Mechanism of salicylate-mediated inhibition of biofilm in Staphylococcus epidermidis.

The inclusion of 5 mM salicylic acid (SAL) in medium inhibited both growth and biofilm production by Staphylococcus epidermidis by up to 55%. The inhibition was not due primarily to chelation of cations. Excess divalent cations restored growth and biofilm production in chelated medium and in medium containing EDTA but not in medium containing SAL. ELISA analyses demonstrated that SAL inhibited production of teichoic acid, slime-associated proteins, and type 1 antigen by as much as 95%. However, it inhibited polysaccharide/adhesin production by only 50%--a figure paralleling the reduction in growth. The equivalent inhibitory effects of SAL on a pair of isogenic strains, one of which was a polysaccharide/adhesin-deficient mutant, confirmed that the primary effect of SAL was a reduction in the production of biofilm components rather than a reduction in the retention of these components in the slime layer prior to assembly into a biofilm.

Skin and mucous membrane contacts with blood during surgical procedures: risk and prevention.

OBJECTIVE: To study the epidemiology and preventability of blood contact with skin and mucous membranes during surgical procedures. DESIGN: Observers present at 1,382 surgical procedures recorded information about the procedure, the personnel present, and the contacts that occurred. SETTING: Four US teaching hospitals during 1990. PARTICIPANTS: Operating room personnel in five surgical specialties. MAIN OUTCOME MEASURES: Numbers and circumstances of contact between the patient's blood (or other infective fluids) and surgical personnel's mucous membranes (mucous membrane contacts) or skin (skin contacts, excluding percutaneous injuries). RESULTS: A total of 1,069 skin (including 620 hand, 258 body, and 172 face) and 32 mucous membrane (all affecting eyes) contacts were observed. Surgeons sustained most contacts (19% had > or = 1 skin contact and 0.5% had > or = 1 mucous membrane-eye contact). Hand contacts were 72% lower among surgeons who double gloved, and face contacts were prevented reliably by face shields. Mucous membrane-eye contacts were significantly less frequent in surgeons wearing eyeglasses and were absent in surgeons wearing goggles or face shields. Among surgeons, risk factors for skin contact depended on the area of contact: hand contacts were associated most closely with procedure duration (adjusted odds ratio [OR], 9.4; > or = 4 versus < 1 hour); body contacts (arms, legs, and torso) with estimated blood losses (adjusted OR, 8.4; > or = 1,000 versus < 100 mL); and face contacts, with orthopedic service (adjusted OR, 7.5 compared with general surgery). CONCLUSION: Skin and mucous membrane contacts are preventable by appropriate barrier precautions, yet occur commonly during surgery. Surgeons who perform procedures similar to those included in this study should strongly consider double gloving, changing gloves routinely during surgery, or both.

A novel antibiofilm technology for contact lens solutions.

PURPOSE: Nonsteroidal anti-inflammatory drugs, including sodium salicylate, inhibit extracellular bacterial biofilm production. The authors studied the effect of the addition of sodium salicylate on bacterial adherence and biofilm formation on contact lenses and cases and commonly used medical polymers. METHODS: The study was done in vitro with bacterial adherence and biofilm measured on lenses and cases that were exposed to saline contaminated with Staphylococcus epidermidis and Pseudomonas aeruginosa with and without 1 and 3 mm sodium salicylate. Bacterial adherence to contact lenses was quantitated by a vortex assay and by scanning electron microscopy. Biofilm formation on contact lens cases and other polymers was measured by an optical density assay and a radiolabeling assay. RESULTS: Inhibition of biofilm formation was demonstrated on plastic contact lens cases in a dose-related manner with 1 and 3 mm sodium salicylate. A dose-related decrease in bacterial adherence also was noted. Assays with contact lenses also demonstrated less adherence in the presence of sodium salicylate. Electron micrographs of the contact lens showed less biofilm, most noticeable with 3 mm salicylate. Other studies demonstrated decreased adherence of S. epidermidis to polyethylene and polystyrene. Sodium salicylate also decreased biofilm on plastic tissue culture wells, but sorbic acid paradoxically increased deposition. CONCLUSION: The authors found that the addition of low-dose sodium salicylate to saline decreased the adherence of S. epidermidis and P. aeruginosa to contact lenses and lens cases. Biofilm production also was decreased on the lens cases and on medical polymers used to make plastic cases. These studies suggest that sodium salicylate deserves additional study to determine its use in contact lens solutions.

