Kamal M.F. Itani

Linezolid versus Vancomycin in Treatment of Complicated Skin and Soft Tissue Infections

ABSTRACT Skin and soft tissue infections (SSTIs) are a common cause of morbidity in both the community and the hospital. An SSTI is classified as complicated if the infection has spread to the deeper soft tissues, if surgical intervention is necessary, or if the patient has a comorbid condition hindering treatment response (e.g., diabetes mellitus or human immunodeficiency virus). The purpose of this study was to compare linezolid to vancomycin in the treatment of suspected or proven methicillin-resistant gram-positive complicated SSTIs (CSSTIs) requiring hospitalization. This was a randomized, open-label, comparator-controlled, multicenter, multinational study that included patients with suspected or proven methicillin-resistant Staphylococcus aureus (MRSA) infections that involved substantial areas of skin or deeper soft tissues, such as cellulitis, abscesses, infected ulcers, or burns (<10% of total body surface area). Patients were randomized (1:1) to receive linezolid (600 mg) every 12 h either intravenously (i.v.) or orally or vancomycin (1 g) every 12 h i.v. In the intent-to-treat population, 92.2% and 88.5% of patients treated with linezolid and vancomycin, respectively, were clinically cured at the test-of-cure (TOC) visit (P = 0.057). Linezolid outcomes (124/140 patients or 88.6%) were superior to vancomycin outcomes (97/145 patients or 66.9%) at the TOC visit for patients with MRSA infections (P < 0.001). Drug-related adverse events were reported in similar numbers in both the linezolid and the vancomycin arms of the trial. The results of this study demonstrate that linezolid therapy is well tolerated, equivalent to vancomycin in treating CSSTIs, and superior to vancomycin in the treatment of CSSTIs due to MRSA.

Treating Foot Infections in Diabetic Patients: A Randomized, Multicenter, Open-Label Trial of Linezolid versus Ampicillin-Sulbactam/Amoxicillin-Clavulanate

Foot infections in diabetic patients are predominantly caused by gram-positive cocci, many of which are now antibiotic resistant. Because linezolid is active against these pathogens, we compared the efficacy and safety of intravenous and oral formulations with that of intravenous ampicillin-sulbactam and intravenous and oral amoxicillin-clavulanate given for 7-28 days in a randomized, open-label, multicenter study of all types of foot infection in diabetic patients (ratio of linezolid to comparator drug recipients, 2:1). Among 371 patients, the clinical cure rates associated with linezolid and the comparators were statistically equivalent overall (81% vs. 71%, respectively) but were significantly higher for linezolid-treated patients with infected foot ulcers (81% vs. 68%; P=.018) and for patients without osteomyelitis (87% vs. 72%; P=.003). Cure rates were comparable for inpatients and outpatients and for both oral and intravenous formulations. Drug-related adverse events were significantly more common in the linezolid group, but they were generally mild and reversible. Linezolid was at least as effective as aminopenicillin/beta-lactamase inhibitors for treating foot infections in diabetic patients.

Surgical Site Infection Prevention: The Importance of Operative Duration and Blood Transfusion—Results of the First American College of Surgeons–National Surgical Quality Improvement Program Best Practices Initiative

BACKGROUND Surgical site infections (SSI) continue to be a significant problem in surgery. The American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) Best Practices Initiative compared process and structural characteristics among 117 private sector hospitals in an effort to define best practices aimed at preventing SSI. STUDY DESIGN Using standard NSQIP methodologies, we identified 20 low outlier and 13 high outlier hospitals for SSI using data from the ACS-NSQIP in 2006. Each hospital was administered a process of care survey, and site visits were conducted to five hospitals. Comparisons between the low and high outlier hospitals were made with regard to patient characteristics, operative variables, structural variables, and processes of care. RESULT Hospitals that were high outliers for SSI had higher trainee-to-bed ratios (0.61 versus 0.25, p < 0.0001), and the operations took significantly longer (128.3+/-104.3 minutes versus 102.7+/-83.9 minutes, p < 0.001). Patients operated on at low outlier hospitals were less likely to present to the operating room anemic (4.9% versus 9.7%, p=0.007) or to receive a transfusion (5.1% versus 8.0%, p=0.03). In general, perioperative policies and practices were very similar between the low and high outlier hospitals, although low outlier hospitals were readily identified by site visitors. Overall, low outlier hospitals were smaller, efficient in the delivery of care, and experienced little operative staff turnover. CONCLUSIONS Our findings suggest that evidence-based SSI prevention practices do not easily distinguish well from poorly performing hospitals. But structural and process of care characteristics of hospitals were found to have a significant association with good results.

