Meta-analysis of the potential economic impact following introduction of absorbable antimicrobial sutures.

BACKGROUND: Despite several randomized trials, systematic reviews and meta-analyses that have demonstrated the effectiveness of antimicrobial (triclosan-coated or -impregnated) sutures (TCS), the clinical and economic impact of using these sutures compared with conventional non-antimicrobial-coated absorbable sutures (NCS) remains poorly documented. METHODS: An independent systematic review and meta-analysis of all published evidence from January 2005 to September 2016 comparing TCS with NCS was conducted. Surgical-site infection (SSI) was the primary outcome. The results of the meta-analysis were used in a decision-tree deterministic and stochastic cost model, using the National Health Service (NHS England)-based cost of inpatient admissions for infections and differential costs of TCS versus NCS. RESULTS: Thirty-four studies were included in the final assessment from an initial 163 identified citations; 20 of 34 studies were randomized, and 17 of 34 reported blinding of physicians and assessors. Using a random-effects model, the odds ratio for SSI in the TCS compared with NCS control groups was statistically significant (odds ratio 0·61, 95 per cent c.i. 0·52 to 0·73; P < 0·001). There was significant heterogeneity (I2 = 49 per cent). Using random-effects event estimates of SSI for TCS and NCS for each individual wound type, the mean savings per surgical procedure from using antimicrobial sutures were significant: £91·25 (90 per cent c.i. 49·62 to 142·76) (€105·09 (57·15 to 164·41); exchange rate 15 November 2016) across all wound types. CONCLUSION: The reviewed literature suggested that antimicrobial sutures may result in significant savings across various surgical wound types.

A narrative review of microbial biofilm in postoperative surgical site infections: clinical presentation and treatment.

OBJECTIVE: The global impact of surgical site infections (SSIs) on health-care systems is considerable: many are related to the formation of a microbial biofilm. Biofilm plays a significant role in the pathogenesis of implantable device-related infections and are also important in persistent postoperative skin and soft tissue wound infections. METHOD: PubMed and OVID databases were searched for relevant articles regarding biofilm-associated infection in surgery, including epidemiology, diagnosis, treatment and management. RESULTS: Biofilm-associated infections increase the use of health-care resources, prolong length of stay, increase cost of antibiotic therapy, result in additional surgical revisions and extend rehabilitation after discharge from health care. Staphylococcus aureus and Staphylococcus epidermidis are the most common isolates recovered from device-related infections. Early infection occurs within two weeks of implantation and is associated with intraoperative wound contamination; late-onset infections are often occult prolonging recognition by weeks, months and in some cases, years. Biofilm is a physical barrier against antibodies and granulocytic cell populations which may also impede the penetration of antibiotics. The ideal strategy for preventing biofilm-associated SSI is to prevent intraoperative contamination through compliance with effective surgical care bundles. Management of postoperative biofilm-associated infections involves surgical debridement followed by irrigation with antimicrobial agents and removal of infected devices, followed by insertion of antimicrobial adjuncts such as antimicrobial spacers, beads or sutures together with selective therapeutic agents that penetrate the mature biofilm. CONCLUSION: Biofilm-associated infections are a significant source of postoperative morbidity and mortality. Appropriate interventional strategies are warranted to reduce the risk of intraoperative contamination. DECLARATION OF INTEREST: The authors have no conflicts.

Approach to chronic wound infections.

Infection is the likeliest single cause of delayed healing in healing of chronic open wounds by secondary intention. If neglected it can progress from contamination to colonization and local infection through to systemic infection, sepsis and multiple organ dysfunction syndrome, and it can be life-threatening. Infection in chronic wounds is not as easy to define as in acute wounds, and is complicated by the presence of biofilms. There is, as yet, no diagnostic for biofilm presence, but it contributes to excessive inflammation - through excessive and prolonged stimulation of nitric oxide, inflammatory cytokines and free radicals - and activation of immune complexes and complement, leading to a delay in healing. Control of biofilm is a key part of chronic wound management. Maintenance debridement and use of topical antimicrobials (antiseptics) are more effective than antibiotics, which should be reserved for treating spreading local and systemic infection. The continuing rise of antimicrobial resistance to antibiotics should lead us to reserve their use for these indications, as no new effective antibiotics are in the research pipeline. Antiseptics are effective through many mechanisms of action, unlike antibiotics, which makes the development of resistance to them unlikely. There is little evidence to support the theoretical risk that antiseptics select resistant pathogens. However, the use of antiseptic dressings for preventing and managing biofilm and infection progression needs further research involving well-designed, randomized controlled trials.

