As antimicrobial resistance (AMR) escalates globally, examining antibiotic treatment durations for respiratory infections becomes increasingly pertinent, especially in the context of the COVID-19 pandemic. In a UK secondary care setting, this retrospective study was carried out to assess the appropriateness of antibiotic treatment durations-shorter (≤5 days) versus longer (6-7 days and >8 days)-for respiratory tract infections (RTIs) in 640 adults across 2019 and 2020, in accordance with local antimicrobial guidelines. The analysis employed these guidelines and clinical evidence to examine the effectiveness and suitability of antibiotic prescribing practices. This study considered the \'Shorter Is Better\' approach, noting an increased rate of patient discharges associated with shorter antibiotic regimens (≤5 days). It further demonstrates that shorter treatments are as effective as longer ones for conditions such as COPD exacerbation, COVID-19 pneumonia, and hospital-acquired pneumonia (HAP), except in cases of community-acquired pneumonia (CAP) and unspecified diagnoses. Nevertheless, this study raises concerns over an observed increase in mortality risk with shorter treatment durations. Although these mortality differences were not statistically significant and might have been influenced by the COVID-19 pandemic, the need for extended research with a larger sample size is highlighted to confirm these findings. This study also emphasises the critical need for accurate and specific diagnoses and considering risk assessments at admission, advocating for tailored, evidence-based antibiotic prescribing to ensure patient safety. It contributes to antimicrobial stewardship efforts by reinforcing the importance of adapting antibiotic use to current healthcare challenges and promoting a global commitment to fight antimicrobial resistance. This approach is crucial for enhancing patient outcomes and saving lives on a global scale.

BACKGROUND: New skin and soft tissue infections (SSTI) guidelines were published in 2019 in France, changing the recommended duration for antibiotic treatment. The objective of the present study was to assess the impact of the publication of the 2019 French guidelines on SSTIs on the duration of antibiotic prescription for erysipelas.
METHODS: In a before-after study (a year before and a year after April 1st, 2019), we included all adult patients diagnosed with erysipelas in Reims University Hospital medical wards and the emergency department. We retrospectively retrieved antibiotic prescription duration in the patients\' medical files.
RESULTS: Among 50 patients in the \"before\" and 39 in the \"after\" group, the mean duration of antibiotic prescription was significantly shorter in the \"after\" group (9.4 ± 2.8 vs. 12.4 ± 3.8 days, p = 0.0001).
CONCLUSIONS: A 25% decrease in the duration of antibiotic prescription for erysipelas was observed following the implementation of these guidelines, providing useful information for an antibiotic stewardship policy.

OBJECTIVE: Cerebrospinal fluid (CSF) white blood cell (WBC) count, neutrophil percentage, protein concentration, and glucose level are typically measured at diagnosis and serially during the treatment of CSF shunt infections. The objective of this retrospective cohort study was to describe the longitudinal profile of CSF parameters in children with CSF shunt infections and assess their association with treatment and outcome.
METHODS: Participants were children treated at 11 tertiary pediatric hospitals in Canada and the United States for CSF shunt infection, from July 1, 2013, through June 30, 2019, with hardware removal, external ventricular drain placement, intravenous antibiotics, and subsequent permanent shunt reinsertion. The relationship between CSF parameters and a complicated course (a composite outcome representing children with at least one of the following: contiguous soft-tissue infection, worsening hydrocephalus, CSF leak, intracranial bleed, brain abscess, venous thrombosis, reinfection after insertion of the new shunt, other complication, ICU admission, or death) was analyzed.
RESULTS: A total of 109 children (median age 2.8 years, 44% female) were included in this study. CSF pleocytosis, elevated protein, and hypoglycorrhachia had sensitivities of 69%, 47%, and 38% for the diagnosis of culture-confirmed CSF shunt infection, respectively. The longitudinal profile of the neutrophil percentage followed a monotonic trend, decreasing by 1.5% (95% CI 1.0%-2.0%, p < 0.0001) per day over the course of treatment. The initial WBC count differed significantly between pathogens (p = 0.011), but the proportion of neutrophils, protein concentration, and glucose level did not, and was lowest with Cutibacterium acnes. The duration of antibiotic treatment and the time to shunt reinsertion were longer in patients with a higher initial neutrophil percentage. Fifty-eight patients (53%) had one or more complications during their admission. A neutrophil percentage > 44% (Youden index) in the initial CSF sample was associated with a 1.8-fold (95% CI 1.2- to 2.8-fold) higher relative risk of a complicated course. In a random-intercept, random-slope linear mixed-effects model, the longitudinal neutrophil trajectory differed significantly between patients with and without complications (p = 0.030).
CONCLUSIONS: A higher proportion of neutrophils in the CSF at diagnosis was associated with a complicated clinical course. Other CSF parameters were associated with treatment and outcome; however, wide variability in values may limit their clinical utility.

