Health care worker exposure to HIV-1 and HTLV I-II in critically ill, resuscitated emergency department patients.

STUDY OBJECTIVE: Exposure to HIV-1 is of profound concern to health care workers. HTLV-I and HTLV-II, retroviruses with similar modes of transmission as HIV-1, also cause disease in human beings. Emergency department resuscitations are high-risk situations for such exposure. The purpose was to determine the seroprevalence of HIV-1 and HTLV I-II in patients undergoing ED resuscitations, the magnitude of health care worker exposure, and risk factors associated with infection. DESIGN: Prospective identity-unlinked seroepidemiologic study. SETTING: ED of a 950-bed private inner-city teaching hospital. Participants included 370 patients undergoing ED resuscitations. MEASUREMENTS: Serum was tested for antibodies to HIV-1 and HTLV I-II. Questionnaires were completed by the physician in charge of the ED resuscitations. RESULTS: Fifteen (4.1%) (95% confidence interval [CI], 2.1% to 6.1%) patients were HIV-1 seropositive, and seven (1.9%) (95% CI, 0.7% to 3.1%) were HTLV I-II positive. Eleven (5.6%) (95% CI, 2.4% to 8.8%) of 197 trauma patients and 11 (6.4%) (95% CI, 2.8% to 10.0%) of 173 medical patients were infected with one of these viruses. Health care workers had direct cutaneous contact with patient blood during 114 (31%) ED resuscitations and with infected patient blood during 11 (3%) ED resuscitations. An additional 11 ED resuscitations involved parenteral exposures, one to HIV-1-infected blood. No factors could be identified that would quickly and reliably predict infection. CONCLUSION: Health care workers must protect themselves in such high-risk situations by strict compliance to mandatory universal precautions.

Filtration of dialysate using an on-line dialysate filter.

UNLABELLED: Increased concerns about pyrogenic contamination of dialysate have led to the development of an on-line dialysate filtration system. Bacteriological testing of the system was performed (n = 6) by introducing bicarbonate concentrate contaminated with E. coli 026:B 6 (3 x 10(9) cfu/ml) into a dialysis machine equipped with a two-stage polysulfone filtration system. The bacterial concentration of the dialysate entering the filtration system was maintained above 10(6) cfu/ml and endotoxin levels ranged from 30-300 ng/ml during the 3-hour test period. Bacterial and endotoxin levels on the input side of the first-stage filter reached minimum concentrations of 5.4 x 10(9) cfu/ml and 30,000 ng/ml respectively. All output samples of filtered dialysate showed no bacterial growth and endotoxin levels were below the sensitivity (0.003 ng/ml) of the LAL assay. A dialysis machine (QD = 500), equipped with a single stage filtration system, was used for 18 months of clinical testing. In order to evaluate the system's reliability with regard to membrane failures and reduced dialysate flow, filter membrane integrity was verified weekly using a pressure holding test and dialysate flow was measured under routine clinical conditions. No membrane failures occurred, and dialysate flow was maintained at 511 +/- 17 ml/min (n = 70) during the test period. IN CONCLUSION: dialysate filtration is an effective and practical method for prevention of pyrogenic reactions due to high levels of bacteria and endotoxins.

Comparison of five commercial western blot kits for detection of human immunodeficiency virus 1.

Twenty-two human immunodeficiency virus 1 (HIV-1) enzyme immunoassay (EIA) reactive and two non-reactive patient specimens were analyzed using five commercially available HIV-1 Western blot kits. The percentage of HIV-1 bands detected by each kit was recorded. The differences between pairs of kits were not found to be statistically significant at the 0.05 level. All EIA reactive specimens were reconfirmed as reactive by each Western blot kit tested.

Reduction in Legionella pneumophila through heat flushing followed by continuous supplemental chlorination of hospital hot water.

