Optimal Duration Of Antibiotic Treatment Research Articles

The optimal antibiotic treatment duration for community-acquired pneumonia in adults diagnosed in general practice in Denmark (CAP-D): an open-label, pragmatic, randomised controlled trial

BackgroundUse of antibiotics is the main driver of antimicrobial resistance which is considered one of the biggest threats to human health. In Denmark, most antibiotics are prescribed in general practice. Acute lower respiratory tract infections, including community-acquired pneumonia (CAP), are among the most frequent indications for antibiotic prescribing. Phenoxymethylpenicillin is established as first-line treatment in general practice in Denmark. However, the treatment duration with phenoxymethylpenicillin is mostly based on traditions. Both 5 and 7 days of treatment is recommended in Danish guidelines, and when asking the general practitioners about what treatment duration, they prescribe the variation is even bigger. Several hospital-based studies have proven short course (≤ 6 days) antibiotic treatment non-inferior to long course (≥ 7 days) treatment of CAP. No evidence exists on the optimal treatment duration for CAP in non-hospitalised patients.This randomised controlled trial aim to investigate the optimal treatment duration with phenoxymethylpenicillin for CAP in adults diagnosed in general practice in Denmark.MethodsThis is an open-label, pragmatic, randomised controlled, five-arm DURATIONS trial. Participants will be recruited from at least 24 general practices in Denmark. Eligible participants are adults, with no pre-existing lung disease, presenting with symptoms of CAP, and in whom the general practitioner finds it relevant to treat with antibiotics. The study will compare treatment with phenoxymethylpenicillin 1.2 MIE q.i.d. in 3, 4, 5, 6, and 7 days.DiscussionThis study will provide evidence for the optimal antibiotic treatment duration of CAP in general practice and inform future guidelines on CAP in all countries using phenoxymethylpenicillin for the treatment of acute respiratory tract infections in adults. The results of this study might also be used to guide treatment recommendations in other countries using phenoxymethylpenicillin.Moreover, a (potential) reduction in antibiotic use might lower the development of antimicrobial resistance, increase patient treatment adherence, reduce risks of adverse events, and lower the economical expTrial registrationClinicalTrials.gov: NCT06295120. Registered 28 February 2024. The Scientific Ethics Committee for the North Denmark Region: N-20230039.

Shorter versus longer-course of antibiotic therapy for urinary tract infections in pediatric population: an updated meta-analysis.

Urinary tract infections (UTI) affect between 3% to 7.5% of the febrile pediatric population each year, being one of the most common bacterial infections in pediatrics. Nevertheless, there is no consensus in the medical literature regarding the duration of per oral (p.o.) antibiotic therapy for UTI among these patients. Therefore, our meta-analysis aims to assess the most effective therapy length in this scenario. PubMed, Cochrane, and Embase were searched for randomized controlled trials (RCTs) comparing short (≤ 5days) with long-course (≥ 7days) per os (p.o.) antibiotic therapy for children with UTI. Statistical analysis was performed using R Studio version 4.2.1, heterogeneity was assessed with I2 statistics, and the risk of bias was evaluated using the RoB-2 tool. Risk Ratios (RR) with p < 0.05 were considered statistically significant. Seventeen studies involving 1666 pediatric patients were included. Of these, 890 patients (53.4%) were randomized to receive short-course therapy. Patients undergoing short-course therapy showed higher treatment failure rates (RR 1.61; 95% CI 1.15-2.27; p = 0.006). Furthermore, there were no statistically significant differences between groups regarding reinfection (RR 0.73; 95% CI 0.47-1.13; p = 0156) and relapse rates (RR 1.47; 95% CI 0.8-2.71; p = 0.270). Conclusion: In summary, our results suggest that long-course p.o. antibiotic therapy is associated with a lower rate of treatment failure when compared to short-course p.o. antibiotic therapy. There was no statistical difference between both courses regarding reinfection and relapse rates within 15months. PROSPERO identifier: CRD42023456745. What is Known: • Urinary tract infections (UTIs) are common in children, affecting around 7.5% of those under 18. • The optimal duration of antibiotic treatment for pediatric UTIs has been a subject of debate. What is New: • Short-course therapy (5 or fewer days) was associated with a significantly higher failure rate when compared to long-course therapy. • There was no significant difference in reinfection and relapse rates within 15months between short and long-course therapy.

