Appropriate Duration Of Antimicrobial Therapy Research Articles

When to Stop Antibiotics in the Critically Ill?

Over the past century, antibiotic usage has skyrocketed in the treatment of critically ill patients. There have been increasing calls to establish guidelines for appropriate treatment and durations of antibiosis. Antibiotic treatment, even when appropriately tailored to the patient and infection, is not without cost. Short term risks-hepatic/renal dysfunction, intermediate effects-concomitant superinfections, and long-term risks-potentiating antimicrobial resistance (AMR), are all possible consequences of antimicrobial administration. These risks are increased by longer periods of treatment and unnecessarily broad treatment courses. Recently, the literature has focused on multiple strategies to determine the appropriate duration of antimicrobial therapy. Further, there is a clinical shift to multi-modal approaches to determine the most suitable timepoint at which to end an antibiotic course. An approach utilising biomarker assays and an inter-disciplinary team of pharmacists, nurses, physicians, and microbiologists appears to be the way forward to develop sound clinical decision-making surrounding antibiotic treatment.

Antimicrobial therapy outcomes in acute cholangitis: Hilar multiple obstructions versus single hilar and common bile duct obstructions.

The appropriate duration of antimicrobial therapy for acute cholangitis (AC) arising from multiple hilar biliary obstructions as opposed to simple obstruction in the extrahepatic bile duct has not been established. This study assessed the efficacy of the duration of antimicrobial treatments in the Tokyo Guidelines 2018 for AC based on the cause and site of obstruction. This single-center retrospective study involved patients with AC who underwent successful biliary drainage and completed a 7-day or shorter antimicrobial treatment. Patients were categorized into three groups: Group 1, bile duct stone or benign obstruction; Group 2, simple biliary obstruction due to malignancy; and Group 3, multiple hilar biliary obstruction due to malignancy. The primary outcome was clinical cure rate, and the secondary outcomes were 3-month recurrence rate and length of hospital stay. A total of 373 patients were selected. Patients in Group 3 were younger or had Charlson Comorbidity Index ≥4, and had fewer positive blood cultures. In Group 3, the clinical cure rate (87.1%) and 3-month recurrence rate (32.3%) were less favorable than those in the other groups. In Group 1, the clinical cure rate was significantly higher (98.1%, P = 0.02) with a much lower 3-month recurrence rate of only 3.4% (P < 0.001) than that in the other groups. The median hospital stay for all groups was 7 days. This study suggests that the outcomes in Group 3 may be worse than those in Groups 1 or 2, regardless of the duration of the antibiotic treatment.

Clinical and Laboratory Features of Invasive Group A Streptococcal Infections: 8 Years Experience

Objective:Invasive infections caused by group A streptococci, including bacteremia, pneumonia, sepsis, necrotizing fasciitis, streptococcal toxic shock syndrome, and focal infections, are the significant causes of mortality and morbidity worldwide. This study aimed to assess the clinical and laboratory features and management of children with invasive group A streptococci infections.Materials and Methods:A descriptive observational study was conducted on children younger than 18 years with invasive group A streptococci infection in a single center between 2012 and 2019. The clinical and laboratory features, treatment options, and patient outcomes were evaluated retrospectively.Results:Forty-nine patients diagnosed with an invasive group A streptococci infection were analyzed. Among them, 28 (57.1%) were boys and 21 (42.9%) were girls, with a median age of 84 months (IQR: 48-150). Group A streptococci strains were found to be isolated mainly from the skin and soft tissue abscesses (60.7%). It was found that 21 (42.9%) of the cases were hospitalized, and the median duration of hospitalization was 7 (IQR: 5-11) days. It was noted that all of the cases were treated, and infection-related mortality was not observed in any patient.Conclusions:For correct management of invasive group A streptococci infections, timely diagnosis, appropriate duration of antimicrobial therapy, and surgical intervention in selected cases are required. It is thought that examining this issue in future studies may provide clues regarding the localization, severity, management of the infection clinic, and treatment.

Clinical and Laboratory Features of Invasive Group A Streptococcal Infections: 8 Years Experience.