UNASSIGNED: To describe the protocol for a multi-centre randomised controlled trial to determine whether treatment protocols monitoring daily CRP (C-reactive protein) or PCT (procalcitonin) safely allow a reduction in duration of antibiotic therapy in hospitalised adult patients with sepsis.
UNASSIGNED: Multicentre three-arm randomised controlled trial.
UNASSIGNED: UK NHS hospitals.
UNASSIGNED: Hospitalised critically ill adults who have been commenced on intravenous antibiotics for sepsis.
UNASSIGNED: Three protocols for guiding antibiotic discontinuation will be compared: (a) standard care; (b) standard care + daily CRP monitoring; (c) standard care + daily PCT monitoring. Standard care will be based on routine sepsis management and antibiotic stewardship. Measurement of outcomes and costs. Outcomes will be assessed to 28 days. The primary outcomes are total duration of antibiotics and safety outcome of all-cause mortality. Secondary outcomes include: escalation of care/re-admission; infection re-lapse/recurrence; antibiotic dose; length and level of critical care stay and length of hospital stay. Ninety-day all-cause mortality rates will also be collected. An assessment of cost effectiveness will be performed.
UNASSIGNED: In the setting of routine NHS care, if this trial finds that a treatment protocol based on monitoring CRP or PCT safely allows a reduction in duration of antibiotic therapy, and is cost effective, then this has the potential to change clinical practice for critically ill patients with sepsis. Moreover, if a biomarker-guided protocol is not found to be effective, then it will be important to avoid its use in sepsis and prevent ineffective technology becoming widely adopted in clinical practice.

Introduction and Objective: Postoperative infection and sepsis account for the most common complications following percutaneous nephrolithotomy (PCNL), as high as 14% in low-risk patients. Although the American Urological Association (AUA) recommends perioperative antibiotics for 24 hours or less for PCNL, practice patterns vary regarding duration of antibiotic therapy. We aimed to compare the efficacy of 24-hour antibiotic coverage vs short-course protocol of antibiotic prophylaxis for PCNL. Materials and Methods: Low-risk patients with a sterile preoperative urine culture undergoing PCNL were prospectively randomized to antibiotics for up to 24 hours after procedure (24Hr) or continued until external urinary catheters were removed (CR) study groups. Patients were given a first generation cephalosporin, or ciprofloxacin in patients with penicillin allergy. Exclusion criteria included age <18 years, receiving antibiotics immediately before the procedure, history of urosepsis, presence of indwelling catheter >1 week, multistage procedure, immunosuppression, pregnancy, multiple antibiotic allergies, and patients who are breastfeeding. Results: Ninety-eight patients were randomized to either 24Hr (n = 49) or CR (n = 49). Mean duration of antibiotic administration was 20.6 and 34.0 hours in the 24Hr and CR groups (p = 0.04), respectively. Age, comorbidities, stone size, operative time, number of punctures, dilations, and proportion of \"tubeless\" procedures were similar between groups. There were no differences in febrile episodes, rates of systemic inflammatory response syndrome, bacteremia, or culture-proven postoperative urinary tract infection between the 24Hr and CR groups. Overall complication rates were similar between groups. In a subgroup analysis which excluded \"tubeless\" patients (24 and 29 patients in 24Hr and CR groups, respectively), no differences were seen in postoperative outcomes. Conclusions: In a randomized, prospective study, we found that a 24-hour protocol for antibiotic prophylaxis is not associated with increased risk of infection-related events compared to giving antibiotics until external catheters are removed in patients with low infectious risk undergoing PCNL. Clinicaltrials.gov: NCT02579161.