Machine learning-derived blood culture classification with both predictive and prognostic values in the intensive care unit: A retrospective cohort study

ObjectivesDiagnosis and management of intensive care unit (ICU)-acquired bloodstream infections are often based on positive blood culture results. This retrospective cohort study aimed to develop a classification model using data-driven characterisation to optimise the management of intensive care patients with blood cultures. Setting, methodology/designAn unsupervised clustering model was developed based on the clinical characteristics of patients with blood cultures in the Medical Information Mart for Intensive Care (MIMIC)-IV database (n = 2451). It was tested using the data from the MIMIC-III database (n = 2047). Main outcome measuresThe prognosis, blood culture outcomes, antimicrobial interventions, and trajectories of infection indicators were compared between clusters. ResultsFour clusters were identified using machine learning-based k-means clustering based on data obtained 48 h before the first blood culture sampling. Cluster γ was associated with the highest 28-day mortality rate, followed by clusters α, δ, and β. Cluster γ had a higher fungal isolation rate than cluster β (P < 0.05). Cluster δ was associated with a higher isolation rate of Gram-negative organisms and fungi (P < 0.05). Patients in clusters γ and δ underwent more femoral site vein catheter placements than those in cluster β (P < 0.001, all). Patients with a duration of antibiotics treatment of 4, 6, and 7 days in clusters α, δ, and γ, respectively, had the lowest 28-day mortality rate. ConclusionsMachine learning identified four clusters of intensive care patients with blood cultures, which yielded different prognoses, blood culture outcomes, and optimal duration of antibiotic treatment. Such data-driven blood culture classifications suggest further investigation should be undertaken to optimise treatment and improve care. Implications for clinical practiceIntensive care unit-acquired bloodstream infections are heterogeneous. Meaningful classifications associated with outcomes should be described. Using machine learning and cluster analysis could help in understanding heterogeneity. Data-driven blood culture classification could identify distinct physiological states and prognoses before deciding on blood culture sampling, optimise treatment, and improve care.

Shorter Versus Longer-term Antibiotic Treatments for Community-Acquired Pneumonia in Children: A Meta-analysis.

The optimal duration of antibiotic treatment of children with community-acquired pneumonia (CAP) remains unclear. This study aimed to compare the efficacy and safety of shorter versus longer duration of antibiotic treatment of children with CAP. We searched Medline, Embase, CENTRAL, and CINAHL. Randomized clinical trials comparing shorter (≤5 days) with longer duration antibiotic treatments in children with CAP. Paired reviewers independently extracted data and we performed random-effects meta-analyses to summarize the evidence. Sixteen trials with 12 774 patients, treated as outpatients with oral antibiotics, proved eligible. There are probably no substantial differences between shorter-duration and longer-duration antibiotics in clinical cure (odds ratio 1.01, 95% confidence interval [CI] 0.87 to 1.17; risk difference [RD] 0.1%; moderate certainty), treatment failure (relative risk [RR] 1.06, 95% CI 0.93 to 1.21; RD 0.3%; moderate certainty), and relapse (RR 1.12, 95% CI 0.92 to 1.35; RD 0.5%; moderate certainty). Compared with longer-duration antibiotics, shorter-duration antibiotics do not appreciably increase mortality (RD 0.0%, 95% CI -0.2 to 0.1; high certainty), and probably have little or no impact on the need for change in antibiotics (RR 1.03, 95% CI 0.72 to 1.47; RD 0.2%; moderate certainty), need for hospitalization (RD -0.2%, 95% CI -0.9 to 0.5; moderate certainty), and severe adverse events (RD 0.0%, 95% CI -0.2 to 0.2; moderate certainty). For some outcomes, evidence was lacking. Duration of antibiotic therapy likely makes no important difference in patient-important outcomes. Healthcare workers should prioritize the use of shorter-duration antibiotics for children with CAP treated as outpatients with oral antibiotics.

