Rabih O. Darouiche

Chlorhexidine–Alcohol versus Povidone–Iodine for Surgical-Site Antisepsis

BACKGROUND Since the patients skin is a major source of pathogens that cause surgical-site infection, optimization of preoperative skin antisepsis may decrease postoperative infections. We hypothesized that preoperative skin cleansing with chlorhexidine-alcohol is more protective against infection than is povidone-iodine. METHODS We randomly assigned adults undergoing clean-contaminated surgery in six hospitals to preoperative skin preparation with either chlorhexidine-alcohol scrub or povidone-iodine scrub and paint. The primary outcome was any surgical-site infection within 30 days after surgery. Secondary outcomes included individual types of surgical-site infections. RESULTS A total of 849 subjects (409 in the chlorhexidine-alcohol group and 440 in the povidone-iodine group) qualified for the intention-to-treat analysis. The overall rate of surgical-site infection was significantly lower in the chlorhexidine-alcohol group than in the povidone-iodine group (9.5% vs. 16.1%; P=0.004; relative risk, 0.59; 95% confidence interval, 0.41 to 0.85). Chlorhexidine-alcohol was significantly more protective than povidone-iodine against both superficial incisional infections (4.2% vs. 8.6%, P=0.008) and deep incisional infections (1% vs. 3%, P=0.05) but not against organ-space infections (4.4% vs. 4.5%). Similar results were observed in the per-protocol analysis of the 813 patients who remained in the study during the 30-day follow-up period. Adverse events were similar in the two study groups. CONCLUSIONS Preoperative cleansing of the patients skin with chlorhexidine-alcohol is superior to cleansing with povidone-iodine for preventing surgical-site infection after clean-contaminated surgery. (ClinicalTrials.gov number, NCT00290290.)

A Comparison of Two Antimicrobial-Impregnated Central Venous Catheters

BACKGROUND The use of central venous catheters impregnated with either minocycline and rifampin or chlorhexidine and silver sulfadiazine reduces the rates of catheter colonization and catheter-related bloodstream infection as compared with the use of unimpregnated catheters. We compared the rates of catheter colonization and catheter-related bloodstream infection associated with these two kinds of antiinfective catheters. METHODS We conducted a prospective, randomized clinical trial in 12 university-affiliated hospitals. High-risk adult patients in whom central venous catheters were expected to remain in place for three or more days were randomly assigned to undergo insertion of polyurethane, triple-lumen catheters impregnated with either minocycline and rifampin (on both the luminal and external surfaces) or chlorhexidine and silver sulfadiazine (on only the external surface). After their removal, the tips and subcutaneous segments of the catheters were cultured by both the roll-plate and the sonication methods. Peripheral-blood cultures were obtained if clinically indicated. RESULTS Of 865 catheters inserted, 738 (85 percent) produced culture results that could be evaluated. The clinical characteristics of the patients and the risk factors for infection were similar in the two groups. Catheters impregnated with minocycline and rifampin were 1/3 as likely to be colonized as catheters impregnated with chlorhexidine and silver sulfadiazine (28 of 356 catheters [7.9 percent] vs. 87 of 382 [22.8 percent], P<0.001), and catheter-related bloodstream infection was 1/12 as likely in catheters impregnated with minocycline and rifampin (1 of 356 [0.3 percent], vs. 13 of 382 [3.4 percent] for those impregnated with chlorhexidine and silver sulfadiazine; P<0.002). CONCLUSIONS The use of central venous catheters impregnated with minocycline and rifampin is associated with a lower rate of infection than the use of catheters impregnated with chlorhexidine and silver sulfadiazine.

Candida Infections of Medical Devices

SUMMARY The number of indwelling medical devices is escalating, and an increasing proportion of device-related infections are being caused by Candida spp. Candida spp. produce biofilms on synthetic materials, which facilitates adhesion of the organisms to devices and renders them relatively refractory to medical therapy. Management of device-related Candida infections can be challenging. Removal of the infected device is generally needed to establish cure of Candida infections of medical devices. However, since the pathogenesis of Candida bloodstream infection is complicated, more studies are necessary to determine the role of catheter exchange in patients with both gastrointestinal tract mucositis and indwelling catheters. The medical and economic impact of these infections is enormous.