An increase in endemic rate of nosocomial Legionella pneumophila pneumonia prompted an investigation that revealed 16.2% (12/74) of patient care hot-water sites surveyed were culture-positive for L. pneumophila. No positive cultures were recovered from cooling towers, air intakes, or construction areas. Heat flushing of hospital hot-water outlets to temperatures greater than 60 degrees C for 30 min achieved a 66% reduction in positive Legionella cultures. After 4 1/2 months, different serotypes recurred in previously eradicated areas and there were new positive cultures. Continuous supplemental chlorination of the hot-water system (2 parts per million [ppm]) significantly reduced the number of culture-positive samples from 37.4% (43/115) to 7.0% (8/115) after 6 weeks (P less than .005). Of 30 sites surveyed 6 months after hot-water chlorination, 67% (20) were still culture-negative. Of those positive, 70% had less than or equal to 150 L. pneumophila/ml and 90% were from bathtubs. Adverse effects of chlorination on users and plumbing have not been seen. There have been no definite cases of nosocomial L. pneumophila in areas served by supplemental chlorine during the first 17 months of the chlorination project. Technology allowing tighter regulation of chlorine and use of silicates to control corrosion have made continuous hot-water chlorination a safe and effective option in Legionella control.

In-vitro susceptibility of staphylococci to fleroxacin in comparison with six other quinolones.

Susceptibilities of methicillin-resistant Staphylococcus aureus (MRSA, n = 32), methicillin-sensitive S. aureus (MSSA, n = 32), and S. epidermidis (SE, n = 24) were determined to fleroxacin, amifloxacin, ciprofloxacin, difloxacin, enoxacin, norfloxacin, and ofloxacin. All organisms were isolated from the blood of patients with infective endocarditis. MRSA and MSSA MIC90s were less than 1.0 mg/l of fleroxacin, ciprofloxacin, difloxacin, and ofloxacin while amifloxacin and norfloxacin produced MIC90s of less than 2.0 mg/l and enoxacin MIC90s of less than 4.0 mg/l. For S. epidermidis MIC90s were less than 1.0 mg/l of all quinolones except amifloxacin whose MIC90 was less than 2.0 mg/l. Two strains from each staphylococcal group were used in time-kill trials performed with all seven quinolones. Within 8 h, all quinolones colony counts were decreased by one log. At 24 h, most quinolones decreased MRSA, MSSA, and SE colony counts by two to four logs; however, exceptions were found with (1) difloxacin, enoxacin, and norfloxacin against MRSA, (2) ciprofloxacin and enoxacin against MSSA, and (3) ciprofloxacin against SE in which all colony counts increased one to three logs in 24 h. When quinolone time-kill trials did not show a decrease in colony counts at 24 h, the MIC's for the 24 h growth showed a four- to 250-fold increase when compared with pre-trial MICs. No selection or emergence of resistant organisms was found with fleroxacin, amifloxacin or ofloxacin.

Inhibition of Legionella pneumophila multiplication within human macrophages by fleroxacin.

The susceptibility of Legionella pneumophila to a new quinolone, fleroxacin, was studied in both an extra- and an intracellular system. The activity of fleroxacin was compared with that of erythromycin, cefoxitin, and rifampicin. In the extracellular system, erythromycin inhibited while cefoxitin killed the organism. Extracellularly, fleroxacin performed similarly to cefoxitin. Rifampicin was initially bactericidal for L. pneumophila but resistant bacteria emerged at 48 h. The Horwitz monocyte model was used for studies of intracellular antimicrobial activity. At ten times the MIC, cefoxitin did not inhibit intracellular L. pneumophila. Fleroxacin was as active as erythromycin and rifampicin in inhibiting intracellular L. pneumophila. No intracellular, rifampicin-resistant L. pneumophila emerged. Addition of rifampicin to cefoxotin, erythromycin or fleroxacin provided neither synergy nor antagonism.

Comparison of ciprofloxacin and rifampicin in experimental Legionella pneumophila pneumonia.