Short course antibiotic treatment of Gram-negative bacteraemia (GNB5): a study protocol for a randomised controlled trial

IntroductionProlonged use of antibiotics is closely related to antibiotic-associated infections, antimicrobial resistance and adverse drug events. The optimal duration of antibiotic treatment for Gram-negative bacteremia (GNB) with a urinary tract...

A randomized clinical trial of antibiotic treatment duration in preterm premature rupture of membranes: 7 days versus until delivery.

Antibiotic treatment in preterm premature rupture of membranes (PPROM) can prolong the interval from membrane rupture to delivery and improve neonatal outcomes; however the duration of antibiotic treatment for PPROM has rarely been compared in prospective studies. To investigate the optimal duration of antibiotic treatment for PPROM, we performed a randomized controlled trial comparing neonatal morbidity and infantile neurological outcomes between two groups of PPROM patients who received antibiotic treatment for 7 days or until delivery. This prospective randomized study included patients who were diagnosed with PPROM between 22+0 weeks and 33+6 weeks of gestation. The enrolled patients were randomly assigned to receive intravenous cefazolin (1 g dose every 12 hours) and oral clarithromycin (500 mg dose every 12 hours) for 7 days or until delivery. The study protocol was registered at clinicaltrials.gov (NCT01503606). The primary outcome was neonatal composite morbidity, and the secondary outcome was neurological outcomes at 12 months of corrected age. We enrolled 150 patients and allocated 74 and 76 of them to the 7-day and until-delivery groups, respectively. Analysis was done by per protocol. After excluding cases lost to follow-up or with protocol violations, 63 (7-day regimen) and 61 (until-delivery regimen) PPROM patients and their babies were compared. There was no significant difference in pregnancy outcomes, including gestational age at delivery and interval from rupture of membranes (ROM) to delivery, between the two groups. Among the neonatal outcomes, bronchopulmonary dysplasia, intraventricular hemorrhage, retinopathy of prematurity, necrotizing enterocolitis, and proven neonatal sepsis did not differ between the groups. However, the rate of respiratory distress syndrome (RDS) (32.8% vs. 50.8%, P=.039) and composite neonatal morbidities (34.4% vs. 53.9%, P=.026) were lower in the until-delivery group compared to the 7-day group. This difference remained statistically significant after a multivariable analysis adjusting for maternal age, twin pregnancy, use of antenatal corticosteroids, the ROM to delivery interval, and gestational age at delivery. Infantile neurological outcomes were evaluated in 70% of the enrolled patients and did not differ between the groups. Overall, until-delivery regimen of cefazolin and clarithromycin in PPROM showed lower incidence of composite neonatal morbidities, and of RDS compared to the 7-day regimen and both regimens showed otherwise similar other individual neonatal morbidities and infantile neurological outcomes.

Optimal duration of antibiotic treatment for community-acquired pneumonia in adults: a systematic review and duration-effect meta-analysis

ObjectivesTo find the optimal treatment duration with antibiotics for community-acquired pneumonia (CAP) in adults.DesignSystematic review and duration-effect meta-analysis.Data sourcesMEDLINE, Embase and CENTRAL through 25 August 2021.Eligibility criteriaAll randomised controlled trials...

Six versus 2 weeks treatment with doxycycline in European Lyme neuroborreliosis: a multicentre, non-inferiority, double-blinded, randomised and placebo-controlled trial

BackgroundThere is limited evidence regarding optimal duration of antibiotic treatment in neuroborreliosis. We aimed to compare efficacy and safety of oral doxycycline for 2 and 6 weeks in European Lyme...

Comparison of 8 versus 15days of antibiotic therapy for Pseudomonas aeruginosa ventilator-associated pneumonia in adults: a randomized, controlled, open-label trial.

