Discontinuation Of Antibiotics Research Articles

Predictors of treatment failure following early antibiotic discontinuation in culture-negative, ventilator-associated pneumonia: an observational study.

Early antibiotic discontinuation in clinically suspected ventilator-associated pneumonia (VAP) may lead to infection relapse/recurrence and increase mortality. This study aimed to evaluate the incidence and potential predictors of treatment failure with this approach. A retrospective observational study was conducted between September 2014 and November 2016 in a mixed intensive care unit. We included clinically suspected VAP patients whose quantitative sputum cultures from endotracheal aspirate were negative, allowing antibiotic discontinuation within 24 hours. Patients were monitored for signs and symptoms of recurrent VAP. Incidence and risk factors for treatment failure, defined as pneumonia recurrence, were determined using univariate logistic regression analysis and receiver operating characteristic (ROC) curves. Forty-three patients met the inclusion criteria. The incidence of treatment failure among culture-negative VAP following early antibiotic discontinuation was 27.9% (12 patients). There were no significant differences in procalcitonin levels, leukocyte counts or body temperature between the two groups, except for the modified clinical pulmonary infection score (mCPIS) (5.42 ± 2.19 versus 3.9 ± 1.54, p = 0.014). Procalcitonin levels at VAP diagnosis and antibiotic cessation both showed low predictive capacity for treatment failure (AUC 0.56, CI 95% 0.36-0.76 and AUC 0.57, CI 95% 0.37-0.76, respectively). However, combining mCPIS with procalcitonin improved the predictive value for treatment failure (AUC 0.765, CI 95% 0.56-0.96). Early antibiotic discontinuation may lead to a high incidence of treatment failure among culture-negative VAP patients. Procalcitonin alone should not guide antibiotic discontinuation decisions while combining mCPIS and procalcitonin enhances predictive accuracy for treatment failure.

Nafcillin-induced thrombocytopenia: An uncommon complication

Drug-induced thrombocytopenia is a challenging clinical dilemma that is often overlooked. Nafcillin is a beta-lactam anti-staphylococcal penicillin antibiotic used as a first-line treatment for methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia and severe infections. Nafcillin has been associated with a higher rate of premature antibiotic discontinuation than cefazolin. Here we report a 58-year-old woman with multiple comorbid conditions who presented with a prosthetic right hip joint infection due to MSSA and was treated with nafcillin but developed profound thrombocytopenia due to a possible nafcillin side effect on the 14th day of therapy. Thrombocytopenia resolved after discontinuation of nafcillin, and the patient was treated successfully with cefazolin. Keywords: Nafcillin-induced thrombocytopenia, drug-induced thrombocytopenia, thrombocytopenia

Metagenomic Next-Generation Sequencing-Based Fine-Needle Aspiration in Patients With Suspected Infected Pancreatic Necrosis.

Fine-needle aspiration (FNA) is no longer recommended for diagnosing infected pancreatic necrosis (IPN) due to a high false-negative rate. Metagenomic next-generation sequencing (mNGS) is a valuable tool for identifying potential pathogens. We hypothesized that adding mNGS to the standard FNA procedure may increase diagnostic accuracy. This is a prospective, single-arm feasibility study enrolling patients with acute necrotizing pancreatitis complicated by suspected IPN. Computed tomography-guided FNA was performed immediately after enrollment, and the drainage samples were subjected to culture and mNGS assays simultaneously. Confirmatory IPN within the following week of the index FNA procedure was the reference standard. The diagnostic performance of FNA-mNGS and the impact of mNGS results on treatment were evaluated. Historical controls were used for comparison of clinical outcomes. There was no significant difference between mNGS and culture in the positive rate (75% vs 70%, P = 0.723). The accuracy of FNA-mNGS was 80.0%, with a sensitivity of 82.35%, specificity of 66.67%, positive predictive value of 93.3%, and negative predictive value of 40.0%. The results of the mNGS led to treatment change in 16 of 20 patients (80%), including implementing percutaneous catheter drainage (n = 7), expanding antibiotic coverage (n = 2), percutaneous catheter drainage and expanding coverage (n = 4), narrowing antibiotic coverage (n = 1), and discontinuation of antibiotics (n = 2). The FNA-mNGS approach was not associated with improved clinical outcomes compared with the historical control group. The addition of mNGS to standard FNA has comparable diagnostic accuracy with culture-based FNA and may not be associated with improved clinical outcomes.

