In-hospital mortality among patients with invasive non-group A β-hemolytic Streptococcus treated with clindamycin combination therapy: a nationwide cohort study.

Clinical outcome comparison between adjunctive clindamycin vs. linezolid for invasive group A streptococcal infection.

Necrotizing soft tissue infection (NSTI) due to group A Streptococcus (GAS) is a severe life-threatening microbial infection. The administration of adjunct clindamycin has been recommended in the treatment of NSTIs due to GAS. However, robust evidence regarding the clinical benefits of adjunct clindamycin in NSTI patients remains controversial. We aimed to investigate the association between early administration of adjunct clindamycin and in-hospital mortality in patients with NSTI attributed to GAS. The present study was a nationwide retrospective cohort study, using the Japanese Diagnosis Procedure Combination inpatient database focusing on the period between 2010 and 2018. Data was extracted on patients diagnosed with NSTI due to GAS. We compared patients who were administered clindamycin on the day of admission (clindamycin group) with those who were not (control group). A propensity score overlap weighting method was adopted to adjust the unbalanced backgrounds. The primary endpoint was in-hospital mortality and survival at 90days after admission. We identified 404 eligible patients during the study period. After adjustment, patients in the clindamycin group were not significantly associated with reduced in-hospital mortality (19.2% vs. 17.5%; odds ratio, 1.11; 95% confidence interval, 0.59-2.09; p = 0.74) or improved survival at 90days after admission (hazard ratio, 0.92; 95% confidence interval, 0.51-1.68; p = 0.80). In this retrospective study, early adjunct clindamycin does not appear to improve survival. Therefore, the present study questions the benefits of clindamycin as an adjunct to broad spectrum antibiotics in patients with NSTI due to GAS.