Central Venous Catheters Coated with Minocycline and Rifampin for the Prevention of Catheter-Related Colonization and Bloodstream Infections: A Randomized, Double-Blind Trial

See related articles on pp 257-266 and 275-280 and editorial comment on pp 304-306. Central venous catheters are indispensable in the treatment of critically and chronically ill patients, but they are the leading cause of primary nosocomial bloodstream infection [1, 2]. A study of hospitals in the National Nosocomial Infection Surveillance System, conducted between 1986 and 1990, showed that rates of bloodstream infection were substantially higher in patients who were in intensive care units and had intravascular devices than in those who did not have such devices [3]. To decrease the risk for catheter colonization and infection, antiseptic and antibiotic agents have been applied topically at the insertion site [4-6]. More recently, the use of antimicrobial flush solutions has been proposed [7]. However, coating venous catheters with antiseptic or antimicrobial agents may have an even more pronounced protective effect against colonization and infection, particularly if both the external and internal surfaces of the device are coated. Since 1990, several types of antiseptic or antimicrobial vascular catheter coatings have been developed and studied [8, 9]. Maki and colleagues [9] investigated central venous catheters coated with chlorhexidine-silver sulfadiazine; the coated catheters seemed less likely than the uncoated catheters to be associated with bloodstream infections. We recently coated vascular catheters with a combination of minocycline and rifampin after treatment with the tridodecylmethyl-ammonium chloride surfactant. In vitro, these catheters were shown to have broad-spectrum antimicrobial inhibitory activity that was significantly superior to the activity of catheters coated with chlorhexidine-silver sulfadiazine [10, 11]. The catheters coated with minocycline and rifampin were also found to be highly efficacious in preventing catheter colonization and subcutaneous infection in a rabbit model [11]. In a double-blind, randomized clinical trial, we studied the efficacy of catheters that were treated with tridodecylmethyl-ammonium chloride and coated with minocycline and rifampin in preventing catheter colonization and bloodstream infection in hospitalized patients. Methods Study Sample Our study was conducted simultaneously at five university-based hospitals in the Texas Medical Center in Houston: The University of Texas M.D. Anderson Cancer Center (518 beds), Veterans Administration Medical Center (1050 beds), Hermann Hospital (600 beds), Ben Taub General Hospital (580 beds), and The Methodist Hospital (904 beds). The study began on 1 September 1994 and ended on 27 March 1995. Hospitalized patients 18 years of age or older who required a triple-lumen polyurethane central venous catheter at a new insertion site were asked to participate. We excluded pregnant women, patients who were allergic to rifampin or tetracycline, patients with dermatitis or a burn over the insertion site, and patients for whom the anticipated duration of catheterization was less than 3 days. All patients gave informed consent. Randomization All catheters were triple-lumen, polyurethane, 7 French, and 20 cm long (Cook Critical Care, Bloomington, Indiana). The coated catheters were pretreated with tridodecylmethyl-ammonium chloride and then coated, 18 hours later, with minocycline and rifampin. The levels of minocycline and rifampin on the external and internal surfaces of coated catheters before insertion, as determined by high-performance liquid chromatography, were 139.3 g/cm and 13.9 g/cm, respectively. Control catheters were untreated and uncoated. All catheters were gas sterilized and placed in identical trays, and each tray was assigned an identification number. The trays were then randomly assigned into blocks of six: three with coated catheters and three with control catheters. Each block of trays was placed in boxes by Cook Critical Care, and the boxes were shipped to the five hospitals. When a patient was determined to be eligible, a tray was removed from the box (trays were removed one at a time, in sequential order from top to bottom), and that catheter was used for the patient. The catheter identification number was recorded on a data entry form and on the patients medical chart; neither the patient nor the clinician who inserted the device knew which catheter (coated or uncoated) had been used. Catheter Insertion and Care Study catheters were inserted into the subclavian vein, internal jugular vein, or femoral vein of patients who had no other indwelling catheter. Study catheters were not exchanged over guidewires. Maximal sterile barrier precautions were taken, including use of a sterile gown, sterile gloves, full sterile drapes, a mask, and a cap. At the time of catheter insertion and at each dressing change, the insertion site was cleaned with chlorhexidine gluconate (at The Methodist Hospital) or 10% povidone-iodine scrub (at all other hospitals). In each