Improving surgical site infection prevention in Asia-Pacific through appropriate surveillance programs: Challenges and recommendation.

BACKGROUND: Surgical site infections (SSIs) represent a substantial clinical and economic burden on patients and the healthcare system. The prevention of SSIs entails surveillance activities which lead to effective mitigation strategies, which are lacking across Asia Pacific (APAC). This manuscript aims to document gaps and challenges across APAC that affect the undertaking of a successful SSI surveillance activities and to provide recommendations on overcoming such challenges. METHODS: A targeted literature review with relevance to APAC identified a series of salient points pertaining to SSI prevention guidelines, implementation, surveillance and outcomes, which was discussed in July 2019 at the APAC Surgical Site Infection Prevention Symposium. An expert panel, comprising eight multidisciplinary experts from APAC and the USA, subsequently amalgamated the key discussion points from the Symposium and their clinical experiences in developing this article. RESULTS: The barriers to implementing a successful and effective APAC SSI surveillance program were identified as: (a) lack of standardized definitions, reporting methodology and accountability, (b) lack of fiscal resources, (c) reporting variability and under-reporting, and (d) lack of safety culture. Implementing an effective surveillance program in APAC will require countries to develop a well-designed and robust surveillance plan and ensure adequate training for staffs involved. CONCLUSION: To improve SSI prevention in the region, it is imperative to encourage implementation of national programs with standardized methodologies and accountabilities. An ongoing APAC information exchange, including data and methodologies, will enable continuous learning within the APAC region.

Coagulase-negative staphylococcal infections in vascular surgery: epidemiology and pathogenesis.

Staphylococcal infection of a vascular prosthesis is a relatively uncommon complication of peripheral vascular surgery; however, these infections and their sequelae can be catastrophic. The majority of prosthetic graft infections are caused by mucin-producing strains of Staphylococcus epidermidis, which express varying degrees of adherence to the synthetic substrates. Studies have demonstrated that the components and construction characteristics of the graft, implantation site, administration of antimicrobial agents, and endogenous microbial flora are all identifiable risk factors in vascular graft infections. Mucin production, a known virulence factor, has recently been shown to occur in endogenous coagulase-negative staphylococci (CNS) at the time of hospital admission. While mucin production plays an important role in the persistence of graft infections, there is no evidence that suggests a relationship between mucin and antimicrobial resistance. Identifying characteristics of (CNS) graft infections may include a draining wound sinus, poor graft incorporation, a perigraft exudate or a pseudoaneurysm at the anastomotic site. The occult nature of these infections, in which the patient is often asymptomatic, makes diagnosis and treatment difficult. The graft or graft exudate may be negative when routine culture methods are employed. The recognition of CNS graft infections requires a high index of suspicion and the treatment of these infections requires understanding of the pathogenic process, individualized surgical management, and the judicious use of antimicrobial agents.

Treatment of Hickman catheter sepsis using antibiotic lock technique.

Antibiotic lock therapy, an alternative treatment for Hickman catheter sepsis, was evaluated in six recipients of prolonged outpatient intravenous therapy. Twenty-two episodes of catheter sepsis were identified, involving coagulase-negative staphylococci (11), gram-negative bacilli (3), gram-positive bacilli (1), yeast (4), and mixed bacteria or fungi (3). In a select group of patients, treatment was successful 92% of the time.

The numbers game: sample-size determination.