We evaluated intraperitoneal ciprofloxacin and rifampicin alone and as combination therapy in experimentally induced Legionella pneumophila pneumonia in guinea pigs. Intraperitoneal treatment began 48 h after intratracheal inoculation of 3 X 10(6) L. pneumophila and consisted of sterile saline (0.3 ml bid), ciprofloxacin (30 mg/kg bid), rifampicin (10 mg/kg/bid), or ciprofloxacin plus rifampicin (same doses). Animals were treated for five days and survivors killed after 11 days. Quantitative lung cultures were done post mortem. Respective mean and median days of animal survival were increased by treatment with ciprofloxacin plus rifampicin (8.4 and 9.5 days), ciprofloxacin (8.2 and 7.5 days), or rifampicin (8.3 and 7.5 days), compared with controls (5.5 and 5.0 days). Compared with control animals (log rank test) survival was improved by treatment with ciprofloxacin plus rifampicin (P less than or equal to 0.047) ciprofloxacin (P less than or equal to 0.047) or rifampicin (P less than or equal to 0.047). Quantitative lung cultures (cfu/g) were also decreased by treatment with ciprofloxacin plus rifampicin (2.0 X 10(4)), ciprofloxacin (5.4 X 10(4)), or rifampicin (1.7 X 10(4)) compared with controls (3.2 X 10(8)). No differences in survival, quantitative lung cultures, or animal weights were noted between treatment groups. This study demonstrates that ciprofloxacin is as effective as rifampicin in the treatment of experimentally induced L. pneumophila pneumonia and that the combination of ciprofloxacin plus rifampicin has no advantages over single agent therapy in this model.

Effect of quinolones and other antimicrobial agents on cell-associated Legionella pneumophila.

We evaluated the in vitro susceptibility of Legionella pneumophila ATCC 33152 (serogroup I) to 13 antibiotics alone and in combination with rifampin (0.1 mg/liter) by three methods. Extracellular susceptibility was determined by MIC determinations and time kill curves in buffered yeast extract broth, while intracellular susceptibility was determined by peripheral human monocytes in RPMI 1640 culture medium. Antibiotic concentrations equal to or greater than the broth dilution MIC inhibited or killed L. pneumophila by the time kill method, except this was not the case for trimethoprim-sulfamethoxazole. Antibiotic concentrations below the broth dilution MIC did not inhibit Legionella growth. The only antibiotic-rifampin combinations which produced improved killing of L. pneumophila by the time kill method were those in which the logarithmic growth of L. pneumophila occurred during the experiment (rosoxacin, amifloxacin, cinoxacin, trimethoprim-sulfamethoxazole, clindamycin, and doxycycline). Neither direct MICs nor time kill curve assays accurately predicted intracellular L. pneumophila susceptibility. Rifampin, erythromycin, ciprofloxacin, rosoxacin, enoxacin, amifloxacin, gentamicin, clindamycin, and doxycycline all inhibited intracellular L. pneumophila growth at readily achievable concentrations in serum. Cefoxitin and thienamycin showed no inhibition of growth, although they were present extracellularly at concentrations that were 20 to 1,000 times their broth dilution MICs. Clindamycin was the only antibiotic that was able to inhibit intracellular L. pneumophila growth at an extracellular concentration below its MIC. The gentamicin (5 mg/liter)-rifampin combination was the only antibiotic-rifampin combination which demonstrated decreased cell-associated Legionella survival in this model of in vitro susceptibility.

In-vitro susceptibility of gram-positive cocci to LY146032 teicoplanin, sodium fusidate, vancomycin, and rifampicin.

LY146032, a new antimicrobial agent with activity against Gram-positive cocci, was tested against methicillin-susceptible and methicillin-resistant Staphylococcus aureus, methicillin-susceptible and methicillin-resistant Staph. epidermidis, Staph. saprophyticus, and Streptococcus faecalis. MIC90s in cation-supplemented Mueller Hinton broth by the microdilution broth method were less than 1.0 mg/l for all organisms tested. Increasing or decreasing the inoculum size did not appreciably effect the MIC50 or MIC90 for any organism group nor did decreasing the incubation temperature. The addition of sodium chloride to the test system did not appreciably effect the susceptibility of methicillin-resistant Staph. aureus to LY146032. All organisms were 4 to 32 times more susceptible to LY146032 than to vancomycin. The Staph. aureus had LY146032 susceptibility patterns which were similar to those of teicoplanin and sodium fusidate. LY146032 was 4-16 times more active than teicoplanin against Staph. saprophyticus and Staph. epidermidis while teicoplanin was 8-16 times more active than LY146032 against Str. faecalis.