case, the preparation was applied to the skin for 2 minutes before catheter insertion. The insertion site was then covered with sterile gauze and taped securely. The insertion site was inspected every 72 hours (during a dressing change) for evidence of infection, such as erythema, purulence, swelling, or tenderness over the catheter. During follow-up, the following information was obtained for all patients: site of catheter insertion; dates of catheter placement and removal; occurrence of difficulties and violations of aseptic technique during insertion or removal, if any; reason for using the catheter (chemotherapy, total parenteral nutrition, administration of blood products, or a combination of these reasons); type of dressing; and reason for catheter removal. In addition, clinical data were obtained on underlying disease, neutrophil and platelet counts, antibiotic therapy administration, other therapeutic interventions administered during the period of catheterization, and the presence or absence of fever and infection during catheterization. The catheter remained in place until it was no longer needed; until a specific event, such as catheter-related infection, necessitated its removal; or for 28 days, whichever occurred first. Microbiological Methods Quantitative Cultures of Central Venous Catheters The entire catheter was removed aseptically, and 4-cm segments were cut from the catheter tip and the subcutaneous section. These segments were semiquantitatively cultured by using the roll-plate method; the same segment was then quantitatively cultured by using the sonication method [12-14]. Organisms recovered by either method were fully identified according to standard microbiological methods. Coagulase-negative staphylococci were classified as gram-positive cocci in clusters that produced catalase but not coagulase and were categorized according to species by using the Staph-Ident System (Analytab Products, Plainview, New Jersey). All hospitals used the same methods for culture. Skin Cultures To determine whether bacteria became resistant to the antibiotics that coated the study catheters, skin samples obtained from the insertion site were cultured at the time of insertion and within 24 hours after catheter removal, as described elsewhere [15]. Organisms recovered from the insertion site were fully identified by using standard microbiological methods. Antimicrobial Resistance We used the modified Kirby-Bauer technique to test the antimicrobial activity of the catheters coated with minocycline and rifampin against all organisms isolated from indwelling coated catheters at the time of catheter removal [16]. The zones of inhibition against staphylococci cultured from coated catheters were compared with those of uncoated catheters. The minimal inhibitory concentration (MIC) of minocycline hydrochloride (Lederle Laboratories, Pearl River, New York) and rifampin (Ciba-Geigy Corp., Summit, New Jersey) against staphylococcal organisms that colonized the catheter tip, subcutaneous segments, and adjacent skin insertion sites of the coated catheters was determined. A microbroth dilution method was used to determine the MIC in accordance with guidelines established by the National Committee for Clinical Laboratory Standards [17]. Definitions The definitions adopted for our study were proposed by the Centers for Disease Control and Prevention [18]. Colonization of a central venous catheter was defined as 1) the isolation from either the tip or the subcutaneous segment of 15 or more colony-forming units of any organism by the rollplate technique or 2) isolation of more than 1000 colony-forming units of any organism by the sonication technique. Catheter-related bloodstream infection was defined as the isolation of microorganisms from the bloodstream (blood was obtained through venipuncture, not through the catheter) of a patient who had concurrent clinical manifestations of sepsis and no source for the bloodstream infection other than the vascular catheter. In addition, the catheter had to be colonized with the same organism (same species and same antibiogram). To confirm the diagnosis of catheter-related bloodstream infection, DNA molecular typing done using pulse-field gel electrophoresis was performed on organisms that were of the same species, had the same antibiogram, and were isolated from the catheter and blood during the period of catheterization. Patients were considered to have fever if the oral body temperature was greater than 38 C. Neutropenia was defined as a polymorphonuclear count of fewer than 1000 cells/mm3. Thrombocytopenia was defined as a platelet count of fewer than 100 000 cells/mm3. Molecular Typing Molecular typing was performed by using pulse-field gel electrophoresis. Identical organisms with similar DNA profiles that were isolated from a segment of the colonized catheter and from the bloodstream confirmed the diagnosis of catheter-related bloodstream infection. However, a mismatch did not rule out such a diagnosis because catheter coloniza

Bacterial spinal epidural abscess. Review of 43 cases and literature survey.