Background Adjunctive clindamycin has survival benefit in invasive Group A streptococcus (GAS) infections. Like clindamycin, linezolid also leads to decreased toxin and virulence factor production. However, rising clindamycin resistance among GAS isolates and inadequate clinical data on linezolid both offer pause on which to choose. We examined the impact of adjunctive clindamycin vs. linezolid on survival among patients with GAS bloodstream infections (BSI) in the presence and absence of clindamycin resistant (clinda-R) isolates Methods Clinical characteristics, antimicrobial susceptibility testing (AST), and antibiotic therapy were examined for unique adult inpatient encounters with GAS BSIs in the PINC-AI Database. Patients treated with a β-lactam for ≥3 days ±3 days of culture who received clindamycin ±3 days of culture were overlap weighted on a propensity-score to those who received linezolid using basine patient and hospital factors. The primary outcome was odds ratio (OR) of in-hospital mortality associated with clindamycin (vs linezolid). The secondary outcome was length of stay (LOS) among survivors. Subgroups analyses were conducted excluding clindamycin receipients with clinda-R isolates (subgroup 1) and also missing clindamycin AST(including D-test; subgroup 2).Figure 1.Study Flow chart Selection of patients with Group A streptococcal blood stream infections. The database was queried for inpatients (aged ≥18 years) with blood culture displaying growth of Group A streptococcus, filtered on the basis of receiving β-lactam antibiotics within 3 days either side of culture sampling for a minimum duration of 3 days and received either adjunctive clindamycin or linezolid treatment within 3 days either side of culture sampling.Table 1:Baseline characteristics of all patients with Group A Streptococcal blood stream infections treated with β-lactam antibiotics and adjunctive clindamycin or linezolid (N=660)Abbreviations: IVIG: intravenous immunoglobulin, ICU: intensive care unit, IQR: interquartile range, SOFA: Sequential Organ Failure Assessment * This score was calculated by use of ICD-10-clinical modification codes and adapted from the methods used by Quan and colleagues ^ Calculated by use of an electronic health record-based adaption of the original Sequential Organ Failure Assessment ^^ Deteremined by clindamycin antimicrobial susceptibility and D-test results. Defined as resistant or intermediate clindamycin susceptibility results and/or a positive D-test result. † Defined as presence of ICD-10 codes coding for any of the following conditions: Human immunodeficiency virus, cancer, solid organ or hematopoietic stem cell transplantation, receipt of systemic corticosteroids, chemotherapy or other immunosuppressive therapy and immunodeficiency. ‡ Receipt of norepinephrine, epinephrine, phenylephrine, and dopamine administered within a 24-h period either side of culture sampling. Results Of 3019 β-lactam–treated inpatients with GAS BSI, 500 (17%) received clindamycin and 160 (5%) received linezolid. The prevalence of clinda-R isolates was 19%;1 isolate was linezolid resistant and excluded (Figure 1). Overlap weighting resulted in well balanced groups (Figure 2). In the overlap weighted cohort, mortality risk was similar between recipients of clindamycin (10%, [50/500]) vs linezolid (9%, [14/160]; OR 1.38 [95% CI: 0.76-2.49]). Among survivors median[interquartile range] LOS was similar between the two groups (8[9] vs. 9[8] days, p=0.45). Removing those with clinda-R isolates (N=84) and also missing AST (N=166) yielded similar results (Figure 3).Figure 2.Standardized mean differences for covariates included the propensity score calculation Standardized mean differences for covariates included in the propensity score generation averaged across exposure categories in the unweighted cohort (blue triangles) and overlap weighted cohort weight (red circles). After overlap weighting, the mean standard difference at each variable assessed was zero . Abbreviations: ICU: intensive care unit, IVIG: intravenous immunoglobulin, NSTI: necrotizing soft tissue infectionFigure 3.Odds Ratio of in-hospital mortality in patients with invasive group A streptococcal blood stream infection treated with adjunctive clindamycin versus adjunctive linezolid The ORs (95% CIs) of in-hospital mortality (including discharge to hospice) in the primary analysis and subgroup analysis with patients withclindamycin resistant isolates (subgroup 1) and those with clindamycin resistant isolates and missing clindamycin susceptibility results (subgroup 2) removed from clindamycin group. Abbreviations: CI: confidence interval Conclusion Among β-lactam-treated patients with GAS BSI, linezolid and clindamycin displayed comparable effectiveness as adjunctive antitoxin agents. Similar intrinsic effectiveness (i.e., in patients with only susceptible isolates) supports linezolid as an alternative even in low clinda-R settings. Disclosures Ahmed Babiker, MBBS, Roche: Advisor/Consultant Morgan Walker, MD, Cytovale: Advisor/Consultant

Retrospective cohort study of hospitalized adults treated with vancomycin or clindamycin for methicillin-resistant Staphylococcus aureus skin infections

Hemoptysis, a symptom common across various respiratory diseases, can cause airway obstruction leading to a life-threatening condition. Arterial embolization has been used to control bleeding from the lower airways. However, limited studies have evaluated its effects on in-hospital mortality in patients with hemoptysis requiring mechanical ventilation. The objective of this study was to clarify whether early intervention by arterial embolization reduced mortality in mechanically ventilated patients with hemoptysis. Retrospective cohort study from July 2010 to March 2017. More than 1,200 acute-care hospitals, comprising approximately 90% of all tertiary-care emergency hospitals in Japan. The study cohort was patients with pulmonary diseases hospitalized for hemoptysis and mechanically ventilated within 2 days of admission. We compared patients who had undergone arterial embolization within 3 days of endotracheal intubation (early embolization group) with patients who did not (control group). A total of 12,287 patients with hemoptysis requiring mechanical ventilation were analyzed. After 1:4 propensity score matching, there were 226 and 904 patients in the early embolization and control groups, respectively. The early embolization group was associated with lower 7-day and 30-day mortalities (7-d mortality: 1.3% vs 4.0%; odds ratio, 0.39; 95% CI, 0.16-0.97; p = 0.044 and 30-d mortality: 7.5% vs 16.8%; odds ratio, 0.45; 95% CI, 0.28-0.73; p = 0.001) and shorter duration of mechanical ventilation (median 6 d, interquartile range 4-13 d vs 8 d, interquartile range 4-19 d; p = 0.003) compared with the control group. Our results show that early intervention by arterial embolization may be effective in reducing 7-day and 30-day mortalities in patients with life-threatening hemoptysis requiring mechanical ventilation.