Multidrug-resistant Enterococcus faecium. An untreatable nosocomial pathogen.

The prevalence of enterococci and nosocomial pathogens has increased over the past 15 years. They have become increasingly resistant to agents traditionally useful in the treatment of invasive diseases due to enterococci. Vancomycin resistance, first described in clinical isolates in 1988, has disseminated worldwide. It is usually associated with high-level resistance to penicillins and aminoglycosides rendering the treatment of patients with vancomycin-resistant enterococci very difficult. Several investigators have reported mortality rates greater than 50% for vancomycin-resistant enterococcal bacteraemia. Risk factors associated with vancomycin-resistant enterococcal bacteraemia include prolonged hospital stay, neutropenia, prior oral or parenteral vancomycin use, and broad spectrum antibiotics. Since there is no uniformly effective antimicrobial therapy for patients infected with vancomycin-resistant enterococci, preventing of the spread of infection with the rigorous application of barrier precautions and other infectious control techniques is of paramount importance.

Salicylic acid prevents the adherence of bacteria and yeast to silastic catheters.

During the pathogenesis of catheter-related urinary tract infection, bacteria attach to the catheter and migrate along a biofilm into the bladder. We studied the effect of coating silastic catheters with salicylic acid on bacterial and yeast adherence. An agar roll technique, bioluminescent assay, and radiolabeling study all produced consistent results. There was a dose related inhibition of adherence with Pseudomonas aeruginosa, Enterobacter aerogenes, Klebsiella pneumoniae, Candida albicans, and Enterococcus faecalis. Inhibition of over 90% was noted with Enterobacter and Pseudomonas. Similar results were obtained in broth and synthetic urine. A dose related reduction in adherence was seen with all gram-negative rods and yeast as measured by a radiolabeling assay. TDMAC was used to bind the salicylic acid to the catheters with > 95% inhibition of the gram-negative rods. These studies suggest the potential role of coating catheters with salicylic acid to reduce bacterial adherence and urinary tract infection.

The use of salicylic acid to prevent the adherence of Escherichia coli to silastic catheters.

We studied the effect of salicylic acid on the attachment of Escherichia coli to silastic catheters. Silastic catheters were exposed to organisms grown in the presence of subinhibitory concentrations (1 and 5 mM.) of salicylic acid. An agar rolling technique demonstrated 59% and 79% inhibition of adherence with the 2 concentrations, respectively. Silastic catheters were also pretreated by heating and then incubating in 200 mM. and 600 mM. salicylic acid in 95% ethanol at -20C. After incubation in 10(4) CFU/ml. E. coli for 5 hours at 37C, 62% and 93% inhibition of adherence was observed. Acetylsalicylic acid and ibuprofen did not demonstrate similar results. Similar inhibition (82% and 95%) was observed despite preincubation of the treated catheters in sterile urine for 4 days. A bioluminescent assay of bacterial adherence also revealed inhibition only with salicylic acid. Studies using 3H-leucine demonstrated a decrease in adherence with higher concentrations of salicylic acid. Finally, tridodecylmethylammonium was used to bind salicylic acid to silastic catheters. After a 5-hour incubation in 10(4) CFU/ml. at 37C, 94% and 99% inhibition were observed with 200 and 600 mM. salicylic acid. Salicylic acid decreases adherence of E. coli to silastic catheters. This observation may be of value in designing catheters less likely to cause urinary tract infection.

The use of nonsteroidal antiinflammatory drugs to prevent adherence of Staphylococcus epidermidis to medical polymers.

The effect of salicylates and other nonsteroidal antiinflammatory drugs on the production of Staphylococcus epidermidis extracellular slime was studied. A dose-related decrease in slime production was observed with increasing concentrations of salicylic acid. S. epidermidis grown in 5 mM salicylic acid were less likely to adhere to Silastic, polyvinyl chloride, polyurethane, and Teflon catheters (P less than .006); strains grown in 2 mM salicylic acid, ibuprofen, indomethacin, or phenylbutazone were less adherent to Silastic catheters (P less than .001). Similar results were obtained with polyurethane catheters. S. epidermidis strains were less likely to adhere (43%-82% inhibition) to polyurethane catheters treated with 500 mM salicylic acid diluted in ethanol (P less than .0001). Similar differences were not observed with acetaminophen, ibuprofen, or acetylsalicylic acid. Adherence of radiolabeled S. epidermidis to salicylic acid-treated Silastic catheters demonstrated a dose-related reduction. The use of salicylic acid to coat medical devices may decrease the incidence of device-related infection.