Duration of antibiotic therapy for ventilator-associated pneumonia (VAP) due to non-fermenting Gram-negative bacilli (NF-GNB), including Pseudomonas aeruginosa (PA) remains uncertain. We aimed to assess the non-inferiority of a short duration of antibiotics (8days) vs. prolonged antibiotic therapy (15days) in VAP due to PA (PA-VAP). We conducted a nationwide, randomized, open-labeled, multicenter, non-inferiority trial to evaluate optimal duration of antibiotic treatment in PA-VAP. Eligible patients were adults with diagnosis of PA-VAP and randomly assigned in 1:1 ratio to receive a short-duration treatment (8days) or a long-duration treatment (15days). A pre-specified analysis was used to assess a composite endpoint combining mortality and PA-VAP recurrence rate during hospitalization in the intensive care unit (ICU) within 90days. The study was stopped after 24 months due to slow inclusion rate. In intention-to-treat population (n = 186), the percentage of patients who reached the composite endpoint was 25.5% (N = 25/98) in the 15-day group versus 35.2% (N = 31/88) in the 8-day group (difference 9.7%, 90% confidence interval (CI) -1.9%-21.2%). The percentage of recurrence of PA-VAP during the ICU stay was 9.2% in the 15-day group versus 17% in the 8-day group. The two groups had similar median days of mechanical ventilation, of ICU stay, number of extra pulmonary infections and acquisition of multidrug-resistant (MDR) pathogens during ICU stay. Our study failed to show the non-inferiority of a short duration of antibiotics in the treatment of PA-VAP, compared to a long duration. The short duration strategy may be associated to an increase of PA-VAP recurrence. However, the lack of power limits the interpretation of this study.

Chronic cholecystitis: Diagnostic and therapeutic insights from formerly bile-farmed Asiatic black bears (Ursus thibetanus).

Across Southeast Asia and China, more than 17000 Asian bears are kept under suboptimal conditions and farmed for their bile to meet the consumer demand for traditional medicine products. Years of unsterile and repetitive bile extraction contribute to the development of chronic sterile or bacterial cholecystitis, a pathology commonly diagnosed in formerly bile-farmed bears. In both human and veterinary medicine, the diagnostic value of the macroscopic bile examination for assessing gallbladder disease is unclear. The objective of this study is to identify the role of gallbladder bile color, viscosity, and turbidity, while comparing them with established markers of cholecystitis. Moreover, it aims to define the optimal duration of oral antibiotic treatment for chronic bacterial cholecystitis in bears associated with bile farming. Thirty-nine adult, formerly bile-farmed Asiatic black bears (Ursus thibetanus) were examined under anesthesia and underwent percutaneous ultrasound guided cholecystocentesis. A total of 59 bile samples were collected with 20 animals sampled twice to evaluate the therapeutic success. All bile aspirates were assessed macroscopically and microscopically followed by submission for bacterial culture and antimicrobial sensitivity. In the majority of bears, samples with cytological evidence of bactibilia lacked inflammatory cells and did not always correlate with positive bacterial cultures. The most common bacterial isolates were Enterococcus spp, Streptococcus spp and Escherichia coli. Based on our findings, the optimal duration of antibiotic treatment for chronic bacterial cholecystitis is 30 days. Moreover, unlike Gamma-glutamyl Transferase (GGT) and gallbladder wall thickness, the organoleptic properties of bile were found to be reliable markers of chronic gallbladder inflammation with color and turbidity indicating cholestasis. The current study highlights the importance of cholecystocentesis for the management of gallbladder disease and provides initial results on the possible diagnostic value of macroscopic bile examination.

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.

Prolonged postoperative antibiotic administration reduces complications after medial thigh lift