We have reviewed our experience with 43 cases of bacterial spinal epidural abscess, as well as previously reported series of cases. We found a striking male predominance of the disease, accounting for 86% of cases. Most patients had some underlying conditions that predisposed to infection, a prior infection at a distant site, or an abnormality or trauma to the spine. Presenting symptoms included backache (72%), radicular pain (47%), weakness of an extremity (35%), sensory deficit (23%), bladder or bowel dysfunction (30%), and frank paralysis (21%). Patients cared for in public hospitals tended to seek medical attention in later stages of the disease than patients admitted to private hospitals. Spinal epidural abscess was the suspected diagnosis in only 40% of the cases; the remainder of the time various other infections, tumors, neurologic diseases, or degenerative conditions were considered. Patients in whom the diagnosis of spinal epidural abscess was not initially entertained on admission suffered delays in diagnosis and experienced neurologic deterioration. Staphylococcus aureus was the predominant pathogen (65%) and was associated with positive blood cultures in nearly every case; aerobic or facultative gram-negative bacilli were next most common. Coagulase-negative staphylococci caused infection only in patients who had previous spinal instrumentation. Although analysis of CSF was abnormal in the majority of cases, abnormalities were nonspecific, Gram stain was always negative and culture was rarely diagnostic. Abscesses extended over an average of 4 vertebrae, and the majority were located in the lumbar region followed by thoracic and cervical regions. Unlike previous series, we noted an equal frequency of anterior and posterior epidural abscesses; although differences were not statistically significant, posterior abscesses tended to be more extensive but less commonly associated with radiographic abnormalities of osteomyelitis. Myelography revealed an abnormality in every case in which it was done. Computerized tomographic scanning after intrathecal injection of contrast material always provided additional useful information. Even though magnetic resonance imaging was diagnostic in only 4 of 5 cases (80%) in our series, this test is noninvasive and clearly delineates the location and nature of spinal lesion. It should, therefore, probably replace myelography as an initial definitive study in patients suspected of having spinal infection. Plain roentgenograms and nuclear scans contributed little useful information that was not already available from other radiographic procedures. Surgical drainage together with antibiotics was the treatment of choice; 35 of our 43 patients underwent operative intervention. The preoperative status clearly predicted the final neurologic outcome.(ABSTRACT TRUNCATED AT 400 WORDS)

Antibiotics and prevention of microbial colonization of catheters

Slime-producing staphylococci frequently colonize catheters, and when they are embedded in biofilm, they become resistant to various antibiotics. In the study that is described, the comparative efficacies of vancomycin, clindamycin, novobiocin, and minocycline, alone or in combination with rifampin, were tested in an in vitro model of colonization. The model consisted of the modified Robbins device with antibiotic-impregnated cement filling the lumen of catheter segments. The synergistic combination of minocycline and rifampin was the most efficacious in preventing bacterial colonization of slime-producing strains of Staphylococcus epidermidis and Staphylococcus aureus to catheter surfaces. A similar trend was observed when the inhibitory activities of polyurethane catheters coated with minocycline and rifampin were compared with the inhibitory activities of catheters coated with other antimicrobial agents. The inhibitory activities of catheters coated with minocycline and rifampin against S. epidermidis, S. aureus, and Enterococcus faecalis strains, for example, were significantly better than those of catheters coated with vancomycin (P < 0.05). The inhibitory activities of catheters coated with minocycline and rifampin against gram-negative bacilli and Candida albicans were comparable to those of catheters coated with ceftazidime and amphotericin B, respectively. We found that the combination of minocycline and rifampin is unique and highly effective in preventing the colonization of catheters with slime-producing staphylococci and that it also displays a broad-spectrum inhibitory activity against gram-negative bacteria and yeast cells.