Extended-Infusion β-Lactam Therapy, Mortality, and Subsequent Antibiotic Resistance Among Hospitalized Adults With Gram-Negative Bloodstream Infections

Current evidence is conflicting for associations of extended-infusion β-lactam (EI-BL) therapy with clinical outcomes. To investigate the association of EI-BL therapy with survival, adverse events, and emergence of antibiotic resistance in adults with gram-negative bloodstream infections (GN-BSI). This cohort study of consecutive adults with GN-BSI admitted to 24 United States hospitals between January 1, 2019, and December 31, 2019, receiving EI-BL were compared with adults with GN-BSI receiving the same agents as intermittent infusion β-lactam (II-BL; ≤1-hour infusions). Statistical analysis was performed from January to October 2023. EI-BL (ie, ≥3-hour infusion). EI-BL and II-BL groups underwent 1:3 nearest-neighbor propensity score matching (PSM) without replacement. Multivariable regression was applied to the PSM cohort to investigate outcomes, all censored at day 90. The primary outcome was mortality; secondary outcomes included antibiotic adverse events and emergence of resistance (≥4-fold increase in the minimum inhibitory concentration of the β-lactam used to treat the index GN-BSI). Among the 4861 patients included, 2547 (52.4%) were male; and the median (IQR) age was 67 (55-77) years. There were 352 patients in the EI-BL 1:3 PSM group, and 1056 patients in the II-BL 1:3 PSM group. Among 1408 PSM patients, 373 (26.5%) died by day 90. The odds of mortality were lower in the EI-BL group (adjusted odds ratio [aOR], 0.71 [95% CI, 0.52-0.97]). In a stratified analysis, a survival benefit was only identified in patients with severe illness or elevated minimum inhibitory concentrations (ie, in the intermediate range for the antibiotic administered). There were increased odds of catheter complications (aOR, 3.14 [95% CI, 1.66-5.96]) and antibiotic discontinuation because of adverse events (eg, acute kidney injury, cytopenias, seizures) in the EI-BL group (aOR, 3.66 [95% CI, 1.68-7.95]). Emergence of resistance was similar in the EI-BL and II-BL groups at 2.9% vs 7.2%, respectively (P = .35). In this cohort study of patients with GN-BSI, EI-BL therapy was associated with reduced mortality for patients with severe illness or those infected with nonsusceptible organisms; potential advantages in other groups remain unclear and need to be balanced with potential adverse events. The subsequent emergence of resistance warrants investigation in a larger cohort.

European society of clinical microbiology and infectious diseases guidelines for antimicrobial stewardship in emergency departments (endorsed by European association of hospital pharmacists)

ScopeThis European Society of Clinical Microbiology and Infectious Diseases guideline provides evidence-based recommendations to support a selection of appropriate antibiotic use practices for patients seen in the emergency department (ED) and guidance for their implementation. The topics addressed in this guideline are (a) Do biomarkers or rapid pathogen tests improve antibiotic prescribing and/or clinical outcomes? (b) Does taking blood cultures in common infectious syndromes improve antibiotic prescribing and/or clinical outcomes? (c) Does watchful waiting without antibacterial therapy or with delayed antibiotic prescribing reduce antibiotic prescribing without worsening clinical outcomes in patients with specific infectious syndromes? (d) Do structured culture follow-up programs in patients discharged from the ED with cultures pending improve antibiotic prescribing? MethodsAn expert panel was convened by European Society of Clinical Microbiology and Infectious Diseases and the guideline chair. The panel selected in consensus the four most relevant antimicrobial stewardship topics according to pre-defined relevance criteria. For each main question for the four topics, a systematic review was performed, including randomized controlled trials and observational studies. Both clinical outcomes and stewardship process outcomes related to antibiotic use were deemed relevant. The literature searches were conducted between May 2021 and March 2022. In April 2022, the panel members were formally asked to suggest additional studies that were not identified in the initial searches. Data were summarized in a meta-analysis if possible or otherwise summarized narratively. The certainty of the evidence was classified according to the Grading of Recommendations Assessment, Development and Evaluation criteria. The guideline panel reviewed the evidence per topic critically appraising the evidence and formulated recommendations through a consensus-based process. The strength of the recommendations was classified as strong or weak. To substantiate the implementation process, implementation trials or observational studies describing facilitators/barriers for implementation were identified from the same searches and were summarized narratively. RecommendationsThe recommendations on the use of biomarkers and rapid pathogen diagnostic tests focus on the initiation of antibiotics in patients admitted through the ED. Their effect on the discontinuation or de-escalation of antibiotics during hospital stay was not reported, neither was their effect on hospital infection prevention and control practices. The recommendations on watchful waiting (i.e. withholding antibiotics with some form of follow-up) focus on specific infectious syndromes for which the primary care literature was also included. The recommendations on blood cultures focus on the indication in three common infectious syndromes in the ED explicitly excluding patients with sepsis or septic shock. Most recommendations are based on very low and low certainty of evidence, leading to weak recommendations or, when no evidence was available, to best practice statements. Implementation of these recommendations needs to be adapted to the specific settings and circumstances of the ED. The scarcity of high-quality studies in the area of antimicrobial stewardship in the ED highlights the need for future research in this field.