There is widespread consensus that there is no indication for postoperative antibiotic administration after elective surgery. However, medial thigh lift (MTL) remains a procedure with a notoriously high rate of wound-healing disorders and infections. This study investigates the correlation between prolonged antibiotic administration and complications after MTL in massive weight loss patients. We performed a single-institution retrospective review of 121 patients undergoing MTL between 2009 and 2020. Data on postoperative outcome, demography, surgery and comorbidities were collected. All patients received intravenous antibiotics preoperatively. One group was continued on oral antibiotics for two weeks postoperatively. Complications and surgical site infections were observed and evaluated. There was no difference between the groups regarding age, BMI, or presence of obesity-associated risk factors. We observed complications in 76 patients (71%), with 60 (56%) minor and 16 (15%) major complications. The group without prolonged antibiotic administration had a higher number of total complications (OR 3.5; p = 0.0037), major complications (OR 4; p = 0.01), and wound infections (OR 6.8; p = 0.0004). Logistical regression analysis showed that this effect was independent of type of weight loss, resection volume, and age. Reduction of major infections by prolonged antibiotics was, however, dependent on BMI Δ. No side-effects associated with antibiotics were registered in this series. This study suggests that prolonged antibiotic administration may decrease complications in MTL. We thus continue to use prolonged antibiotic administration after MTL. Further research is needed to determine the optimal duration of antibiotic treatment. Level of Evidence: Level IV: therapeutic study

Superinfection associated with prolonged antibiotic use in non-ventilator associated hospital-acquired pneumonia.

Background Non-ventilator associated hospital-acquired pneumonia accounts for significant antibiotic use and is associated with a high rate of resistance emergence. However, the optimal duration of antibiotic treatment is uncertain, especially in cases of non-fermenting gram-negative bacilli. Objective To compare a short course (5-7days) to a prolonged course (10-14days) of antibiotics for non-ventilator associated hospital-acquired pneumonia. Methods Data collected retrospectively on patients completed treatment in a Malaysian tertiary hospital from January 2017 till December 2018. Regression analysis determined variables independently associated with clinical outcome. Main outcome measures Clinical resolution, superinfection, 30-day and 90-day all-cause mortality between short and prolonged courses. Results Of the 167 patients included, 112 patients were treated with a short course antibiotic, whereas 55 patients received a prolonged course of therapy. Neither short nor prolonged course group has a significantly higher rate of clinical resolution. Short course group had significantly higher mean ± SD antibiotic-free days (21.9 ± 3.5 versus 15.1 ± 6.2days, p < 0.001). Higher rate of superinfection was observed in prolonged course group compared to short course group (6.3% versus 18.2%, p = 0.027). For non-ventilator associated hospital-acquired pneumonia caused by non-fermenting gram-negative bacilli, the superinfection rate was higher in prolonged course group (35.7% versus 15.4%, p = 0.385) while 30-day mortality rate was higher in the short course group (38.5% versus 14.3%, p = 0.209). Non-fermenting gram-negative bacilli cause higher rate of superinfection (p = 0.010). Conclusion We found no clinical benefit as defined by clinical resolution and reduction in all-cause mortality in prolonging antimicrobial therapy. Superinfections emerge more frequently in prolonged course of antibiotic therapy and more likely to develop in non-fermenting gram-negative bacilli.

199. Short versus Extended Antibiotic Treatment with a Carbapenem for High-risk Febrile Neutropenia in Hematology Patients with Fever of Unknown Origin: A Randomized Multicenter Noninferiority Trial