Invasive infections caused by group A streptococci, including bacteremia, pneumonia, sepsis, necrotizing fasciitis, streptococcal toxic shock syndrome, and focal infections, are the significant causes of mortality and morbidity worldwide. This study aimed to assess the clinical and laboratory features and management of children with invasive group A streptococci infections. A descriptive observational study was conducted on children younger than 18 years with invasive group A streptococci infection in a single center between 2012 and 2019. The clinical and laboratory features, treatment options, and patient outcomes were evaluated retrospectively. Forty-nine patients diagnosed with an invasive group A streptococci infection were analyzed. Among them, 28 (57.1%) were boys and 21 (42.9%) were girls, with a median age of 84 months (IQR: 48-150). Group A streptococci strains were found to be isolated mainly from the skin and soft tissue abscesses (60.7%). It was found that 21 (42.9%) of the cases were hospitalized, and the median duration of hospitalization was 7 (IQR: 5-11) days. It was noted that all of the cases were treated, and infection-related mortality was not observed in any patient. For correct management of invasive group A streptococci infections, timely diagnosis, appropriate duration of antimicrobial therapy, and surgical intervention in selected cases are required. It is thought that examining this issue in future studies may provide clues regarding the localization, severity, management of the infection clinic, and treatment.

184. Staphylococcus aureus Bacteremia Management and Outcomes Following Infectious Disease Consult Over Time at a Tertiary Care Center in Canada

Abstract Background Staphylococcus aureus bacteremia (SAB) is associated with high morbidity and mortality. Infectious disease consultation (IDC) is associated with increased adherence to guideline management and improved patient outcomes. We describe the IDC rate over time and impact of IDC on the management and outcomes of patients with SAB. Methods This retrospective chart review includes adult patients (≥ 18 years) hospitalized at the University of Alberta Hospital, Edmonton, Canada who had at least 1 blood culture growing Staphylococcus aureus during two time periods (A: Jan 2010 to Dec 2012; B: Jan to Oct 2020). Patients who died or were made palliative within 48hrs following bacteremia were excluded. Descriptive statistics were used to compare appropriateness of SAB management and outcomes in patients receiving IDC and those who did not (NIDC). Results 325 patients in period A and 129 in period B were included. Baseline demographics were similar. IDC rate increased from 63% to 88% (p&amp;lt; 0.001) between the study periods. IDC was associated with increased odds of receiving an echocardiogram (OR=3.56, 95% CI 2.22 – 5.57; OR=20.4, 95% 4.13 – 110.6, p&amp;lt; 0.001) and appropriate duration of antimicrobial therapy (OR=6.74, 95% 3.93 – 11.54; OR=43.2, 95% 5.72 – 529.5, p&amp;lt; 0.001) between study periods. Mean length of stay decreased in patients receiving IDC (44.8 vs 28.1 days, p=0.005) and increased in NIDC patients (19.9 vs 28.7 days, p=0.216). IDC was associated with lower 30-day mortality in period A (OR=3.53, 95% 1.95 – 6.36), however this association was not observed in period B (OR=1.43, 95% 0.40 – 5.56). There was a trend towards decreased odds of mortality in patients receiving early IDC (≤2 days from bacteremia, n=65) compared to late IDC (≥3 days from bacteremia, n=45) (OR=2.59, 95% 0.95 – 7.10, p=0.077). Conclusion Our centre’s IDC rate for SAB increased over time without specific intervention. IDC increased the odds of appropriate SAB management and was associated with decreased length of stay in period B. IDC was associated with lower 30-day mortality in period A and trended towards lower mortality in period B. Specifically, early IDC decreased odds of 30-day mortality compared to late IDC. These results suggest that routine early IDC be part of SAB management. Disclosures All Authors: No reported disclosures

La polmonite acquisita in comunità

Community-acquired pneumonia (CAP) is one of the most common serious infections in children. The appropriate duration of antimicrobial therapy is unclear. In current practice antibiotic treatment courses of 10 days are prescribed in mild-moderate CAP, while up to 14-21-day courses in severe and complicated cases. The results of the SAFER (Short-Course Antimicrobial Therapy for Paediatric Respiratory Infections) study found that the “short therapy” appeared to be comparable to standard care for the treatment of previously healthy children with CAP not requiring hospitalization. Clinical practice guidelines should recommend 5 days of amoxicillin for paediatric pneumonia management in accordance with antimicrobial stewardship principles.