Prospective antimicrobial stewardship interventions by multidisciplinary teams to reduce neonatal antibiotic use in South Africa: The Neonatal Antimicrobial Stewardship (NeoAMS) study

BackgroundHospitalized neonates are vulnerable to infection and have high rates of antibiotic utilization. MethodsFourteen South African neonatal units (seven public, seven private sector) assembled multidisciplinary teams involving neonatologists, microbiologists, pharmacists, and nurses to implement prospective audit and feedback neonatal antimicrobial stewardship (NeoAMS) interventions. The teams attended seven online training sessions. Pharmacists conducted weekday antibiotic prescription reviews in the neonatal intensive care unit and/or neonatal wards providing feedback to the clinical teams. Anonymized demographic and NeoAMS interventions data were aggregated for descriptive purposes and statistical analysis. FindingsDuring the 20-week NeoAMS intervention in 2022, 565 neonates were enrolled. Pharmacists evaluated seven hundred antibiotic prescription episodes; rule-out sepsis (180; 26%) and culture-negative sepsis (138; 20%) were the most frequent indications for antibiotic prescription. For infection episodes with an identified pathogen, only 51% (116/229) of empiric treatments provided adequate antimicrobial coverage. Pharmacists recommended 437 NeoAMS interventions (0·6 per antibiotic prescription episode), with antibiotic discontinuation (42%), therapeutic drug monitoring (17%), and dosing (15%) recommendations most frequent. Neonatal clinicians’ acceptance rates for AMS recommendations were high (338; 77%). Mean antibiotic length of therapy decreased by 24% from 9·1 to 6·9 days (0·1 day decrease per intervention week; P = 0·001), with the greatest decline in length of therapy for culture-negative sepsis (8·2 days (95% CI 5·7-11·7) to 5·9 days (95% CI 4·6-7·5); P = 0·032). InterpretationThis neonatal AMS programme was successfully implemented in heterogenous and resource-limited settings. Pharmacist-recommended AMS interventions had high rates of clinician acceptance. The NeoAMS intervention significantly reduced neonatal antibiotic use, particularly for culture-negative sepsis. FundingA grant from Merck provided partial support.

Follow-up of patients with urinary tract infections discharged from the emergency department: a mixed methods study.

To evaluate the quality of culture follow-up after emergency department (ED) discharge in patients with urinary tract infections (UTIs). This convergent mixed methods study included an observational cohort study and a qualitative interview study in UTI patients discharged from the ED of a Dutch university hospital. The primary outcomes of the observational study were the proportion of patients requiring adjustment of antibiotic therapy after culture review, and the proportion of patients in whom these adjustments were made. Logistic regression identified factors associated with these outcomes. Interviews assessed patient experiences and transcripts were analysed using inductive thematic content analysis. Integration of the results informed recommendations for high-quality follow-up. Out of 455 patients, 285 (63%) required culture-based treatment adjustments. In most patients, no adjustments were made (239/285, 84%). De-escalation was most frequently omitted (98%), followed by discontinuation of antibiotics (92%). A mean of 7.1 (SD 3.8) antibiotic days per patient could have been avoided in 103 patients. Patients with diabetes were less likely to require adjustments (aOR 0.50, 95%-CI 0.29-0.85). Patients with moderate or severe renal impairment (aOR 4.1, 95%-CI 1.45-11.33; aOR 4.2, 95%-CI 1.50-11.94) or recurrent UTIs (aOR 5.0, 95%-CI 2.27-11.18) were more likely to have received necessary adjustments. Twelve interviews also revealed varying degrees of follow-up. Three themes were identified: 'information and communication', 'coordination and accessibility of care' and 'individual needs and preferences'. Recommendations for high-quality follow-up advocate a person centred approach. This study highlights the importance of urine culture follow-up after ED discharge, mainly to reduce unnecessary antibiotic treatment, promote de-escalation and improve patient experience.

Serial neutrophils count as a stratifying tool for early follicular tonsilitis remission