BackgroundIn hematology patients with high risk neutropenia due to intensive chemotherapy the optimal antibiotic treatment duration for fever of unknown origin (FUO) is unknown. Early antibiotic discontinuation has been advocated to reduce unnecessary exposure to broad-spectrum antibiotics, but there is limited evidence for the safety of this strategy. We aimed to assess if short treatment with carbapenems is non-inferior to extended treatment for neutropenic patients with FUO.MethodsMulticenter, open-label, randomized clinical trial in 6 centers in the Netherlands. Hematology patients with FUO during high risk neutropenia (≥7 days) were eligible for participation. Eligible patients who gave informed consent were randomly assigned (1:1) to either the short treatment arm, where the carbapenem was discontinued after 72 hours, irrespective of presence of fever, or the extended treatment arm, where the carbapenem was continued for ≥ 9 days until afebrile for 5 days or end of neutropenia (EON), whichever came first. The primary endpoint was treatment failure defined as a composite of recurrent fever or a carbapenem-sensitive infection between day 4 and day 8 and septic shock or death from day 4 until EON. Secondary endpoints included all-cause and infection-related mortality until 30 days post-EON. We used 10% as noninferiority margin.Trial Intervention Flowchart ResultsBetween December 2014 and August 2019 292 patients were included. Risk of treatment failure in the modified intention-to-treat analysis (mITT) was 23.5% (32/136) in the short treatment versus 18.3% (24/131) in the extended treatment arm (adjusted risk difference (ARD) 3.7% (90% CI -2.6% to 9.9%)) and in the per-protocol analysis 27.9% (29/104) versus 18.2% (22/121) (ARD 8.9% (90% CI 0.6% to 17.2%). Short treatment was non-inferior to extended treatment in the mITT population, but not in the per protocol population.All-cause mortality until 30 days post-EON was significantly higher in the short treatment group: 3.7% (5/136) versus 0.8% (1/131) (ARD 2.8%, 95% CI 1.3 to 4.4%), but infection-related mortality until 30 days post-EON was not statistically different between the treatment arms.Primary and Secondary Endpoint Results Subgroup Analyses Results Bloodstream infections after day 3 ConclusionShort treatment with a carbapenem in neutropenic patients with fever was noninferior to extended treatment with regard to treatment failure.Conclusion Summary Disclosures All Authors: No reported disclosures

Clinical Characteristics of Spinal Epidural Abscess Accompanied by Bacteremia.

ObjectiveThe treatment of choice for spinal epidural abscess (SEA) generally is urgent surgery in combination with intravenous antibiotic treatment. However, the optimal duration of antibiotic treatment has not been established to date, although 4–8 weeks is generally advised. Moreover, some researchers have reported that bacteremia is a risk factor for failure of antibiotic treatment in SEA. In this study, we investigated the clinical characteristics of SEA accompanied by bacteremia and also determined whether the conventional 4–8 weeks of antibiotic treatment is sufficient. MethodsWe retrospectively reviewed the medical records and radiological data of 23 patients with bacterial SEA who underwent open surgery from March 2010 to April 2020. All patients had bacteremia preoperatively and underwent weeks of perioperative antibiotic treatments based on their identified organisms until all symptoms of infection disappeared. All patients underwent microbiological studies of peripheral blood, specimens from SEA and concomitant infections. The mean follow-up duration was 35.2 months, excluding three patients who died. ResultsThe male : female ratio was 15 : 8, and the mean age was 68.9 years. The SEA most commonly involved the lumbar spinal segment (73.9%), and the mean size was 2.9 vertebral body lengths. Mean time periods of 8.4 days and 16.6 days were required from admission to diagnosis and from admission to surgery, respectively. Concomitant infections more frequently resulted in delayed diagnosis (p=0.032), masking the symptoms of SEA. Methicillin-sensitive Staphylococcus aureus was the most commonly identified pathogen in both blood and surgical specimens. Seventeen patients (73.9%) showed no deficits at the final follow-up. The overall antibiotic treatment duration was a mean of 66.6 days, excluding three patients who died. This duration was longer than the conventionally advised 4–8 weeks (p=0.010), and psoas or paraspinal abscess required prolonged duration of antibiotic treatment (p=0.038). ConclusionSEA accompanied by bacteremia required a longer duration (>8 weeks) of antibiotic treatment. In addition, the diagnosis was more frequently delayed in patients with concomitant infections. The duration of antibiotic treatment should be extended for SEA with bacteremia, and a high index of suspicion is mandatory for early diagnosis, especially in patients with concomitant infections.