Percutaneous injuries during surgical procedures.

OBJECTIVE: To study the numbers and circumstances of percutaneous injuries (eg, needle sticks, cuts) that occur during surgical procedures. Surgical personnel risk infection with blood-borne pathogens from percutaneous injuries; some injuries might also place patients at risk by exposing them to a health care worker's blood. DESIGN: Observers present at 1382 surgical procedures recorded information about the procedure, the personnel present, and percutaneous injuries that occurred. SETTING: Four US teaching hospitals during 1990. PARTICIPANTS: Operating room personnel in five surgical specialties. MAIN OUTCOME MEASURES: Numbers and circumstances of percutaneous injuries among surgical personnel and instances in which surgical instruments that had injured a worker recontacted the patient's surgical wound. RESULTS: Ninety-nine injuries occurred during 95 (6.9%) of the 1382 procedures. Seventy-six injuries (77%) were caused by suture needles and affected the nondominant hand (62 injuries [63%]), especially the distal forefinger. The risk of injury adjusted for confounding variables by logistic regression was higher during vaginal hysterectomy (odds ratio [OR], 3.5; 95% confidence interval [CI], 1.6 to 7.5) and lower during certain orthopedic procedures (OR, 0.2; CI, 0.1 to 0.7) than during 11 other types of procedures (reference group; OR, 1.0). Use of fingers rather than an instrument to hold the tissue being sutured was associated with 35 injuries (35%). Eighty-eight injuries (89%) were sustained by resident or attending surgeons; in 28 (32%) of the 88 injuries in surgeons, the sharp object that caused the injury recontacted the patient. CONCLUSION: Percutaneous injuries occur regularly during surgery, placing surgical personnel and, to a lesser extent, patients at risk for infection with blood-borne pathogens. Many such injuries may be preventable with changes in devices, techniques, or protective equipment; all such measures require careful evaluation to determine their efficacy in reducing injury and their effect on patient care.

Syndrome of severe skin disease, eosinophilia, and dermatopathic lymphadenopathy in patients with HTLV-II complicating human immunodeficiency virus infection.

Two intravenous drug users dually infected with human immunodeficiency virus type 1 (HIV-1) and human T-cell leukemia virus type II (HTLV-II) developed an unusual severe dermatitis characterized by progressive brawny induration, fissuring, and ulceration of the skin, with an associated CD8 cell infiltration in one patient. Both patients had persistent eosinophilia. Lymph node biopsy revealed dermatopathic lymphadenopathy, an unusual pathologic finding in HIV-1 infection but one seen in association with mycosis fungoides and other skin disorders. Two new isolates of HTLV-II virus were established from these patients and were identified as HTLV-II by Southern blotting. This type of skin disease and lymph node pathology has not been found in other intravenous drug users who have been infected with HIV-1 alone or in patients in other risk groups for HIV-1 infection. HTLV-II may play a role in this unique new disease pattern in patients infected with HIV-1.

Clinical significance of neutropenia in patients with human immunodeficiency virus infection.

OBJECTIVE: To determine the incidence of infection in human immunodeficiency virus (HIV)-infected patients during periods of neutropenia and non-neutropenia. To compare the infection rates in patients with HIV disease to those in a group hospitalized with neutropenia and hematologic malignancy. DESIGN: Prospective observational study conducted between December 1985 and December 1987 at a university teaching hospital. Thirty patients with documented acquired immunodeficiency syndrome (AIDS) and absolute T-helper cells less than 200 mm/mm3. All patients had a period of non-neutropenia following a neutropenic period (neutrophils less than 1000 cells/mm3). RESULTS: The rate of first infection during neutropenic and non-neutropenic periods for opportunistic infection and nonopportunistic infections were compared. There were no differences between infection rates for the two time periods for both types of infections. A subgroup of patient care days in which non-neutropenic days followed neutropenic days also was studied to eliminate selection bias. In this group, a comparison of infection rates also revealed no difference between neutropenic and non-neutropenic periods. An alternate analysis of the time until first infection during periods of neutropenia or non-neutropenia was done using the Kaplan-Meier product limit method. There was a longer infection-free period for the neutropenic group for opportunistic infections, but it was not statistically significant (p less than .1). In addition, we compared HIV-infected patients with a group of 37 patients with neutropenia from hematologic malignancy. There was a significantly higher rate of all infections, particularly bacteremias (p less than .001), in the group of patients with hematologic malignancies when compared with all subsets of patients with HIV disease. CONCLUSION: We conclude that patients with HIV disease and modest neutropenia do not have an increased risk of bacterial infection. The incidence of all infections is significantly greater in patients with neutropenia secondary to hematologic malignancy.