Background/Aim: This study examines the correlation between sequential serum neutrophil levels and the overall improvement status or reduction rate of intravenous antibiotic administration. This study seeks to identify a cost-effective and easily accessible biomarker that can accurately predict the need for hospitalisation in patients with acute tonsillitis who are receiving intravenous broad-spectrum antibiotics. The goal is to determine the patients' suitability for early discontinuation of intravenous antibiotics and discharge. Methods: This study was conducted at the King Hussein Medical Centre in Jordan, focusing on patients with severe acute tonsillitis who did not respond to oral antibiotics. Data was collected from the electronic medical record system (Hakeem) from January 2018 to May 2021. The study classified serial serum neutrophil measurements during the first week of hospital admission into four categories. The levels were compared between the non-penicillin Cohort (Group I) and penicillin Cohort (Group II) using an Independent-T Test. The outcomes of interest included a drop in neutrophil counts exceeding 50%, a decrease in the use of intravenous antibiotics in favor of oral antibiotics, and early eligibility for discharge. The study also examined serial neutrophil counts over the tested days and compared to the outcomes of positive and negative states using receiver operating curve analyses. The optimal cutoff operating point for each ROC curve was determined by selecting the highest Youden's index of each prognosticator day level. The analysis of all results was conducted using SPSS version 20 with a significance level set at p-value <0.05. Results: This study analyzed 1638 adult and elderly patients admitted to KHMC, RMS, Amman, Jordan between January 2018 and May 2021. The average age was 51.88±16.22 years, with patients dependent on intravenous penicillin being slightly older. The distribution of males and females was significant, with males making up 2.55 times the number of females. The odds ratio for positive outcomes was 4.12, with a high rate of poor outcomes in 1318 out of all eligible patients. A total of 994 (60.7%) medical patients were treated with intravenous administration, while 644 (39.3%) surgical patients were scheduled for a tonsillectomy procedure. The risk estimate for patients admitted from medical wards compared to surgical wards was an odds ratio of 0.562. The study also provided sensitivity analysis for the four tested serial neutrophil prognosticators at different day levels. Conclusion: The study supports the use of Somatic Nucleated Cell (SNC) as a reliable measure for evaluating EFR in cases of catarrhal acute tonsillitis. The maximum SNC count in Group one was 11,269 cells per cubic millimeter. Acute streptococcal infection often exhibits an ESR higher than 40, but this may be concealed by other complications. The SNC test has advantages like simplicity, quickness, and cost-effectiveness, but lacks specificity. Monitoring SNC and EFR fluctuations can initiate treatment cessation, preventing relapse and severe complications during recovery.

Antibiotic use in infants at risk of early-onset sepsis: results from a unicentric retrospective cohort study

BackgroundAntibiotic use for early-onset sepsis represents a high percentage of antibiotic consumption in the neonatal setting. Measures to assess infants at risk of early-onset sepsis are needed to optimize antibiotic use. Our primary objective was to assess the impact of a departmental guideline on antibiotic use among term infants with suspected EOS not confirmed, in our neonatal unit.MethodsRetrospective cohort study, to compare antibiotic use in term infants during a baseline period of January to December 2018, and a postintervention period from October 2019, to September 2020, respectively. The primary outcome was antibiotic use measured by days of therapy, the antibiotic spectrum index, the antibiotic use rate, and the length of therapy.ResultsWe included 71 infants in the baseline period and 66 infants in the postintervention period. Compared to those in the baseline period, there was a significant reduction in overall antibiotic measures in the postintervention period, (P < 0.001). The total days of therapy/1000 patient-days decreased from 63/1000 patient-days during the baseline period to 25.8/1000 patient-days in the postintervention period, representing a relative reduction of 59%. The antibiotic use rate decreased by more than half of the infants, from 3.2% during the baseline period to 1.3% in the postintervention period.ConclusionsThe use of a departmental guideline to assess infants at risk of early-onset sepsis based on their clinical condition and prompt discontinuation of antibiotics, is a simple and low-cost measure that contributed to an important decrease in antibiotic use.

Perioperative Cefazolin for Total Joint Arthroplasty Patients Who Have a Penicillin Allergy: Is It Safe?

BackgroundCefazolin is the standard of care for perioperative antibiotic prophylaxis in total joint arthroplasty (TJA) in the United States. The potential allergic cross-reactivity between cefazolin and penicillin causes uncertainty regarding optimal antibiotic choice in patients who have a reported penicillin allergy (rPCNA). The purpose of this study was to determine the safety of perioperative cefazolin in PCNA patients undergoing primary TJA. MethodsWe identified all patients (n = 49,842) undergoing primary total hip arthroplasty (n = 25,659) or total knee arthroplasty (n = 24,183) from 2016 to 2022 who received perioperative intravenous antibiotic prophylaxis. Patients who had an rPCNA (n = 5,508) who received cefazolin (n = 4,938, 89.7%) were compared to rPCNA patients who did not (n = 570, 10.3%), and to patients who did not have an rPCNA (n = 43,359). The primary outcome was the rate of allergic reactions within 72 hours postoperatively. Secondary outcomes included the rates of superficial infections, deep infections, and Clostridioides difficile infections within 90 days. ResultsThe rate of allergic reactions was 0.1% (n = 5) in rPCNA patients who received cefazolin, compared to 0.2% (n = 1) in rPCNA patients who did not (P = .48) and 0.02% (n = 11) in patients who have no rPCNA (P = .02). Allergic reactions were mild in all 5 rPCNA patients who received cefazolin and were characterized by cutaneous symptoms (n = 4) or dyspnea in the absence of respiratory distress (n = 1) that resolved promptly with antibiotic discontinuation and administration of antihistamines and/or corticosteroids. We observed no differences in the rates of superficial infections (0.1 versus 0.2%, P = .58), deep infections (0.3 versus 0.4%, P = .68), or C difficile infections (0.04% versus 0%, P = .99) within 90 days in rPCNA patients who received cefazolin versus alternative perioperative antibiotics. ConclusionsIn this series of more than 5,500 patients who had an rPCNA undergoing primary TJA, perioperative prophylaxis with cefazolin resulted in a 0.1% incidence of allergic reactions that were clinically indolent. Cefazolin can be safely administered to most patients, independent of rPCNA severity. Level of EvidenceIII.