Antibiotic Therapy for 6 or 12 Weeks for Prosthetic Joint Infection

BackgroundThe management of prosthetic joint infection usually consists of a combination of surgery and antimicrobial therapy. The appropriate duration of antimicrobial therapy for this indication remains unclear.MethodsWe performed an open-label, randomized, controlled, noninferiority trial to compare 6 weeks with 12 weeks of antibiotic therapy in patients with microbiologically confirmed prosthetic joint infection that had been managed with an appropriate surgical procedure. The primary outcome was persistent infection (defined as the persistence or recurrence of infection with the initial causative bacteria, with an antibiotic susceptibility pattern that was phenotypically indistinguishable from that at enrollment) within 2 years after the completion of antibiotic therapy. Noninferiority of 6 weeks of therapy to 12 weeks of therapy would be shown if the upper boundary of the 95% confidence interval for the absolute between-group difference (the value in the 6-week group minus the value in the 12-week group) in the percentage of patients with persistent infection within 2 years was not greater than 10 percentage points.ResultsA total of 410 patients from 28 French centers were randomly assigned to receive antibiotic therapy for 6 weeks (205 patients) or for 12 weeks (205 patients). Six patients who withdrew consent were not included in the analysis. In the main analysis, 20 patients who died during follow-up were excluded, and missing outcomes for 6 patients who were lost to follow-up were considered to be persistent infection. Persistent infection occurred in 35 of 193 patients (18.1%) in the 6-week group and in 18 of 191 patients (9.4%) in the 12-week group (risk difference, 8.7 percentage points; 95% confidence interval, 1.8 to 15.6); thus, noninferiority was not shown. Noninferiority was also not shown in the per-protocol and sensitivity analyses. We found no evidence of between-group differences in the percentage of patients with treatment failure due to a new infection, probable treatment failure, or serious adverse events.ConclusionsAmong patients with microbiologically confirmed prosthetic joint infections that were managed with standard surgical procedures, antibiotic therapy for 6 weeks was not shown to be noninferior to antibiotic therapy for 12 weeks and resulted in a higher percentage of patients with unfavorable outcomes. (Funded by Programme Hospitalier de Recherche Clinique, French Ministry of Health; DATIPO ClinicalTrials.gov number, NCT01816009.)

Trial of Short-Course Antimicrobial Therapy for Intraabdominal Infection

BackgroundThe successful treatment of intraabdominal infection requires a combination of anatomical source control and antibiotics. The appropriate duration of antimicrobial therapy remains unclear.MethodsWe randomly assigned 518 patients with complicated intraabdominal infection and adequate source control to receive antibiotics until 2 days after the resolution of fever, leukocytosis, and ileus, with a maximum of 10 days of therapy (control group), or to receive a fixed course of antibiotics (experimental group) for 4±1 calendar days. The primary outcome was a composite of surgical-site infection, recurrent intraabdominal infection, or death within 30 days after the index source-control procedure, according to treatment group. Secondary outcomes included the duration of therapy and rates of subsequent infections.ResultsSurgical-site infection, recurrent intraabdominal infection, or death occurred in 56 of 257 patients in the experimental group (21.8%), as compared with 58 of 260 patients in the control group (22.3%) (absolute difference, −0.5 percentage point; 95% confidence interval [CI], −7.0 to 8.0; P=0.92). The median duration of antibiotic therapy was 4.0 days (interquartile range, 4.0 to 5.0) in the experimental group, as compared with 8.0 days (interquartile range, 5.0 to 10.0) in the control group (absolute difference, −4.0 days; 95% CI, −4.7 to −3.3; P<0.001). No significant between-group differences were found in the individual rates of the components of the primary outcome or in other secondary outcomes.ConclusionsIn patients with intraabdominal infections who had undergone an adequate source-control procedure, the outcomes after fixed-duration antibiotic therapy (approximately 4 days) were similar to those after a longer course of antibiotics (approximately 8 days) that extended until after the resolution of physiological abnormalities. (Funded by the National Institutes of Health; STOP-IT ClinicalTrials.gov number, NCT00657566.)