Atrial natriuretic peptide therapy and in-hospital mortality in acute myocardial infarction patients undergoing percutaneous coronary intervention

Adjunctive linezolid versus clindamycin for toxin inhibition in β-lactam-treated patients with invasive group A streptococcal infections in 195 US hospitals from 2016 to 2021: a retrospective cohort study with target trial emulation

Background Perioperative antibiotics reduce surgical site infections after hip and knee arthroplasty. Clindamycin is routinely used as a perioperative antibiotic in patients with beta-lactam allergy labels instead of first-line antibiotics like cefazolin. The purpose of this study is to assess the risk of adverse outcomes associated with the use of clindamycin to prevent surgical site infections (SSI) after total joint arthroplasty. Methods This retrospective review included adult patients labeled as allergic to penicillin or cephalosporin antibiotics, who underwent a primary total hip and/or knee arthroplasty between January 2020 through July 2021, and received perioperative antibiotics. The outcomes of SSI and Clostridioides difficile infection (CDI) within 90 days was compared between patients receiving perioperative clindamycin vs. non-clindamycin antibiotics. Results A total of 1,121 surgical procedures in 1,047 patients were included. The frequency of SSI for the cohort was 1.6% and CDI was 0.4%. SSI occurred more frequently in the clindamycin group than in the non-clindamycin group (4.3% vs 0.7%, p< .01). The average duration from surgery to SSI was 22.7 ± 11.6 days in the clindamycin group and 24.8 ± 11.1 days in the non-clindamycin group. The frequency of CDI occurrence was greater in the clindamycin group than the non-clindamycin group (1.1% vs. 0.1%, p=.05). The average duration from surgery to CDI was 32.6 + 26.6 days in the clindamycin group and 4.6 days in the non-clindamycin group. Multivariable logistic regression identified clindamycin-containing perioperative antibiotic regimens (odds ratio (OR) 5.5) and opioid use prior to surgery (OR 8.7) as risk factors for 90-day surgical site infection. Staphylococcus aureus was the cultured pathogen in 9 of the 17 SSIs. Conclusion This study found a significantly higher frequency of SSI and CDI when clindamycin-based regimens are used perioperatively for primary hip and knee arthroplasty. These results are likely related to decreased activity of clindamycin against Staphylococcus aureus and greater alterations of the microbiome in comparison to beta-lactams. Disclosures All Authors: No reported disclosures.

Microbiological analysis of autologous bone particles obtained by low-speed drilling and treated with different decontamination agents

Effectiveness of adjunctive clindamycin in β-lactam antibiotic-treated patients with invasive β-haemolytic streptococcal infections in US hospitals: a retrospective multicentre cohort study

The research was a randomized placebo-controlled clinical trial evaluating the use of clindamycin as a preoperative medication to prevent the dental implant. The purpose of the study was to assess if giving a single dose of 600 mg oral clindamycin 1 h before a conventional dental implant procedure could reduce the risk of early implant failure and post-surgical complications in healthy adults. A clinical trial was conducted with ethical standards, utilizing a randomized, double-blind, placebo-controlled approach. Healthy adults who required a single oral implant and had no previous surgical site infection or need for bone grafting were enrolled. Before surgery, participants were given either oral clindamycin or placebo at random. A single surgeon performed all operations, and patients were observed by a trained professional on multiple postoperative days. The study considered early dental implant failure as the loss or removal of an implant. Clinical, radiological, and surgical data were analyzed statistically to identify group differences. The number of subjects needed to treat, or harm, was calculated. The research involved two groups of 31 patients each: the control group and the clindamycin group. Two patients in the clindamycin group experienced implant failures (NNH = 15, p = 0.246). Three patients in the study had postoperative infections; two of them were from the placebo group, while one from the clindamycin group had an unsuccessful treatment outcome. The relative risk was 0.5, with a CI of 0.05-5.23 and an absolute risk reduction of 0.03. The confidence interval was -0.07-0.13, and the NNT was 31, with a CI of 7.2-∞ and p = 0.5. In addition, only one patient treated with clindamycin reported gastrointestinal disturbances and diarrhea. There is no conclusive evidence to suggest that administering clindamycin prior to oral implant surgery in healthy adults reduces the risk of implant failure or post-surgical complications.