Diagnostic and antibiotic use practices among COVID-19 and non-COVID-19 patients in the Indonesian National Referral Hospital.

Little is known about diagnostic and antibiotic use practices in low and middle-income countries (LMICs) before and during COVID-19 pandemic. This information is crucial for monitoring and evaluation of diagnostic and antimicrobial stewardships in healthcare facilities. We linked and analyzed routine databases of hospital admission, microbiology laboratory and drug dispensing of Indonesian National Referral Hospital from 2019 to 2020. Patients were classified as COVID-19 cases if their SARS-CoV-2 RT-PCR result were positive. Blood culture (BC) practices and time to discontinuation of parenteral antibiotics among inpatients who received a parenteral antibiotic for at least four consecutive days were used to assess diagnostic and antibiotic use practices, respectively. Fine and Grey subdistribution hazard model was used. Of 1,311 COVID-19 and 58,917 non-COVID-19 inpatients, 333 (25.4%) and 18,837 (32.0%) received a parenteral antibiotic for at least four consecutive days. Proportion of patients having BC taken within ±1 calendar day of parenteral antibiotics being started was higher in COVID-19 than in non-COVID-19 patients (21.0% [70/333] vs. 18.7% [3,529/18,837]; p<0.001). Cumulative incidence of having a BC taken within 28 days was higher in COVID-19 than in non-COVID-19 patients (44.7% [149/333] vs. 33.2% [6,254/18,837]; adjusted subdistribution-hazard ratio [aSHR] 1.71, 95% confidence interval [CI] 1.47-1.99, p<0.001). The median time to discontinuation of parenteral antibiotics was longer in COVID-19 than in non-COVID-19 patients (13 days vs. 8 days; aSHR 0.73, 95%Cl 0.65-0.83, p<0.001). Routine electronic data could be used to inform diagnostic and antibiotic use practices in LMICs. In Indonesia, the proportion of timely blood culture is low in both COVID-19 and non-COVID-19 patients, and duration of parenteral antibiotics is longer in COVID-19 patients. Improving diagnostic and antimicrobial stewardship is critically needed.

Early assessment of blood culture negativity as a potential support tool for antimicrobial stewardship

ObjectiveTo assess whether 48-h negative blood culture (BC) bottles are still negative at the classic 120-h incubation endpoint and whether 48 h might be the time to make antimicrobial therapy decisions. MethodsData from the first collected bottles from bloodstream infection (BSI) episodes of single patients were retrospectively analyzed. Probabilities of bottles being negative at the classic endpoint were calculated from 0 to 120 h of incubation. ResultsAmong BC-negative episodes (4018/4901 [82.0%]), most (2097/4018 (52.2%) occurred in medicine patients. At 48 h, probability was 100.0% (95% CI, 99.9–100.0) for all 4018 patients. Of these, 1244 (31.0%) patients remained on antibiotics until 120 h. Excluding 401 (32.2%) patients who received antibiotics for another (non-bloodstream) infection, 843 (67.8%) of 1244 patients could have merited early (48-h) discontinuation of antibiotics. Stopping treatment in these patients would have led to saving 5201 days of access (943 [18.1%] days), watch (3624 [69.7%] days), or reserve (634 [12.2%]) AWaRe groups’ antibiotics, which correspond to 65.6% (5201/7928) of days of administered antibiotics in all 1244 patients. ConclusionAs an early indicator of BC negativity, the 48-h endpoint could reliably support antimicrobial stewardship, but the clinical judgment remains imperative especially when BSI is highly suspected.

A prospective observational study on the efficacy of procalcitonin as a diagnostic test to exclude lower urinary tract infection and to minimize antibiotic overuse.