The in-vitro and in-vivo efficacy of cisplatin and analogues in the treatment of herpes simplex virus-II infections.

The antitumour effect of cisplatin results from cross-linking and disruption of DNA when it binds to DNA bases, especially cytosine and guanine. Since herpes simplex virus (HSV) has a high cytosine and guanine content, cisplatin might be expected to have an antiviral effect against HSV. The 50% inhibitory concentration of cisplatin for HSV-II was 0.06 mg/l. Six of ten platinum analogues had 50% inhibition of plaques at less than or equal to 10 mg/l. We evaluated the in-vivo activity of cisplatin against the MS strain of HSV-II in the mouse genital HSV model. Mice were treated either intraperitoneally or intravaginally beginning at 3 or 51 h after inoculation. In the intraperitoneally treated groups infection rates were lower, but not significantly; 4 of 15 in the 3-h and 7 of 15-h group, compared to 9 of 15 in the untreated control group (P greater than 0.18, chi-square test). Intravaginal cisplatin demonstrated a significant reduction of the infection rate from 10 of 15 untreated controls, compared to 5 of 18 in the 3-h and 5 of 17 in the 51-h group (P less than 0.05, chi-square test). No toxic effects of intravaginal cisplatin were seen in uninfected mice. These studies suggest that platinum containing drugs warrant further evaluation as a new class of antiviral agents with activity against HSV.

The effect of heat upon the interaction between aminoglycosides and semi-synthetic penicillins in human serum: a consideration for HIV infectious serum.

We conducted 2 experiments to study the effect of heat on the interaction between aminoglycosides and semi-synthetic penicillins in human serum. In one experiment, human serum spiked with either gentamicin or tobramycin at a concentration of 4.7 mg/l plus carbenicillin, ticarcillin, piperacillin, mezlocillin, or azlocillin at concentrations of either 50 mg/l or 150 mg/l was subjected to a 30-min, 56 degrees C waterbath incubation. In the second experiment, randomly selected sera from patients receiving either gentamicin or tobramycin were also heat-treated. Two methods, the Abbott TDx and the Syva Emit, were used for each aminoglycoside assay. The difference between pre- and post-heat treatment aminoglycoside concentration was less than 10% in approximately 92% of the patient sera and in 93% of the spiked sera containing an aminoglycoside plus a semi-synthetic penicillin at 50 mg/l. For sera spiked with an aminoglycoside plus a semi-synthetic penicillin at 150 mg/l, post-heat treatment concentrations were 5-19% lower than pre-heat treatment concentrations. In most instances, heat treatment of sera does not alter aminoglycoside concentrations to any clinically significant degree.

In vitro susceptibility of gram-positive cocci to paldimycin.

Paldimycin (U-70138F) is a new antimicrobial agent with activity against gram-positive cocci. Clinical isolates of staphylococci and streptococci were tested. MICs were higher in Mueller-Hinton broth than in nutrient broth. Change in pH had minimal effect on the MICs in either broth. When inoculum size was varied, an inoculum effect was observed. The gram-positive cocci tested were generally more susceptible to paldimycin than to vancomycin.

Lack of bacterial aerosols associated with heat and moisture exchangers.