BackgroundAlthough tranexamic acid is widely used in patients with haemoptysis, whether it improves mortality has not been well investigated. The aim of this study was to evaluate the effect of tranexamic acid on in-hospital mortality among patients with haemoptysis.MethodsThis was a retrospective study using data from the Japanese Diagnosis Procedure Combination inpatient database. We identified all cases of emergency admission due to haemoptysis from July 2010 to March 2017. Patients were divided into two groups: a control group, and a tranexamic acid group (those who received tranexamic acid on the day of admission). The primary outcome was in-hospital mortality, with secondary outcomes of hospital stay length and total healthcare cost. The data were evaluated using a propensity score matching analysis.ResultsAmong 28,539 included patients, 17,049 patients received tranexamic acid and 11,490 patients did not. Propensity score analysis generated 9933 matched pairs. Compared to the control group, patients in the tranexamic acid group had significantly lower in-hospital mortality (11.5% vs. 9.0%; risk difference, − 2.5%; 95% confidence interval (CI), − 3.5 to − 1.6%), shorter hospital stays (18 ± 24 days vs. 16 ± 18 days; risk difference, − 2.4 days; 95% CI, − 3.1 to − 1.8 days), and lower total healthcare costs ($7573 ± 10,085 vs. $6757 ± 9127; risk difference, $− 816; 95% CI, $− 1109 to − 523).ConclusionsTranexamic acid may reduce in-hospital mortality among patients with haemoptysis requiring emergency admission.

PurposeThe study investigates whether adding clindamycin to neurosurgery patients’ as a postsurgical management regimen improves recovery, provides neuroprotection, and prevents neurological complications. Neuron-specific enolase (NSE) and neurotensin (NT) were measured as biomarkers of inflammation, brain damage, and neuronal apoptosis.MethodsPatients were randomly assigned into two groups (n = 22 each) to receive the standard management plus either ceftriaxone (2 g / 12 h) or plus ceftriaxone and clindamycin (900 mg/8 h) as a combination therapy for seven days.ResultsNSE serum levels in the clindamycin and control group on day 3 were (10.01 ± 1.64) versus (23.77 ± 11.75), respectively (p = 0.0001). NT serum levels in the clindamycin and control groups on day 3 were (4.5 ± 2.8) versus (8.29 ± 7.97), respectively (p = 0.0418). Glasgow Coma Scale (GCS) on day 3 was (14.32 ± 1.13) versus (14.23 ± 1.31) in the clindamycin and the control groups, respectively, (p = 0.724). SOFA score assessed on day 3 (5 (22.7%)) and (1 (4.5%)) had grade 1, (15 (68.25)) and (14 (63.35)) had grade 2, (1 (4.5%)) and (5 (22.7%)) had grade 3, (0 (0.0%)) and (1 (4.5%)) had grade 4, and (1 (4.5%)) and (1 (4.5%)) had grade 5 in the clindamycin and control groups, respectively.ConclusionAdjunctive use of clindamycin might be a novel option that reduces secondary neurological injury/damage after neurosurgeries. Further and more extensive clinical trials are warranted to confirm the findings.