Urinary tract infection (UTI) stands out as the third-most common infection following gastrointestinal and respiratory tract infections. Over the past decade, the biomarker procalcitonin (PCT) has gained prominence to facilitate the detection of bacterial infections and reduce excessive antibiotic exposure. The objective of this study was to mitigate the overuse of antibiotics, by promoting the noninitiation or early discontinuation of empirical antibiotics, which would significantly help minimize the proliferation of multidrug-resistant bacteria. A prospective observational study was carried out at the tertiary care center in the Department of General Medicine of Kalinga Institute of Medical Sciences, Bhubaneswar, involving 200 patients with symptoms of lower UTI such as increased frequency, urgency, burning micturition, retention, and suprapubic tenderness with or without positive urinalysis. Detailed demographic profiles along with symptoms at the time of admission were recorded in a pretested structured format. To determine a positive diagnosis of UTI, signs and symptoms of UTI with or without urinary cultures were tested. The PCT level was estimated using enhanced chemiluminescence technique. Other routine tests such as complete blood count, renal function test, liver function test, urine routine microscopy, culture, chest X-ray, and ultrasonography abdomen pelvis were done and recorded. All patients, who had an initial serum PCT level of < 0.5 ng/mL, were kept under observation with only conservative and symptomatic treatments. Patients were further reviewed for improvement in symptoms and repeat urine microscopy. All patients, who had an initial serum PCT level of > 0.5 ng/mL, were initiated with antibiotics as per the culture and sensitivity reports. Patients were followed up for improvement in symptoms with reports of repeated urinalysis. Our study reported the fact that 9.5% of the patients with initial serum PCT ≥ 0.5 ng/mL showed no improvement in symptoms despite starting antibiotics while significantly higher number of symptomatic patients (60%) with initial serum PCT < 0.5 ng/ml showed improvement in symptoms with conservative treatment without antibiotics. A lower PCT level rules out bacterial invasion and thus can be used as a novel marker in antibiotic stewardship.

Adherence to stewardship recommendations for antibiotic discontinuation reduces antibiotic-associated adverse drug events.

Inappropriate antibiotic use may lead to increased adverse drug events (ADEs). This study assessed whether an antimicrobial stewardship recommendation to discontinue antibiotics in patients with low likelihood for bacterial infection reduced antibiotic duration and antibiotic-associated ADEs. At a 4-hospital system, hospitalized adult patients receiving empiric antibiotics for suspected infection were identified between May 2, 2016 and June 30, 2018. For those patients who were deemed unlikely to have a bacterial infection, a note was left by an infectious diseases physician recommending antibiotic discontinuation. Patient cases were considered "adherent" to recommendations if antibiotics were discontinued within 48 hours of the note and "non-adherent" to recommendations if antibiotics were continued beyond this. Duration of antibiotics and potential antibiotic-associated ADEs were collected retrospectively. Attribution of the adverse event to the antibiotic was decided upon by the investigators. The incidence of ADEs and duration of antibiotics between the adherent and non-adherent groups were compared. Of 253 patients deemed unlikely to have a bacterial infection, 114 (45%) treatment teams stopped antibiotics within 48 hours of the recommendation, and 139 (55%) continued antibiotics. The total number of ADEs was significantly higher in the non-adherent group compared to the adherent group (34 ADEs vs 9 ADEs, P = .001). The median number of total prescribed antibiotic days was higher in the non-adherent group than in the adherent group (5 days vs 1 day, P < .001). This study demonstrates that stewardship programs may prevent ADEs by recommending antibiotic discontinuation in patients with low suspicion for bacterial infection.

Clinical impact of multidisciplinary carbapenem stewardship interventions: a retrospective cohort study.

Antimicrobial stewardship (AMS) program aims to optimise antimicrobial utilisation and curb antimicrobial resistance. We investigated the clinical impact of AMS among patients with carbapenem in medical wards of a tertiary hospital. A retrospective cohort study was conducted on hospitalised adult patients treated with carbapenem and reviewed by a multidisciplinary AMS team. We compared the clinical outcomes of accepted (n = 103) and not-accepted AMS intervention cases (n = 37). The outcomes evaluated include trends of total white blood cells (TWBC), C-reactive protein (CRP), body temperature at day-7, and clinical status at day-30 post-AMS intervention. The interventions included discontinuation (50%), de-escalation (47.9%) and escalation (2.1%) of antibiotics, where the acceptance rate was 67.1%, 80.6% and 66.7%, respectively. Overall, we found no significant difference in clinical outcomes between accepted and not-accepted AMS interventions at day-7 and day-30 post-interventions. On day-7, 62.0% of patients in the accepted group showed decreased or normalised TWBC and CRP levels compared to 47.4% of the not-accepted group (p = 0.271). The mortality at day-30 (32% versus 35%, p = 0.73), discharge rate (53.4% versus 45.9%, p = 0.437), and median length of hospital stay (36.0 versus 30.0days, p = 0.526) between the groups were comparable. The predictors of 30-day mortality in the study subjects were Charlson Comorbidity Index > 3 (OR: 2.84, 95% CI 1.28-6.29, p = 0.010) and being febrile at day-7 (OR: 4.58, 95% CI 1.83-11.5, p = 0.001). AMS interventions do not result in significant adverse clinical impact and mortality risk.