Sample-size determination is a crucial component of study design. Estimates of sample size are influenced by the amount of change that must occur between study groups and the degree of risk that the investigator is willing to accept in evaluating the null hypothesis. A complete understanding of the impact of sample size on the interpretation of study data is therefore a prerequisite for quality, innovative, valid research.

Superior preservation of the staphylococcal glycocalyx with aldehyde-ruthenium red and select lysine salts using extended fixation times.

The utility of lysine-based aldehyde-ruthenium red fixatives for the preservation and/or staining of the fibrous staphylococcal glycocalyx was improved by substitution of alternative forms of lysine for the free amino form. Paraformaldehyde-glutaraldehyde fixatives containing alternative lysines, with or without ruthenium red, were compared at short 20-minute prefixation times and at extended overnight fixation times. Although inclusion of paraformaldehyde made longer fixation times possible, the length of time for "safe" fixation varied per sample and could not be predicted. All alternative lysine forms permitted fixation of at least 24 hours without sample loss. The L-lysine monohydrochloride or L-lysine acetate forms permitted longer fixation times than the L-lysine free amino form, and they had comparable or better preservation of the staphylococcal glycocalyx. Thus, the usefulness of aldehyde-lysine-based fixatives with minor changes has been enhanced.

Paraformaldehyde effect on ruthenium red and lysine preservation and staining of the staphylococcal glycocalyx.

The utility of lysine in glutaraldehyde-ruthenium red fixatives for the preservation and/or staining of the fibrous staphylococci glycocalyx was improved by inclusion of paraformaldehyde. Short, 20 min prefixation times for paraformaldehyde-glutaraldehyde fixatives containing lysine, with or without ruthenium red, were compared to an extended overnight fixation. Samples were often lost in fixatives that did not contain paraformaldehyde at extended fixation times hampering the effective use of these fixatives for clinical or environmental applications. Inclusion of paraformaldehyde in the fixation with lysine permitted longer fixation times as well as stabilized the staphylococcal glycocalyx. Thus, the technical usefulness of fixatives employing lysine was significantly improved.

Surgical sepsis: constancy of antibiotic susceptibility of causative organisms.

BACKGROUND: It is well documented that antibiotic therapy exerts selective pressure on bacteria. Conversion of bacteria from susceptible to resistant to antibiotics has been observed often during antimicrobial therapy. It has been postulated that human intestinal reservoirs facilitate communication of transposons that can transfer resistance determinants among various bacterial species. METHODS: This study examined the susceptibilities of organisms isolated from infected abdomens to a number of antibiotic agents during a 12-year time interval. Analysis included 1102 isolates recovered from 255 specimens, representing the following genera: Bacteroides, Clostridium, Gemella, Fusobacterium, Peptostreptococcus, Porphyromonas, Prevotella, Enterococcus, Staphylococcus, Streptococcus, Pseudomonas, and Enterobacteriaceae. Strains were tested against beta-lactam agents, beta-lactams in combination with beta-lactamase inhibitors, first, second, and third generation cephalosporins, aminoglycosides, clindamycin, metronidazole, chloramphenicol, and imipenem. RESULTS: The results indicated that during a time period of more than a decade essentially no change occurred in the antibiotic susceptible fraction of all species tested. CONCLUSIONS: Abdominal sepsis is caused by leakage of endogenous intestinal flora. This study suggests that the intestinal flora is not permanently affected by short-term antibiotic therapy and that older antibiotics are appropriate first-line therapeutic agents for community-acquired infections caused by normal intestinal flora.

Comparison of serum and tissue antibiotic levels in diabetes-related foot infections.