Acute Bacterial Sinusitis in Children

On the basis of strong research evidence, the pathogenesis of sinusitis involves 3 key factors: sinusostia obstruction, ciliary dysfunction, and thickening of sinus secretions. On the basis of studies of the microbiology of otitis media, H influenzae is playing an increasingly important role in the etiology of sinusitis, exceeding that of S pneumoniae in some areas, and b-lactamase production by H influenzae is increasing in respiratory isolates in the United States. On the basis of some research evidence and consensus,the presentation of acute bacterial sinusitis conforms to 1 of 3 predicable patterns; persistent, severe, and worsening symptoms. On the basis of some research evidence and consensus,the diagnosis of sinusitis should be made by applying strict clinical criteria. This approach will select children with upper respiratory infection symptoms who are most likely to benefit from an antibiotic. On the basis of some research evidence and consensus,imaging is not indicated routinely in the diagnosis of sinusitis. Computed tomography or magnetic resonance imaging provides useful information when complications of sinusitis are suspected. On the basis of some research evidence and consensus,amoxicillin-clavulanate should be considered asa first-line agent for the treatment of sinusitis.

Use of the clinical pulmonary infection score to guide therapy for ventilator-associated pneumonia risks antibiotic overexposure in patients with trauma

The clinical pulmonary infection score (CPIS) has been advocated to guide both the diagnosis and duration of therapy in ventilator-associated pneumonia (VAP). However, the clinical, physiologic, and radiologic components of the CPIS may be difficult to differentiate from the systemic effects of injury and inflammation, unnecessarily prolonging VAP therapy. This study evaluates the use of CPIS in determining the appropriate duration of antimicrobial therapy for VAP in patients with critical illness and trauma. Patients with VAP (≥10 CFU/mL in bronchoalveolar lavage [BAL] effluent) over 6 years were evaluated. Duration of antimicrobial therapy was determined by microbiologic resolution (≤10 CFU/mL) on repeated BAL. Recurrence was defined as >10 CFU/mL on BAL performed within 2 weeks of appropriate therapy. A CPIS of less than 6 was used as a threshold for VAP resolution. Of the patients with VAP, 1,028 were identified: 523 had community-acquired pathogens (mean CPIS, 6.9), and 505 had hospital-acquired (HA) pathogens (mean CPIS, 6.3). Using a CPIS of less than 6 yielded a sensitivity and specificity of 69% and 51% for community-acquired pathogens and 72% and 53% for HA pathogens, respectively. Antimicrobial therapy would have continued inappropriately in 59% of patients. Overall recurrence was 1%, occurring only with HA pathogens (mean CPIS, 5.9). CPIS should not be used to determine VAP resolution in patients with critical injury and trauma. It cannot reliably differentiate VAP from the systemic inflammatory response syndrome in the face of confounding clinical factors. Using CPIS to determine appropriate duration of antimicrobial therapy for patients with trauma is costly and could be harmful by unnecessarily prolonging exposure to antibiotics. Therapeutic study, level III.

Causative Pathogen Dictates Optimal Duration of Antimicrobial Therapy for Ventilator-Associated Pneumonia in Trauma Patients