BACKGROUND: Few studies address the appropriate duration of post-surgical antibiotic therapy for orthopedic infections; with or without infected residual implants. We perform two similar randomized-clinical trials (RCT) to reduce the antibiotic use and associated adverse events.
METHODS: Two unblinded RCTs in adult patients (non-inferiority with a margin of 10%, a power of 80%) with the primary outcomes \"remission\" and \"microbiologically-identical recurrences\" after a combined surgical and antibiotic therapy. The main secondary outcome is antibiotic-related adverse events. The RCTs allocate the participants between 3 vs. 6 weeks of post-surgical systemic antibiotic therapy for implant-free infections and between 6 vs. 12 weeks for residual implant-related infections. We need a total of 280 episodes (randomization schemes 1:1) with a minimal follow-up of 12 months. We perform two interim analyses starting approximately after 1 and 2 years. The study approximatively lasts 3 years.
CONCLUSIONS: Both parallel RCTs will enable to prescribe less antibiotics for future orthopedic infections in adult patients.
BACKGROUND: ClinicalTrial.gov NCT05499481. Registered on 12 August 2022.
METHODS: 2 (19 May 2022).

The optimal duration of antimicrobial therapy for urinary tract infections (UTIs) in men remains controversial.
To compare 7 days to 14 days of total antibiotic treatment for febrile UTIs in men, this multicenter randomized, double-blind. placebo-controlled noninferiority trial enrolled 282 men from 27 centers in France. Men were eligible if they had a febrile UTI and urine culture showing a single uropathogen. Participants were treated with ofloxacin or a third-generation cephalosporin at day 1, then randomized at day 3-4 to either continue ofloxacin for 14 days total treatment, or for 7 days followed by placebo until day 14. The primary endpoint was treatment success, defined as a negative urine culture and the absence of fever and of subsequent antibiotic treatment between the end of treatment and 6 weeks after day 1. Secondary endpoints included recurrent UTI within weeks 6 and 12 after day 1, rectal carriage of antimicrobial-resistant Enterobacterales, and drug-related events.
Two hundred forty participants were randomly assigned to receive antibiotic therapy for 7 days (115 participants) or 14 days (125 participants). In the intention-to-treat analysis, treatment success occurred in 64 participants (55.7%) in the 7-day group and in 97 participants (77.6%) in the 14-day group (risk difference, -21.9 [95% confidence interval, -33.3 to -10.1]), demonstrating inferiority. Adverse events during antibiotic therapy were reported in 4 participants in the 7-day arm and 7 in the 14-day arm. Rectal carriage of resistant Enterobacterales did not differ between both groups.
A treatment with ofloxacin for 7 days was inferior to 14 days for febrile UTI in men and should therefore not be recommended.
NCT02424461; Eudra-CT: 2013-001647-32.

Background: Current guidelines recommend a seven-day course of antibiotic therapy for patients with ventilator-associated pneumonia (VAP). However, clinical and microbiologic resolution of infection may occur much sooner than seven days, particularly in patients with early VAP. Shortening the course of antibiotic therapy for early VAP likely results in lower antibiotic-associated complications, but it is unclear whether VAP recurrence rates will be higher in patients receiving fewer days of therapy. We propose to compare four days versus seven days of antibiotic therapy for early VAP in surgical patients in a multicenter, pragmatic, randomized clinical trial. Patients and Methods: Eligible patients admitted to a surgical intensive care unit with early VAP, defined as VAP occurring within two to seven days of intubation, will be randomized to receive four or seven days of antibiotic therapy. The two primary outcomes are: VAP recurrence, defined as VAP occurring two to 14 days after completion of initial therapy and antibiotic-free days, defined as the number of days without receiving any antibiotic agents within 30 days from completion of initial therapy. Data will be analyzed using both intention-to-treat and per-protocol strategies. Power analysis was performed assuming non-inferiority of four days vs. seven days for VAP recurrence and superiority of four days versus seven days for antibiotic-free days. The total sample size to detect a 10% difference between groups with 80% power and assuming a 10% dropout rate is 458 patients. Three separate data analyses are planned throughout the trial and sample size will be re-calculated at each interim analysis. Conclusions: The Duration of Antibiotic Therapy for Early VAP (DATE) Trial will enroll surgical patients with early VAP to analyze whether a shorter duration of antibiotic therapy results in similar clinical outcomes while decreasing antibiotic exposure.