Efficacy and Safety of Weekly Dalbavancin Therapy for Catheter-Related Bloodstream Infection Caused by Gram-Positive Pathogens

BACKGROUND Catheter-related bloodstream infections (CR-BSIs) are associated with substantial mortality, prolongation of hospital stay, and increased cost of care. Dalbavancin, a new glycopeptide antibiotic with unique pharmacokinetic properties that have allowed clinical development of a weekly dosing regimen, possesses excellent activity against clinically important gram-positive bacteria, suggesting utility in the treatment of patients with CR-BSIs. METHODS A phase 2, open-label, randomized, controlled, multicenter study of 75 adult patients with CR-BSIs compared treatment with intravenous dalbavancin, administered as a single 1000-mg dose followed by a 500-mg dose 1 week later, with intravenous vancomycin, administered twice daily for 14 days. Gram-positive bacteria isolated in this study included coagulase-negative staphylococci (CoNS) and Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA). RESULTS Infected patients who received weekly dalbavancin (n=33) had an overall success rate (87.0%; 95% confidence interval [CI], 73.2%-100.0%) that was significantly higher than that of those who received vancomycin (n=34) (50.0%; 95% CI, 31.5%-68.5%). Adverse events and laboratory abnormalities were generally mild and were comparable for the 2 drugs. CONCLUSIONS Dalbavancin thus appears to be an effective and well-tolerated treatment option for adult patients with CR-BSIs caused by CoNS and S. aureus, including MRSA.

Anti-Infective Efficacy of Silver-Coated Medical Prostheses

Medical prostheses constitute an indispensable component of modern health care. Like other approaches of medical intervention, the insertion of medical prostheses can be associated with serious complications. The ongoing advances in the mechanical properties of medical prostheses have not necessarily resulted in lower rates of prosthesis-related infection. Infection remains the most common serious complication of medical prostheses. For instance, vascular catheters account for most cases of nosocomial bloodstream infection [1], and catheterrelated urinary tract infection is the most frequent nosocomial infection [2]. Two decades ago, infections associated with medical prostheses accounted for about half of all nosocomial infections [2]. Today, with their increasing use, medical prostheses are expected to cause a larger portion of cases of nosocomial infections, particularly in the subpopulations of immunocompromised, chronically ill, and elderly subjects. Infections associated with medical prostheses result in major morbidity and can be life-threatening. For instance, the mortality associated with prosthetic valve endocarditis ranges from 30% to 80% in patients with early-onset infection and from 20% to 40% in patients with late-onset endocarditis [3]. Often, infections associated with medical prostheses are very expensive to manage, and their cure requires removal of the infected prosthesis. For example, findings from the Dutch Trauma Trial indicated a mean cost of

Efficacy of antimicrobial-impregnated bladder catheters in reducing catheter-associated bacteriuria: a prospective, randomized, multicenter clinical trial

22,000 (in 1991 dollars) to treat a patient who developed a deep wound infection after internal fixation of a closed fracture [4].

Management of Central Venous Catheters in Patients with Cancer and Candidemia

OBJECTIVES To examine the efficacy of bladder catheters impregnated with minocycline and rifampin in reducing catheter-associated bacteriuria. METHODS A prospective, randomized clinical trial was conducted at five academic medical centers. Patients undergoing radical prostatectomy were randomized to receive intraoperatively either regular silicone bladder catheters (control catheters) or silicone bladder catheters impregnated with minocycline and rifampin (antimicrobial-impregnated catheters). Catheters remained in place for a mean of 2 weeks. Urine cultures were obtained at about 3, 7, and 14 days after catheter insertion. Bacteriuria was defined as the growth of organism(s) in urine at a concentration of 10(4) colony-forming units per milliliter or greater. RESULTS Kaplan-Meier analysis demonstrated that it took significantly longer for patients (n = 56) who received the antimicrobial-impregnated catheters to develop bacteriuria than those (n = 68) who received the control catheters (P = 0.006 by the log-rank test). Patients who received the antimicrobial-impregnated catheters had significantly lower rates of bacteriuria than those in the control group both at day 7 (15.2% versus 39.7%) and at day 14 (58.5% versus 83.5%) after catheter insertion. Patients who received the antimicrobial-impregnated catheters had significantly lower rates of gram-positive bacteriuria than the control group (7.1% versus 38.2%; P <0.001) but similar rates of gram-negative bacteriuria (46.4% versus 47.1%) and candiduria (3.6% versus 2.9%). The antimicrobial-impregnated catheters provided zones of inhibition against Enterococcus faecalis and Escherichia coli, both at baseline and on removal. CONCLUSIONS Bladder catheters impregnated with minocycline and rifampin significantly reduced the rate of gram-positive catheter-associated bacteriuria up to 2 weeks after catheter insertion.