Parenteral antibiotics are used as an adjunct to amputation or operative debridement for patients with diabetes who require emergency surgery for a septic foot. In 26 patients with a diabetes-related foot infection, one dose of various intravenous antibiotic regimens (gentamicin and clindamycin, ticarcillin/clavulanate, ampicillin/sulbactam) was administered during the hour before the procedure, and assays were performed to measure the antibiotic serum and tissue levels at the time of surgical debridement. Aerobic and anaerobic cultures were performed on infected tissue. The 172 bacterial isolates, including 95 aerobes and 77 anaerobes, (6.6 isolates per patient) underwent antibiotic susceptibility testing. Antibiotic levels were calculated by biologic assay from serum and tissue biopsies from the viable margins of the surgical site, which subsequently healed primarily or supported a split-thickness skin graft. Sixteen of the patients achieved therapeutic serum levels, and therapeutic tissue levels were reached in six patients at the time of surgery. A significantly lower number of patients had therapeutic tissue levels compared to serum levels (p less than 0.01, chi square). Initial intravenous antibiotic administration provides inadequate tissue concentrations for treating foot infections in patients with diabetes. Adequate serum antibiotic levels do not reflect therapeutic tissue antibiotic levels at the surgical margins in this group of patients.

Adherence of mucin and non-mucin-producing staphylococci to preclotted and albumin-coated velour knitted vascular grafts.

The mechanisms involved in bacterial adherence to vascular grafts are important in understanding prosthetic infections. Albumin-coated Dacron (ACD) is a new development in vascular graft fabrication. However, albumin acts as a receptor for certain gram-positive bacterial adhesions. Five pathogenic, coagulase-negative Staphylococcus epidermidis strains were used to measure the differential microbial adherence to ACD versus untreated velour-knitted Dacron (VKD) vascular prostheses. Specimens of VKD, preclotted VKD, and ACD were inoculated with each of the five strains (10(7) colony-forming units/ml) for 2, 4, 8, 12, and 24 hours. After incubation, graft specimens were washed to remove nonadherent organisms and oscillated ultrasonically to remove adherent organisms. The sonication effluent was plated to trypticase soy agar to quantitate the adherent organisms. Adherence was significantly greater (p less than 0.01) to VKD compared with preclotted VKD and ACD at 2, 4, 8, and 24 hours. Four of the five study strains demonstrated significantly greater adherence to VKD than to either ACD or preclotted VKD. Adherence of S. epidermidis increased with exposure time. Albumin bonded to velour-knitted Dacron does not increase coagulase-negative staphylococcal adherence compared with the noncoated vascular prostheses. Binding albumin to vascular prostheses does not increase the risk of staphylococcal colonization.

A prospective study of the microflora of nonpuerperal breast abscess.

The majority of reports concerning nonpuerperal breast abscess (NPBA) identify aerobic and facultative bacterial isolates as the predominant flora in this disease. In the present study, fine-needle aspiration was performed in 29 women with NPBA; 12 (41%) of the patients had a history of chronic NPBA. The mean age of patients was 39.2 years. The aspirated material was cultured both anaerobically and aerobically. A total of 108 bacterial strains were recovered from 32 specimens; two specimens yielded no bacterial growth. A mean of 3.6 different bacteria were recovered from each culture-positive specimen. Anaerobic recovery outweighed aerobic-facultative recovery by a factor of 2:1. Significantly, 37 strains (five aerobes and 32 anaerobes) were harvested only from enriched broth subcultured for four to 14 days after initial culture processing. Coagulase-negative staphylococci (60% of total aerobes) and peptostreptococci (47% of total anaerobes) were the predominant bacterial isolates. These findings indicate that NPBA is due to a mixed flora with a major anaerobic component. Furthermore, the results suggest that routine cultures often overlook the involvement of anaerobes in these infections.

The efficacy of oral antimicrobials in reducing aerobic and anaerobic colonic mucosal flora.