Impact of reducing the duration of antibiotic treatment on the long-term prognosis of community acquired pneumonia

BackgroundThe optimal duration of antibiotic treatment for community-acquired pneumonia (CAP) is not well established. The aim of this study was to assess the impact of reducing the duration of antibiotic treatment on long-term prognosis in patients hospitalized with CAP.MethodsThis was a multicenter study assessing complications developed during 1 year of patients previously hospitalized with CAP who had been included in a randomized clinical trial concerning the duration of antibiotic treatment. Mortality at 90 days, at 180 days and at 1 year was analyzed, as well as new admissions and cardiovascular complications. A subanalysis was carried out in one of the hospitals by measuring C-reactive protein (CRP), procalcitonin (PCT) and proadrenomedullin (proADM) at admission, at day 5 and at day 30.ResultsA total of 312 patients were included, 150 in the control group and 162 in the intervention group. Ninety day, 180 day and 1-year mortality in the per-protocol analysis were 8 (2.57%), 10 (3.22%) and 14 (4.50%), respectively. There were no significant differences between both groups in terms of 1-year mortality (p = 0.94), new admissions (p = 0.84) or cardiovascular events (p = 0.33). No differences were observed between biomarker level differences from day 5 to day 30 (CRP p = 0.29; PCT p = 0.44; proADM p = 0.52).ConclusionsReducing antibiotic treatment in hospitalized patients with CAP based on clinical stability criteria is safe, without leading to a greater number of long-term complications.

Short-course versus long-course antibiotic treatment in patients with uncomplicated gram-negative bacteremia: A systematic review and meta-analysis.

What is known and objectiveGram‐negative bacteremia remains a major health problem around the world. The optimal duration of antibiotic treatment has been poorly defined, and there are significant differences of opinion between clinicians. We conducted this systematic review and meta‐analysis to compare the clinical outcomes of short‐course and long‐course treatments in patients with uncomplicated gram‐negative bacteremia.MethodsWe searched public databases (PubMed, EMBASE and Cochrane Library) to identify eligible studies. The primary outcomes were all‐cause mortality and the incidence of recurrent bacteremia through day 30. We used the Cochrane risk of bias assessment tool to evaluate the risk of bias for randomized controlled trials (RCTs) and the Newcastle‐Ottawa Scale for non‐RCTs.Results and discussionSix studies involving 2689 patients were included in the systematic review and meta‐analysis. No significant difference was found between short‐course and long‐course antibiotic treatments in 30‐day mortality (risk ratio [RR] 0.85; 95% confidence interval [CI] 0.65‐1.13; P = .26), 30‐day recurrent bacteremia (RR 1.07; 95% CI 0.68‐1.67; P = .78), 90‐day mortality (RR 0.84; 95% CI 0.57‐1.24; P = .38), 90‐day recurrent bacteremia (RR 0.98; 95% CI 0.50‐1.89; P = .94), adverse events (RR 1.14; 95% CI 0.89‐1.45; P = .30), Clostridium difficile infection (RR 0.86; 95% CI 0.40‐1.86; P = .71) or resistance development (RR 1.19; 95% CI 0.66‐2.14; P = .57).What is new and conclusionShort‐course was non‐inferior to long‐course antibiotic treatments for patients with uncomplicated gram‐negative bacteremia. Considering the drug‐related side effects and cost‐effectiveness, a shorter duration of antibiotic treatment may be preferable for this particular population. However, additional high‐quality RCTs are needed to further assess whether a shorter course of antibiotic treatment is of greater benefit for patients with uncomplicated gram‐negative bacteremia.

Three-day antibiotic treatment for acute cholangitis due to choledocholithiasis with successful biliary duct drainage: A single-center retrospective cohort study

ObjectivesGiven that the optimal antibiotic treatment duration for acute cholangitis with successful biliary drainage remains unknown, this study aimed to validate whether antibiotic treatment duration could be reduced to ≤3 days among patients presenting the same. MethodsThis retrospective study included patients who presented with mild to moderate acute cholangitis due to choledocholithiasis who had undergone successful biliary drainage through endoscopic retrograde cholangiopancreatography (ERCP). After that, 30-day mortality rates and 3-month recurrence rates following short-course antibiotic treatment (SCT, ≤3 days) and long-course antibiotic treatment (LCT, ≥4 days) were compared. ResultsA total of 96 patients were analyzed, among whom 22 (22.9%) received SCT, and 74 (77.1%) received LCT. The SCT and LCT groups had a median antibiotic treatment duration of 1.5 (range 1–3) and seven (range 4–17) days, respectively. Moreover, the SCT and LCT groups exhibited no significant differences in cholangitis grades, 30-day mortality rates (0%, 0/22 and 2.7%, 2/74, respectively), 3-month recurrence rates, length of hospitalization, and acute bacteremic cholangitis rates. ConclusionsThis study suggests that antibiotic treatment for ≤3 days may be adequate for patients with mild to moderate acute cholangitis due to choledocholithiasis who had undergone successful biliary drainage.