Centers for Disease Control and Prevention Guideline for the Prevention of Surgical Site Infection, 2017

Importance The human and financial costs of treating surgical site infections (SSIs) are increasing. The number of surgical procedures performed in the United States continues to rise, and surgical patients are initially seen with increasingly complex comorbidities. It is estimated that approximately half of SSIs are deemed preventable using evidence-based strategies. Objective To provide new and updated evidence-based recommendations for the prevention of SSI. Evidence Review A targeted systematic review of the literature was conducted in MEDLINE, EMBASE, CINAHL, and the Cochrane Library from 1998 through April 2014. A modified Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach was used to assess the quality of evidence and the strength of the resulting recommendation and to provide explicit links between them. Of 5759 titles and abstracts screened, 896 underwent full-text review by 2 independent reviewers. After exclusions, 170 studies were extracted into evidence tables, appraised, and synthesized. Findings Before surgery, patients should shower or bathe (full body) with soap (antimicrobial or nonantimicrobial) or an antiseptic agent on at least the night before the operative day. Antimicrobial prophylaxis should be administered only when indicated based on published clinical practice guidelines and timed such that a bactericidal concentration of the agents is established in the serum and tissues when the incision is made. In cesarean section procedures, antimicrobial prophylaxis should be administered before skin incision. Skin preparation in the operating room should be performed using an alcohol-based agent unless contraindicated. For clean and clean-contaminated procedures, additional prophylactic antimicrobial agent doses should not be administered after the surgical incision is closed in the operating room, even in the presence of a drain. Topical antimicrobial agents should not be applied to the surgical incision. During surgery, glycemic control should be implemented using blood glucose target levels less than 200 mg/dL, and normothermia should be maintained in all patients. Increased fraction of inspired oxygen should be administered during surgery and after extubation in the immediate postoperative period for patients with normal pulmonary function undergoing general anesthesia with endotracheal intubation. Transfusion of blood products should not be withheld from surgical patients as a means to prevent SSI. Conclusions and Relevance This guideline is intended to provide new and updated evidence-based recommendations for the prevention of SSI and should be incorporated into comprehensive surgical quality improvement programs to improve patient safety.

Comparison of Laparoscopic and Open Repair With Mesh for the Treatment of Ventral Incisional Hernia A Randomized Trial

BACKGROUND Laparoscopic repair of ventral incisional hernias has not been proved to be safer than open mesh repair. DESIGN Prospective randomized trial conducted between February 1, 2004, to January 31, 2007. SETTING Four Veterans Affairs medical centers. PARTICIPANTS One hundred sixty-two patients with ventral incisional hernias. INTERVENTIONS Standardized laparoscopic or open repair. MAIN OUTCOME MEASURES Overall complication rates at 8 weeks and the odds of complications, adjusted for study site, body mass index, and hernia type. RESULTS Of the 162 randomized patients, 146 underwent surgery (73 open and 73 laparoscopic repairs). Complications were less common in the laparoscopic group (23 patients [31.5%]) compared with the open repair group (35 patients [47.9%]; adjusted odds ratio [AOR], 0.45; 95% confidence interval [CI], 0.22-0.91; P = .03). Surgical site infection through 8 weeks was less common in the laparoscopic group (5.6% vs 23.3%; AOR, 0.2; 95% CI, 0.1-0.6). The mean worst pain score in the laparoscopic group was 15.2 mm lower on a visual analog scale at 52 weeks (95% CI, 1.0-29.3; P = .04). Time to resume work activities was shorter for the laparoscopic group than for the open repair group (median, 23.0 days vs 28.5 days), with an adjusted hazard ratio of 0.54 (95% CI, 0.28-1.04; P = .06). Overall recurrence at 2 years was 12.5% in the laparoscopic group and 8.2% in the open repair group (AOR, 1.6; 95% CI, 0.5-4.7; adjusted P = .44). CONCLUSIONS Laparoscopic repair was associated with fewer, albeit more severe, complications and improved some patient-centered outcomes. Trial Registration clinicaltrials.gov Identifier: NCT00240188.