Enterococcal endocarditis: a comparison of prosthetic and native valve disease.

Between 1973 and 1987, 36 patients with 41 episodes of enterococcal endocarditis were seen at our institution. There were 22 episodes of native valve endocarditis (NVE) and 19 episodes of prosthetic valve endocarditis (PVE). The overall mortality before completion of therapy was 15% (18% due to NVE and 11% due to PVE). Among patients with NVE, involvement of the aortic valve was significantly associated with death or complicated illness (defined as the need for valve replacement before completion of antibiotic therapy or relapse of endocarditis after completion of therapy). Among patients who survived episodes of PVE, 69% were cured without surgical intervention. Gentamicin was administered in combination with a penicillin or vancomycin in the majority of episodes (mean duration of therapy with aminoglycosides: 5 weeks). Renal dysfunction occurred in 44% of patients who received gentamicin and occurred more frequently in patients with elevated serum creatinine levels before treatment. Our results suggest that enterococcal PVE can often be successfully treated with antibiotics alone, and they confirm the efficacy of gentamicin when it is administered in combination with cell wall-active agents for the treatment of endocarditis due to enterococci that lack high-level resistance to this agent.

Steroids for Pneumocystis carinii pneumonia and respiratory failure in the acquired immunodeficiency syndrome. A reassessment.

Patients with acquired immunodeficiency syndrome who have Pneumocystis carinii pneumonia (PCP) and respiratory failure have a high mortality. Previous reports have suggested that corticosteroids administered in conjunction with antibiotics improve the outcome in these patients. We reviewed our experience with adjunctive corticosteroids in 20 patients with acquired immunodeficiency syndrome and respiratory failure due to PCP to determine if this was the case. Fourteen patients responded to therapy with initial reversal of their respiratory failure. However, nine of these relapsed with recurrence of respiratory failure after steroid therapy was withdrawn. Eight (40%) of the patients remained alive and well 3 months or more following treatment. When the analysis was restricted to patients requiring intubation, only 25% were alive 3 months later. Despite good initial response to steroids in PCP and respiratory failure, survival remains limited. Controlled trials are needed to define better the role of steroid treatment in these patients.

Staphylococcus epidermidis extracted slime inhibits the antimicrobial action of glycopeptide antibiotics.

Certain strains of Staphylococcus epidermidis produce a mucoid slime that appears to be an important virulence factor. After crude slime was isolated from selected strains of S. epidermidis, phenol and chloroform were used to remove proteins and lipids. The remaining extract contained a polysaccharide that was seen on SDS gels stained with Stains-all. This extract was an inhibitor of the antimicrobial action of vancomycin, raising the minimum inhibitory concentration (MIC) to vancomycin in all 18 isolates of S. epidermidis. A dose-response curve was seen between the amount of extract added and the degree of resistance, as measured by both MIC and growth curves. A similar effect was noted with MICs of organisms to teicoplanin. Addition of the extract did not change the MIC to LY146032, although a modest effect on growth rate was observed. The extract did not raise the MIC to clindamycin, rifampin, and cefazolin. The extract reversed the synergism seen between vancomycin and gentamicin in the 5 strains tested in time-kill studies. The interference by slime of the antimicrobial effect of vancomycin and teicoplanin may explain why these antibiotics are sometimes ineffective in eradicating foreign body infections due to slime-producing coagulase-negative staphylococci.

Antipsoriatic effects of zidovudine in human immunodeficiency virus-associated psoriasis.

Four patients with psoriasis complicating human immunodeficiency virus (HIV) infection showed marked improvement in their psoriasis after being treated with oral zidovudine. The antipsoriatic effect persisted in two patients in spite of worsening helper T cell depletion. The antipsoriatic effect appeared to be dose-dependent and was associated with the development of erythrocyte macrocytosis, a known side effect of zidovudine. Zidovudine is useful for the therapy of HIV-associated psoriasis and should be tested for efficacy in non-HIV-associated psoriasis.