Recent ventilator-associated pneumonia (VAP) guidelines recommend considering abbreviated therapy in patients with non-Pseudomonas aeruginosa VAP if clinical signs resolve. However, using an arbitrary day cutoff or clinical signs can be suboptimal for some, especially multiply injured patients, resulting in relapse and/or antibiotic resistance. Previously, we showed that repeat bronchoalveolar lavage (BAL) could guide antimicrobial duration for community-acquired VAP in trauma patients. The purpose of this study was to determine the appropriate duration of antimicrobial therapy for VAP in trauma patients secondary to hospital-acquired pathogens. Patients with VAP secondary to MRSA, Pseudomonas aeruginosa (PA), Acinetobacter baumannii (AB), Stenotrophomonas maltophilia (SM), or Enterobacteriaceae (ENB) during 6 years were evaluated. All received empiric antimicrobial therapy based on duration of ICU stay. Therapy was tailored based on culture data. Repeat BAL was performed on day 4 of appropriate therapy. Microbiological resolution was defined as ≤10(3) colony-forming units/mL. Recurrence was defined as ≥10(5) colony-forming units/mL on subsequent BAL performed within 2 weeks after completion of appropriate therapy. Six hundred and fifty-nine patients were identified. Seventy-seven percent of patients underwent repeat BAL: 96 with MRSA, 100 with AB, 139 with PA, 50 with SM, and 120 with ENB. The majority of patients with MRSA or PA achieved microbiological resolution after 14 days. Nearly 60% of patients with AB, SM, or ENB achieved microbiological resolution after 10 days. Overall recurrence was 2%. Repeat BAL provides objective evidence for VAP resolution in the face of potentially confounding clinical factors. Hospital-acquired VAP can be managed effectively by a defined course of therapy with a low recurrence. Duration of antimicrobial therapy for VAP in trauma patients should be dictated by the causative pathogen.

Contemporary management of and outcomes from cardiac device related infections

To describe the incidence and management of cardiac device infection. Infection is a serious, potentially fatal complication of device implantation. The numbers of device implants and infections are rising. Optimal care of device infection is not well defined. We retrospectively identified cases of device infection at our institution between 2000 and 2007 by multiple source record review, and active surveillance. Device infection was related to demographics, clinical, and procedural characteristics. Descriptive analysis was performed. From 2000 to 2007, a total of 2029 permanent pacemakers and 1076 biventricular/implantable cardioverter-defibrillators (ICDs) or ICDs were implanted. Thirty-nine cases of confirmed device infections were identified--27 pacemaker and 12 bivent/ICD or ICD infections, giving an infection rate of 1.25%. Median time from implant or revision to presentation was 150 days (range 2915 days, IQR25% 35-IQR75% 731). Ninety percent of patients presented with generator-site infections. The most common organism was methicillin-sensitive Staphylococcus aureus (30.8%), followed by coagulase negative Staphylococcus (20.5%). Complete device extraction occurred in 82%. Of these, none had relapse, and mortality was 7.4% (n = 2/27). With partial removal or conservative therapy (n = 13), relapse occurred in 67% (n = 8/12), with mortality of 8.4% (n = 1/12). Median duration of antibiotics was 42 days (range 47 days, IQR25% 28-IQR75% 42 days). Re-implantation of a new device occurred in 54%, at a median of 28 days (range 73 days, IQR25% 8.5-IQR75% 35 days). Methicillin-Resistant Staphylococcus Aureus infection predicted mortality (P < 0.004, RR 37, 95% CI 5.3-250). Median follow-up was 36 months. Cardiac device infection is a rare complication, with significant morbidity and mortality. Complete hardware removal with appropriate duration of antimicrobial therapy results in the best outcomes for patients.

Role of multiple site blood cultures to document the clearance of bacteremia in neonates

To evaluate the usefulness of two-site blood cultures for the documentation of bacterial clearance during initial treatment of culture proven neonatal sepsis. Clinical data were prospectively collected for 216 neonates who had blood cultures drawn for evaluation of possible sepsis. A positive diagnostic blood culture was followed by repeat blood cultures from two different peripheral sites after initiation of antimicrobial therapy. Follow-up two-site cultures were drawn on 25 occasions at a median interval of 3 days after start of antimicrobial therapy for culture-proven sepsis in 15 neonates. On 12 occasions, follow-up blood cultures were both negative. On eight occasions, follow-up blood cultures grew the same organisms from both sites. However, follow-up two-site cultures on five occasions in four of the 15 infants grew organisms from one site but not the second site. Two-site blood cultures seem necessary to document bacterial clearance in response to antimicrobial therapy for culture-proven sepsis, and may help determine the appropriate duration of antimicrobial therapy by reducing false-negative results.