Pylorus-preserving pancreatoduodenectomy: a clinical and physiologic appraisal

Since 1978, 252 patients from different centers in the world have undergone pylorus-preserving pancreatoduodenectomy. Fifty-five per cent of the patients had malignant tumors in the region of the head of the pancreas. The overall operative mortality rate was 2.8%. Anastomotic leakage and fistulae occurred in 19% of the patients. Pancreatic, biliary, and enteric fistulae represented 11%, 4%, and 4%, respectively. Peptic ulcers were subsequently diagnosed in seven patients (3%), two of whom required vagotomy and antrectomy. Delayed recovery of gastric function was the most common complication of this operation, with an overall incidence of 30%. Although the cause of this gastric dysfunction is unknown, its transient nature in most patients makes expectant therapy with gastric tube drainage the best remedy when the problem is encountered. Pylorus-preserving pancreatoduodenectomy decreased the incidence of postgastric surgery syndromes that are commonly associated with the standard Whipple operation. The existing data support the continued use of the operation and the need for future laboratory and clinical investigation of its physiologic impact.

Splenectomy for primary and recurrent immune thrombocytopenic purpura (ITP). Current criteria for patient selection and results.

Of 565 patients with thrombocytopenia admitted to Duke University Hospital between 1975 and 1985, 100 had splenectomy. Ninety-eight patients had failed chronic immunosuppressive therapy and three patients had acute intracranial bleeding or total absence of platelets in the peripheral blood smear, and had urgent splenectomy. At primary splenectomy, accessory spleens were identified and resected in 18% of patients. There was no operative mortality. Fifty-eight patients had an excellent response to splenectomy and their steroids were tapered off within 3 weeks. Thirteen patients had a poor response to primary splenectomy of whom eight remitted spontaneously and five required accessory splenectomy resulting in complete remission in three patients. Twenty-nine patients were considered nonresponders, 25 of whom had radionuclide scanning for accessory spleens. Seven of these patients had accessory spleens identified but only four consented to accessory splenectomy. In three of the four patients, a complete remission was achieved. Neither platelet antibody titers nor measurements of platelet survival or turnover predicted platelet response to splenectomy. However, immune thrombocytopenic purpura (ITP) in older patients was significantly less likely to respond to splencctomy. These data support continuing use of splenectomy in selected patients with ITP and an aggressive search for accessory spleens in patients who relapse since they are easily localized at operation by hand-held isotope detector probe.

Efficacy and safety of linezolid versus vancomycin for the treatment of complicated skin and soft-tissue infections proven to be caused by methicillin-resistant Staphylococcus aureus.

BACKGROUND This open-label study compared oral or intravenous linezolid with intravenous vancomycin for treatment of complicated skin and soft-tissue infections (cSSTIs) caused by methicillin-resistant Staphylococcus aureus (MRSA). METHODS Patients with proven MRSA cSSTI were randomized to receive linezolid or vancomycin. Clinical and microbiologic outcomes, duration of antimicrobial therapy, length of hospital stay, and safety were assessed. RESULTS In the per-protocol population, the rate of clinical success was similar in linezolid- and vancomycin-treated patients (P = .249). The rate of success was significantly higher in linezolid-treated patients in the modified intent-to-treat population (P = .048). The microbiologic success rate was higher for linezolid at the end of treatment (P < .001) and was similar at the end of the study (P = .127). Patients receiving linezolid had a significantly shorter length of stay and duration of intravenous therapy than patients receiving vancomycin. Both agents were well tolerated. Adverse events were similar to each drugs established safety profile. CONCLUSIONS Linezolid is an effective alternative to vancomycin for the treatment of cSSTI caused by MRSA.