Acne vulgaris is a multifactorial disorder which is ideally treated with combination therapy with topical retinoids and antibiotics. The present study was conducted to compare the efficacy and safety of tazarotene plus clindamycin against adapalene plus clindamycin in facial acne vulgaris. This study is a randomized, open-label, parallel design clinical trial conducted on 60 patients with facial acne at the outpatient dermatology department in a tertiary healthcare center. The main outcome measures were change in the acne lesion count, Investigator's Static Global Assessment (ISGA) score, Global Acne Grading System (GAGS) score, and Acne-Specific Quality of Life Questionnaire (Acne-QoL) at the end of 4weeks of therapy. After randomization one group (n=30) received tazarotene 0.1% plus clindamycin 1% gel and another group (n=30) received adapalene 0.1% plus clindamycin 1% gel for 1 month. At follow-up, all the parameter were reassessed. In both treatment regimens the total number of facial acne lesions decreased significantly. The difference in the change in the total count between the two combination regimens was also significant [6.51, 95% confidence interval (CI) 1.91-11.09, p=0.007]. A ≥50% reduction in the total lesion count from the baseline levels was achieved by 71% of patients in the tazarotene plus clindamycin group and 22% of patients in the adapalene plus clindamycin group (p=0.0012). The difference in the change of inflammatory (p=0.017) and non-inflammatory (p=0.039) lesion counts in the tazarotene plus clindamycin group were significantly higher than the adapalene plus clindamycin group. The difference in change of the GAGS score was also significantly higher in the tazarotene plus clindamycin group (p=0.003). The ISGA score improved in 17 patients in the tazarotene plus clindamycin group versusnine patients in the adapalene plus clindamycin group (p=0.04). The change of total quality-of-life score was found to be significantly (p=0.027) higher in the tazarotene plus clindamycin group. Both treatment regimens were efficacious, but tazarotene plus clindamycin was found to be superior to adapalene plus clindamycin. The tolerability profile of both regimens was comparable. ClinicalTrials.gov Identifier: NCT02721173.

Rationale: Extracorporeal membrane oxygenation (ECMO) treatment is widely used worldwide, and many hospitals consider using antibiotics to prevent nosocomial infection in patients receiving ECMO treatment. However, the efficacy of antimicrobial prophylaxis for patients receiving ECMO treatment remains unclear. Objectives: To evaluate the efficacy of prophylactic antibiotics for patients receiving ECMO treatment. Methods: This retrospective cohort study was performed using data recorded in the Japanese Diagnosis Procedure Combination database from July 1, 2010, to March 31, 2017. We compared in-hospital mortality, nosocomial pneumonia, acute kidney injury, and diarrhea between patients receiving prophylactic antibiotics (prophylaxis group) and those not receiving antibiotics (control group) using propensity score matching. For in-hospital mortality and nosocomial pneumonia, multivariable logistic regression models fitted using a generalized estimating equation, stabilized inverse probability of treatment weighting, and instrumental variable analysis were performed. Results: We identified 9,615 eligible patients and classified them into the prophylaxis (n = 5,552) and control (n = 4,063) groups. In the propensity score-matched analysis, 3,650 pairs were generated. Significant differences between the prophylaxis group and the control group were detected in the in-hospital mortality (56.4% vs. 59.8%; risk difference, -3.7%; 95% confidence interval [CI], -6.0 to -1.3) and nosocomial pneumonia (12.9% vs. 15.3%; risk difference, -2.4%; 95% CI: -4.3 to -0.6). In the multivariable logistic regression models fitted using a generalized estimating equation, stabilized inverse probability of treatment weighting, and instrumental variable analysis, the point estimates suggested a direction similar to that found in the propensity score analysis. The proportions of patients with acute kidney injury or diarrhea did not significantly increase with the use of prophylactic antibiotics. Conclusions: Using prophylactic antibiotics during ECMO treatment was associated with reduced in-hospital mortality and lower proportions of patients with nosocomial pneumonia. Future prospective studies are needed to validate these results.