Protocol ABL exposure was associated with a trend to increased tobramycin-gentamicin resistance for gram-positive CRBs (P = 0.2586) but with improved tobramycin-gentamicin resistance for gram-negative (P = 0.0949) and polymicrobial CRBs (P = 0.1776) and improved vancomycin resistance for gram-positive CRBs (P = 0.0985). This retrospective analysis does not support the premise that ABL use will promote antimicrobial resistance in the hemodialysis population. The decreased exposure to systemic antibiotics by vigorous ABL use may even improve the antimicrobial resistance patterns in this population in the long term.

Procalcitonin to guide initiation and duration of antibiotic treatment in acute respiratory infections: an individual patient data meta-analysis.

Procalcitonin algorithms may reduce antibiotic use for acute respiratory tract infections (ARIs). We undertook an individual patient data meta-analysis to assess safety of this approach in different ARI diagnoses and different clinical settings. We identified clinical trials in which patients with ARI were assigned to receive antibiotics based on a procalcitonin algorithm or usual care by searching the Cochrane Register, MEDLINE, and EMBASE. Individual patient data from 4221 adults with ARIs in 14 trials were verified and reanalyzed to assess risk of mortality and treatment failure-overall and within different clinical settings and types of ARIs. Overall, there were 118 deaths in 2085 patients (5.7%) assigned to procalcitonin groups compared with 134 deaths in 2126 control patients (6.3%; adjusted odds ratio, 0.94; 95% confidence interval CI, .71-1.23)]. Treatment failure occurred in 398 procalcitonin group patients (19.1%) and in 466 control patients (21.9%; adjusted odds ratio, 0.82; 95% CI, .71-.97). Procalcitonin guidance was not associated with increased mortality or treatment failure in any clinical setting or ARI diagnosis. Total antibiotic exposure per patient was significantly reduced overall (median [interquartile range], from 8 [5-12] to 4 [0-8] days; adjusted difference in days, -3.47 [95% CI, -3.78 to -3.17]) and across all clinical settings and ARI diagnoses. Use of procalcitonin to guide initiation and duration of antibiotic treatment in patients with ARIs was effective in reducing antibiotic exposure across settings without an increase in the risk of mortality or treatment failure. Further high-quality trials are needed in critical-care patients.

Year in review 2011: Respiratory infections, tuberculosis, pleural diseases, bronchoscopic intervention and imaging

This review highlights important contributions published in Respirology and other reputable respiratory journals in 2011 in four principle respiratory medicine areas, namely pulmonary infections, tuberculosis (TB), pleural diseases and chest imaging/interventional pulmonology. The articles have been selected for their insight, reliability and potential impact on clinical practice. From a total of 111 original articles and 40 review papers published in Respirology that year, 34% and 40%, respectively, were devoted to the earlier topics.