We investigated the impact of intestinal antisepsis on the colonic mucosa-associated flora. Four groups of dogs were studied: group A received no bowel preparation, group B received a three-day clear-liquid diet, group C underwent mechanical cleansing of the bowel, and group D had mechanical cleansing followed by oral neomycin and erythromycin. Mucosal biopsy specimens were obtained for bacteriologic and scanning electron microscopic (SEM) studies. No significant difference in recovery of mucosal bacteria was observed between groups A and B. A significant decrease in recovery of aerobes was observed in group C, and a significant decrease in both aerobes and anaerobes was observed in group D compared with group A; Enterobacteriaceae and Bacteroides were either eliminated or greatly reduced. The SEM analysis of group D revealed a marked decrease in mucosa-associated microflora compared with groups B and C. Oral neomycin-erythromycin produced a significant quantitative reduction in the colonic mucosa-associated bacterial population, including the potentially pathogenic Escherichia coli and Bacteroides fragilis group isolates. These mucosa-associated bacteria are a likely source of contamination of the abdominal cavity and wound at the time of colon surgery.

Comparative in vitro beta-lactam activity against aerobic and anaerobic surgical isolates.

The comparative in vitro activity of cefoxitin, piperacillin, cefotetan, and ceftizoxime was compared against 843 surgical microbial isolates. All compounds exhibited excellent activity against the streptococcal isolates. Antimicrobial activity was poor for Staphylococcus aureus and S. epidermidis. Cefotetan activity against the Enterobacteriaceae was comparable to ceftizoxime (greater than 95% susceptible). Resistance rates of 0, 1, 5, and 2% were observed with cefoxitin, piperacillin, cefotetan, and ceftizoxime against the anaerobic cocci and anaerobic gram-positive non-spore-forming rods. Ninety-six and ninety-nine percent of the clostridial strains were susceptible to cefotetan and piperacillin, respectively. Piperacillin, cefotetan, and ceftizoxime exhibited similar activity against Bacteroides fragilis (resistance less than 10%). Cefotetan and cefoxitin exhibited poor activity against Bacteroides distasonis, B. ovatus, and B. thetaiotaomicron. Antimicrobial activities were comparable for the four drugs against other Bacteroides and Fusobacterium species. The results demonstrate that all four compounds exhibited broad antimicrobial activity against facultative and obligate anaerobic surgical isolates from intraabdominal and soft tissue infections.

Fibrous ball: a new manifestation of chronic defibrillator and pacemaker infection.

Two patients with unusual manifestation of long-term infection of implantable cardioverter defibrillator and pacemaker were examined. Complete explanation of the defibrillator and pacemaker was done in both patients. New devices were subsequently implanted.

Pharmacoeconomic analysis of ampicillin-sulbactam versus cefoxitin in the treatment of intraabdominal infections.

We conducted a retrospective pharmacoeconomic analysis of a prospective, multicenter, double-blind, randomized, controlled trial comparing the beta-lactamase inhibitor combination ampicillin-sulbactam (96 patients) and the cephalosporin cefoxitin (101) in the treatment of intraabdominal infections. An institutional perspective was adopted for the analysis. The primary outcomes of interest were cure and failure rates, development of new infection, and antibiotic-related adverse events. Epidemiologic data pertaining to outcomes was retrieved primarily from the trial, although results of other published studies were taken into consideration through extensive sensitivity analyses. Data pertaining to potential resource use and economic impact were retrieved mainly from the University Health Consortium and hospital-specific sources. When considering only costs associated with drug acquisition through cost-minimization analysis, a potential savings of $37.24/patient may be realized with ampicillin-sulbactam relative to cefoxitin based on an average 7-day regimen. Outcome data collected for the entire hospitalization during the trial revealed an approximately 9% greater frequency of failure with cefoxitin relative to ampicillin-sulbactam. When considering all outcomes of interest in the initial base-case analysis, a potential cost savings of approximately $890/patient may be realized with ampicillin-sulbactam relative to cefoxitin. In assessing the impact of the significant variability in probability and cost estimates, Monte Carlo analysis revealed a savings of $425/patient for ampicillin-sulbactam over cefoxitin (95% CI -$618 to $1516 [corrected]). Given the model assumptions, our analysis suggests a 78% certainty level that savings will be experienced when ampicillin-sulbactam is chosen over cefoxitin.

Pharmacodynamics of antimicrobial therapy in surgery.