Clinical and laboratory diagnostics of drug-induced liver injury by antibiotics

Liver damage in a patient can precede the prescribing of antibiotics for the treatment of an infectious disease, may occur during their use or after their discontinuation. Liver damage before the start of treatment limits the choice and affects the dosage of antimicrobial agents. The occurrence of liver damage during antimicrobial treatment or after discontinuation of antibiotics can be both a consequence of this intake and independent of treatment with antibacterial drugs. Diagnosis of such lesions requires the use of many clinical, laboratory and instrumental investigations. The key element of diagnosis is the determination of the biochemical variant of liver damage, which makes it possible to plan the sequence of differential diagnosis. In case of suspicion of drug-induced damage to the liver, it is necessary to stop taking immediately the drugs that allegedly caused it. The next step is finding out the connection between the use of the antibiotic and the occurrence of the disease, taking into account the data of the literature regarding this possibility. Then it is necessary to estimate compatibility in time between the start of the use of drugs and the appearance of signs of liver damage, to assess the severity of the injury and, if possible, to prescribe appropriate medicines. There are several methods to assess causality between drugs and liver injury with RUCAM on the head. LiverTox is a well-known database on medicines, which are capable to cause liver damage. Antimicrobial agents belong to the most frequent causes of drug-induced liver injury. Most of such injuries are idiosyncratic. There was used a clinical example of possible drug-induced liver damage to illustrate decisions and difficulties in proving the etiological role of an antibiotic in a case, when liver damage arose during management of a patient with community-acquired pneumonia. This artic­le is a clinical lecture. Keywords: toxic action, biochemical variant, antimicrobials.

Ciprofloxacin Ophthalmic DRESS Syndrome: Case Report

Introduction: Drug rash with eosinophilia and systemic symptoms (DRESS syndrome), also known as drug-induced hypersensitivity syndrome, is a rare severe systemic hypersensitivity drug reaction. Diagnosing DRESS syndrome is challenging due to non-specific manifestations that can make it difficult to recognize. Therefore, addressing and discussing this issue is extremely important, considering the potential lethality of a treatable syndrome. Clinical case: We describe the clinical characteristics of a 39-year-old female who presented with DRESS syndrome associated with the use of ciprofloxacin ophthalmic. The patient manifested a mild maculopapular rash located in the pelvic limbs with subsequent ascending distribution and generalized erythematoviolaceous affecting four extremities, trunk, facial region and scalp, together with fever and lymphadenopathy. Paraclinical tests revealed leukocytosis and eosinophilia. According to RegiScar's ranking, it scored 6 points, classifying it as the definitive case for DRESS. He concluded a schedule with prednisone 1 mg/kg/day with a slow reduction dose, obtaining a good response to treatment. Conclusions: DRESS syndrome should be suspected in a patient receiving medical treatment who presents with the following signs and symptoms: rash, fever (38°C), facial edema, and lymphadenopathy. Fortunately, this reaction is usually reversible, with a low incidence of residual damage or mortality, in the case of timely discontinuation of antibiotics and use of topical or systemic corticosteroids.

Antibiotic-Associated Drug-Induced Liver Injury in Critically Ill Children: A Prospective Observational Study

Scientific relevance. Drug-induced liver injury (DILI) is associated, among other things, with the use of antibiotics. Children with DILI are at risk of acute liver failure and even death. However, the literature on the subject provides little information on the possibility of distinguishing the types of hepatic lesions to diagnose potentially life-threatening DILI in time.Aim. The study aimed to describe the phenotype of new-onset DILI associated with antibiotics in critically ill children with nosocomial infection.Materials and methods. The authors conducted a prospective observational study in the resuscitation and intensive care units of the Morozov Children’s City Clinical Hospital from 1 February 2020 to 1 September 2021. The study assessed the incidence of antibiotic-associated DILI using the Global Trigger Tool. The study enrolled 100 critically ill children with nosocomial infection aged 0 to 17 years (44 boys and 56 girls).Results. Signs of hepatotoxicity were detected in 19 patients, including 8 with abnormal liver function tests but normal liver function and 11 with abnormal liver function tests and clinically apparent liver disease. Thus, the incidence of new-onset hepatotoxicity associated with antibiotics amounted to 12.9 cases per 100,000 paediatric patients, and the incidence of DILI was 7.5 cases per 100,000 children. Based on the analysis of medical records, biochemical findings, and relationships between the time of dosing and the manifestation of signs of liver disorder in 11 children, the authors characterised the phenotype of idiosyncratic cholestatic hepatitis. Critically ill children treated with antibiotics showed alanine transaminase activity up to 10 times the upper limit of normal (ULN), bilirubin levels up to 4.45 times the ULN, and gamma-glutamyl transferase activity up to 5 times the ULN. The odds of developing new-onset DILI were the highest with tigecycline (OR: 4.07; 95% CI: 1.32–12.50) and meropenem (OR: 1.84; 95% CI: 1.01–3.36). In 6 patients, clinical signs of idiosyncratic cholestatic hepatitis resolved within a few weeks after antibiotic discontinuation. The other 5 patients with clinical signs of idiosyncratic cholestatic hepatitis died.Conclusions. The authors described the phenotype of idiosyncratic cholestatic liver injury associated with antibiotics in critically ill children. The role of pharmacogenetic markers in the development of DILI associated with antibiotics in critically ill children needs to be assessed further to implement a risk-based approach and mitigate the risks.