The CABI Trial: an Unblinded Parallel Group Randomised Controlled Feasibility Trial of Long-Course Antibiotic Therapy (28 Days) Compared with Short Course (≤ 10 Days) in the Prevention of Relapse in Adults Treated for Complicated Intra-Abdominal Infection

PurposeRelapse after complicated intra-abdominal infection (cIAI) remains common after treatment. The optimal antibiotic treatment duration for cIAIs is uncertain, especially in cases where source control is not achieved. We hypothesised that in patients with cIAIs, regardless of source control intervention, there would be a lower relapse rate with long-course antibiotics (28 days) compared with short course (≤ 10 days). We piloted a trial comparing ≤ 10-day with 28-day antibiotic treatment for cIAI. MethodsA randomised controlled unblinded feasibility trial was conducted. Eligible participants were adult patients with a cIAI that were diagnosed ≤ 6 days prior to screening. Randomisation was to long-course (28 days) or short-course (≤10 days) antibiotic therapy. Choice of antibiotics was determined by the clinical team. Participants were followed up for 90 days. Primary outcomes were willingness of participants to be randomised and feasibility of trial procedures. ResultsIn total, 172 patients were screened, 84/172 (48.8%) were eligible, and 31/84 (36.9%) were randomised. Patients were assigned to either the short-course arm (18/31, 58.0%) or the long-course arm (13/31, 41.9%). One patient in the short-course arm withdrew after randomisation. In the short-course arm, 4/17 (23.5%) were treated for a cIAI relapse vs 0/13 (0.0%) relapses in the long-course arm. Protocol violations included deviations from protocol-assigned antibiotic duration and interruptions to antibiotic therapy. ConclusionsThis feasibility study identified opportunities to increase recruitment in a full trial. This study demonstrates completion of a randomised controlled trial to further evaluate if the optimum antibiotic duration for cIAIs is feasible. Trial RegistrationClinicalTrials.gov Identifier: NCT03265834

Two vs. three weeks of treatment with amoxicillin-clavulanate for stabilized community-acquired complicated parapneumonic effusions. A preliminary non-inferiority, double-blind, randomized, controlled trial.

BackgroundThe optimal duration of antibiotic treatment for complicated parapneumonic effusions (CPPEs) has not been properly defined. Our aim was to compare the efficacy of amoxicillin-clavulanate for 2 vs. 3 weeks in patients with CPPE (i.e. those which required chest tube drainage).MethodsIn this non-inferiority, randomized, double-blind, controlled trial, patients with community-acquired CPPE were recruited from two centers in Spain and, after having obtained clinical stability following 2 weeks of amoxicillin-clavulanate, they were randomly assigned to placebo or antibiotic for an additional week. The primary objective was clinical success, tested for a non-inferiority margin of<10%. Secondary outcomes were the proportion of residual pleural thickening of>10 mm at 3 months, and adverse events. The study was registered with EudraCT, number 2014-003137-25. We originally planned to randomly assign 284 patients.ResultsAfter recruiting 55 patients, the study was terminated early owing to slow enrolment. A total of 25 patients were assigned to 2 weeks and 30 patients to 3 weeks of amoxicillin-clavulanate. Clinical success occurred in the 25 (100%) patients treated for 2 weeks and 29 (97%) treated for 3 weeks (difference 3%, 95% CI −3 to 9.7%). Respective between-group differences in the rate of residual pleural thickening (−12%, 95%CI −39 to 14%) and adverse events (−7%, 95%CI −16 to 2%) did not reach statistical significance.ConclusionsIn this small series of selected adult patients with community-acquired CPPE, amoxicillin-clavulanate treatment could be safely discontinued by day 14 if clinical stability was obtained.