INTRODUCTION: "Pharmacodynamics" refers to the relationship of drug concentrations in serum or tissues to effects on biologic systems. Concepts used to describe antimicrobial pharmacodynamics include the minimal inhibitory concentration (MIC), the minimal bactericidal concentration (MBC), and serum bactericidal titers (SBT), as well as post-antibiotic effect. METHODS: Pertinent published literature was identified through a MEDLINE search. RESULTS: Aminoglycosides have a concentration-dependent effect on bacteria killing and possess a relatively long postantibiotic effect. Given these characteristics, single-daily dosing, where the total daily dose with a traditional aminoglycoside regimen is given as one dose, may be more efficacious compared with more frequent dosing. For beta-lactam antimicrobials, bacterial killing is related to the duration of time that the free drug concentration exceeds the bacterial MIC. Beta-lactam antimicrobials have been shown to have no, or a short postantibiotic effect. Beta-lactam antimicrobials may be more effective when administered as continuous intravenous infusions. CONCLUSIONS: Pharmacodynamic variation may result from differences in drug sensitivity among individuals and the nature of the interaction between antimicrobials and microorganisms. Proper use of pharmacokinetic and pharmacodynamic principles can result in more effective and less toxic antimicrobial regimens.

Small bowel myoelectric activity in peritonitis.

Peritonitis is associated clinically with paralytic ileus, but the physiologic mechanisms of the effects of peritonitis on bowel myoelectric activity have not been explored. Bipolar electrodes were inserted into the rats, and myoelectric control recordings were obtained for 4 h/d for 5 consecutive days. Peritonitis was then induced, and myoelectric recordings were again obtained. Each animal served as its own control. Prior to induction of peritonitis (control), phase I, II, and III myoelectric activity was present in all recordings. The cycle duration of the migrating myoelectric complex was 17.17 +/- 0.39 minutes, and the migration velocity of phase III was 0.61 +/- 0.02 cm/min. The most striking feature during peritonitis was the complete inhibition of phase II activity. Phase III activity, however, was present with a cycle duration of 16.69 +/- 0.42 minutes. This study shows that some features of intestinal myoelectric activity (phase III) are preserved during episodes of peritonitis, and others are changed (phase I) or lost (phase II). Disappearance of phase II activity in this type of ileus emphasizes its importance in normal small bowel motility.

Untreated diabetes mellitus promotes intestinal microbial overgrowth.

Gastrointestinal dysfunction is a common secondary complication of insulin-dependent diabetes mellitus, yet its etiology is unclear. Enteric microbial overgrowth may play a role. To quantitate the changes in mucosal-adherent enteric microbial populations in untreated diabetes mellitus and to assess the impact of two forms of insulin replacement therapy upon enteric microbial populations, age-matched male Lewis rats were rendered diabetic by the administration of intravenous streptozotocin (55 mg/kg). After diabetes was confirmed (blood glucose level greater than 250 mg/dL), rats were divided into three groups: no treatment (no insulin), treatment with daily insulin to maintain normoglycemia (3 to 7 units of protamine zinc insulin subcutaneously), or transplantation with a vascularized heterotopic duct-ligated pancreatic isograft. After 1 month, rats were killed, and segments of the proximal, middle, and distal small bowel were obtained. Mucosal samples were rinsed in phosphate-buffered saline to remove nonadherent bacteria prior to aerobic and anaerobic culturing. Microbial recovery was expressed as the log10 colony-forming unit/mg tissue wet weight. Untreated diabetes resulted in an overgrowth of mucosal-associated small bowel aerobic and anaerobic microbial populations compared with populations in normal nondiabetic age-matched control rats. Insulin treatment and pancreatic transplantation prevented microbial overgrowth in the diabetic small intestine. Pancreatic transplantation resulted in strict normoglycemia equivalent to that in nondiabetic control rats, whereas insulin treatment resulted in slightly higher blood glucose levels at sacrifice and wide fluctuations in blood glucose levels compared with nondiabetic control rats. These data suggest that sustained normalization of glucose levels is not required to prevent microbial overgrowth in diabetic rats.