Treatment experience with continuous local antibiotic perfusion for periprosthetic joint infection

BackgroundAntibiotic concentrations 100–1000 times higher than the minimum inhibitory concentration are necessary for eradicating biofilms in periprosthetic joint infections (PJI). Achieving this with intravenous antibiotics is challenging, but continuous local antibiotic perfusion (CLAP) can increase the local concentration of antibiotics. Although there are several reports on CLAP therapy in the fracture-related infection, there are only few reports on its application in PJI. Here, we report our experience with CLAP therapy for PJI. MethodsEight patients with PJI (two males and six females, with mean age of 73.5 years [±11.6]) were treated at our department, and their clinical characteristics were analyzed. The parameters considered were the classification of PJI, surgical procedure, duration of CLAP, duration of transvenous antibiotic administration, time of CRP-negative status, whether the infection resolved or recurred, and whether there were complications due to CLAP. ResultsInitial surgery included total knee arthroplasty in five cases, unicompartmental knee arthroplasty in one case, and total hip arthroplasty in two cases. There were four cases of early postoperative infection, two of acute delayed infection, and two of chronic delayed infection. The surgical procedures performed were two-stage revision for two patients, and debridement, antibiotics, and implant retention (DAIR) for the other six. The mean durations of CLAP and transvenous antibiotic administration were 8.5 (±2.4) and 22.4 days (±13.7), respectively, and the mean time to CRP-negative status was 23.3 days (±10.7). All eight patients successfully resolved without additional irrigation or debridement, and no recurrence was observed at the last follow-up after discontinuation of oral antibiotics. No systemic side effects of gentamicin or other complications associated with CLAP were observed. ConclusionAll patients achieved infection resolution with the combined use of CLAP. This suggests that CLAP is a useful treatment option for PJI.

2763. Evaluating the Safety and Effectiveness of Long-term Antibiotic Suppression in Patients with Left Ventricular Assist Devices

Abstract Background The utilization of left ventricular assist devices (LVADs) as a bridge to transplantation or destination therapy for non-transplant candidates continues to rise. Unfortunately, infection remains one of the most common complication and lack of definitive source control often leads to the decision to initiate long-term antibiotic suppression. The purpose of this retrospective cohort study is to evaluate the long-term safety and effectiveness of antibiotic suppression following an LVAD-related or LVAD-specific infection. Methods Adults who underwent LVAD placement between August 2018 and September 2022 at Prisma Health Midlands and received antibiotic suppression for an LVAD-related or LVAD-specific infection were evaluated. Safety was evaluated as a composite endpoint of treatment emergent adverse events, and discontinuation of or decrease in dose due to tolerability concerns. Effectiveness was evaluated as the proportion of patients without a suppression emergent infection (SEI) within six months of antibiotic suppression initiation. Patients experiencing a SEI (failure) were compared to those without an SEI (success) at six months. Secondary outcomes included the proportion of patients experiencing early SEI within 90 days of antibiotic suppression initiation and evaluation of factors associated with success of antibiotic suppression at six months. Results Fifty-one patients received antibiotic suppressive therapy following an LVAD-related or LVAD-specific index infection. Patients were followed for a minimum of 6 months and an average 2.8 years. Treatment emergent adverse events occurred in 4 (7.8%) patients, with 2 events leading to antibiotic discontinuation. SEI occurred in 9 (17.6%) of patients at 6 months with the most common organisms being P. aeruginosa, S. aureus, and S. epidermidis. Early SEI was observed in 4 (7.8%) patients. Overall, SEI occurred in 28 patients (55%) at a median 341 days (IQR 157-502). Documented resistance to suppressive antibiotic was observed in 13 (25.4%) patients. Index infections with a gram-negative organism was significantly more common in those experiencing SEI (80% vs. 47%, p=0.031). Conclusion Antibiotic suppression following LVAD-associated infections is well-tolerated and successful in 82% of patients at 6 months. Disclosures Julie Ann Justo, PharmD, MS, FIDSA, BCPS, Gilead Sciences: Advisor/Consultant|Shionogi: Advisor/Consultant|Vaxart: Stocks/Bonds