Proficiency of Surgeons in Inguinal Hernia Repair Effect of Experience and Age

Objectives:We examined the influence of surgeon age and other factors on proficiency in laparoscopic or open hernia repair. Summary Background Data:In a multicenter, randomized trial comparing open and laparoscopic herniorrhaphies, conducted in Veterans Administration hospitals (CSP 456), we reported significant differences in recurrence rates (RR) for the laparoscopic procedure as a result of surgeons’ experience. We have also reported significant differences in RR for the open procedure related to resident postgraduate year (PGY) level. Methods:We analyzed data from unilateral laparoscopic and open herniorrhaphies from CSP 456 (n = 1629). Surgeons experience (experienced ≥250 procedures; inexperienced <250), surgeons age, median PGY level of the participating resident, operation time, and hospital observed-to-expected (O/E) ratios for mortality were potential independent predictors of RR. Results:Age was dichotomized into older (≥45 years) and younger (<45 years). Surgeons inexperience and older age were significant predictors of recurrence in laparoscopic herniorrhaphy. The odds of recurrence for an inexperienced surgeon aged 45 years or older was 1.72 times that of a younger inexperienced surgeon. For open repairs, although surgeons age and operation time appeared to be related to recurrence, only median PGY level of <3 was a significant independent predictor. Conclusion:This analysis demonstrates that surgeons age of 45 years and older, when combined with inexperience in laparoscopic inguinal herniorrhaphies, increases risk of recurrence. For open repairs, only a median PGY level of <3 was a significant risk factor.

Timing of Surgical Antibiotic Prophylaxis and the Risk of Surgical Site Infection

IMPORTANCE Timing of prophylactic antibiotic administration for surgical procedures is a nationally mandated and publicly reported quality metric sponsored by the Centers for Medicare and Medicaid Services Surgical Care Improvement Project. Numerous studies have failed to demonstrate that adherence to the Surgical Care Improvement Project prophylactic antibiotic timely administration measure is associated with decreased surgical site infection (SSI). OBJECTIVE; To determine whether prophylactic antibiotic timing is associated with SSI occurrence. DESIGN Retrospective cohort study using national Veterans Affairs patient-level data on prophylactic antibiotic timing for orthopedic, colorectal, vascular, and gynecologic procedures from 2005 through 2009. SETTING National Veterans Affairs Surgical Care Improvement Project data from 112 Veterans Affairs hospitals and matched Veterans Affairs Surgical Quality Improvement Program data. PATIENTS Patients undergoing hip or knee arthroplasty, colorectal surgical procedures, arterial vascular surgical procedures, and hysterectomy. INTERVENTION Timing of prophylactic antibiotic administration with respect to surgical incision time. MAIN OUTCOMES AND MEASURES Data for prophylactic antibiotic agent, prophylactic antibiotic timing with respect to surgical incision, and patient and procedure risk variables were assessed for their relationship with the occurrence of a composite superficial or deep incisional SSI within 30 days after the procedure. Nonlinear generalized additive models were used to examine the association between antibiotic timing and SSI. RESULTS Of the 32,459 operations, prophylactic antibiotics were administered at a median of 28 minutes (interquartile range, 17-39 minutes) prior to surgical incision, and 1497 cases (4.6%) developed an SSI. Compared with procedures with antibiotic administration within 60 minutes prior to incision, higher SSI rates were observed for timing more than 60 minutes prior to incision (unadjusted odds ratio [OR] = 1.34; 95% CI, 1.08-1.66) but not after incision (unadjusted OR = 1.26; 95% CI, 0.92-1.72). In unadjusted generalized additive models, we observed a significant nonlinear relationship between prophylactic antibiotic timing and SSI when considering timing as a continuous variable (P = .01). In generalized additive models adjusted for patient, procedure, and antibiotic variables, no significant association between prophylactic antibiotic timing and SSI was observed. Vancomycin hydrochloride was associated with higher SSI occurrence for orthopedic procedures (adjusted OR = 1.75; 95% CI, 1.16-2.65). Cefazolin sodium and quinolone in combination with an anaerobic agent were associated with fewer SSI events (cefazolin: adjusted OR = 0.49; 95% CI, 0.34-0.71; quinolone: adjusted OR = 0.55; 95% CI, 0.35-0.87) for colorectal procedures. CONCLUSIONS AND RELEVANCE The SSI risk varies by patient and procedure factors as well as antibiotic properties but is not significantly associated with prophylactic antibiotic timing. While adherence to the timely prophylactic antibiotic measure is not bad care, there is little evidence to suggest that it is better care.