UNASSIGNED: Whether increased antibiotic duration is necessary for surgical site infection (SSI) in patients after neck surgery is unclear. We investigated the characteristics of SSI, and the impact of SSI on increased antibiotic duration among patients with laryngocarcinoma (LC).
UNASSIGNED: A retrospective cohort study including consecutive LC patients ≥18 years, undergoing surgery without remote metastasis was conducted from October 2015 to February 2022 in the Department of Otolaryngology-Head and Neck Surgery, Chengdu Second People\'s Hospital. SSI was defined according to current guidelines. Patients were stratified into 3 groups including no-infection, lower respiratory tract infection (LRTI) and SSI. Patient characteristics was recorded. Patients were followed up until discharge. A multiple linear regression model including SSI and other factors including age, sex, comorbidity and antibiotic treatments was performed to explore the impact of SSI on increased antibiotic duration among LC patients with postoperative infection.
UNASSIGNED: A total of 88 patients were included, with 26 (29.5%) in no-infection group, 38 (43.2%) in LRTI group, and 24 (27.3%) in SSI group. Laryngocutaneous fistula occurred in 8 (33.3%) patients with SSI. Thirteen (34.2%) patients in LRTI group and 9 (37.5%) patients in SSI group experienced postoperative infection within 2 days after surgery, and antibiotic susceptibility tests were performed in 18 (47.4%) and 12 (50.0%) patients in LRTI and SSI group, respectively (P>0.05 for both). Levofloxacin and cefoperazone-sulbactam were the most commonly used antibiotics for postoperative infection in both LRTI and SSI groups (P>0.05 for both), irrespective of antibiotic susceptibility tests or not. The postoperative antibiotic duration in SSI group was significantly longer than that in LRTI group (13.62±4.28 days in SSI vs. 11.22±3.64 days in LRTI, P=0.021). A multiple linear regression analysis including SSI, age, sex, diabetes, antibiotic susceptibility test and hypoalbuminemia showed that, SSI was independently associated with increased antibiotic duration with LRTI as the reference among LC patients diagnosed [regression coefficient β=3.02, 95% confidence interval (CI): 1.01-5.03, P=0.004], whereas antibiotic susceptibility test was not (P=0.467).
UNASSIGNED: SSI may be independently associated with increased postoperative antibiotic duration in patients with LC with or without antibiotic susceptibility test.

Treating pneumonia in old patients remains challenging for clinicians. Moreover, bacterial antimicrobial resistance is a major public health threat.
The PROPAGE study evaluated the interest of a strategy using serial measurements of procalcitonin (PCT) to reduce the duration of antibiotic therapy in old patients with pneumonia.
PROPAGE took place from Dec.-2013 to Jun.-2016 in eight French geriatric units. It was a prospective, comparative, randomised, open-label study involving old patients (≥ 80 years) who had initiated antibiotic treatment for pneumonia in the previous 48 h. PCT was monitored in all patients and two decision-making PCT-based algorithms guided antibiotic therapy in patients from the PCT group.
107 patients were randomised (PCT, n = 50; Control, n = 57). Antibiotic therapy exposure was reduced in the PCT group as compared to the Control group (median duration of antibiotic therapy, 8 vs. 10 days [rank-test, p = 0.001]; antibiotic persistence rates on Days 6 and 8, 54% and 44% vs. 91% and 72%) and no significant difference was found in recovery rate (84% vs. 89.5%; Pearson Chi² test, p = 0.402).
Although, the superiority of the strategy was not tested using a composite criterion combining antibiotic therapy duration and recovery rate was not tested due to the small sample size, the present study showed that monitoring associated with PCT-guided algorithm could help shorten antibiotic treatment duration in the very old patients without detrimental effects. Measuring PCT levels between Day 4 and Day 6 could be helpful when making the decision regarding antibiotic discontinuation.
NCT02173613. This study was first registered on 25/06/2014.