Contaminated condensate might serve as a source for cross infection. Heat and moisture exchangers (HME) are devices that humidify inspired gases, which pass through a hygroscopic felt pad surrounded by a cellulose sponge housed in a plastic case. In our study, we used a Servo 150 HME in place of a cascade humidifier in mechanical ventilator circuits. We performed 2 studies to evaluate the microbiologic safety of the HME. First, 42 HMEs used by patients for 24 h were tested in the laboratory for contamination. To simulate patient/air exchange, the HMEs were connected to the Andersen Sampler (flow at 35 L/min x 20 min). Although the inner felt pad of the HMEs was contaminated in 74% of the units (31 of 42), only 4.8% (2 of 42) generated 1 to 2 bacteria/702 L of air. In a second study, HMEs contaminated with either Staphylococcus aureus or Pseudomonas aeruginosa (at 10(3), 10(5), or 10(8) organisms/ml) were connected to an Andersen Air Sampler to simulate a ventilator circuit. Bacterial aerosols were not generated, with the exception of 2 to 4 bacteria recovered after contamination with 10(8) bacteria. The HME can provide humidification for mechanically ventilated patients with little risk of generating respirable bacterial aerosols.

Failure of therapy in pseudomonas endocarditis: selection of resistant mutants.

Despite optimal use of available antibacterial agents, endocarditis due to Pseudomonas aeruginosa is commonly associated with poor response to medical treatment. Two patients are described in whom emergence of resistance to beta-lactam antibiotics was associated with clinical failure. A subpopulation of resistant mutants (10(-7)) was found within the initial, apparently sensitive population of bacteria. These resistant mutants were similar to posttherapy isolates in their increased production of beta-lactamase and in their identical pattern of resistance to beta-lactam antibiotics. Moreover, the only beta-lactamase produced was type Id, and this enhanced production proved to be constitutive. A relatively large inoculum (10(6) colony-forming units/g of tissue) of bacteria was found postoperatively in the heart valves of both patients. The failure to respond is postulated to be due to the selection of these producers of high levels of beta-lactamase in a large bacterial inoculum.

Single-dose cephalexin therapy for acute bacterial urinary tract infections and acute urethral syndrome with bladder bacteriuria.

The efficacy of single-dose therapy with 3 g of cephalexin was evaluated in 129 women with symptoms of acute uncomplicated lower urinary tract infections. Of 91 patients with significant bacteriuria, 61 (67%) were cured of their original infection; this was similar to the 54 to 79% cure rates reported in unselected populations of women of a wide age range treated for acute uncomplicated urinary tract infections with a single dose of amoxicillin or trimethoprim-sulfamethoxazole (J. Rosenstock, L. P. Smith, M. Gurney, K. Lee, W. G. Weinberg, J. N. Longfield, W. B. Tauber, and W. W. Karney, Antimicrob. Agents Chemother. 27:652-654, 1985; N. E. Tolkoff-Rubin, M. E. Wilson, P. Zuromskis, I. Jacoby, A. R. Martin, and R. H. Rubin, Antimicrob. Agents Chemother. 25:626-629, 1984). The cure rates of (87%) for our younger patients, those less than 25 years of age, was better than that (46%) for our patients over 40 years of age (P less than 0.001). Patients with infections that were negative in an antibody-coated bacteria test were cured at a significantly higher rate than those with infections that were positive in an antibody-coated bacteria test (71 versus 19%; P = 0.003). Those patients with infections caused by cephalexin-susceptible organisms were cured at a rate similar to that for patients with infections caused by cephalexin-resistant organisms (68 versus 50%; P = 0.62). The cure rate for suburban patients was 90%, versus 45% for inner-city patients (P = 0.008). Of the 28 women with acute urethral syndrome due to low-level bacteriuria, 27 were cured.

Serum and crevicular fluid concentrations after a single oral dose of metronidazole.

Previous studies have shown that metronidazole is an effective chemotherapeutic agent in the treatment of certain types of periodontal disease. The purpose of this study was to assess, over 18 hours, the concentration of the drug in serum and gingival crevicular fluid after a single oral dose. Six female volunteers with gingivitis created by cessation of brushing for 2 weeks, took 250 mg of metronidazole orally. Micropipettes were used to collect 20 microliters of serum and 4 to 5 microliters of gingival fluid hourly for 8 hours, and at the 12th and 18th hours. Samples were assayed with a high pressure liquid chromatograph. Mean drug levels in serum closely matched those reported by Stephen et al. (Br Dent J 7: 313, 1966) with polography. Mean serum drug levels peaked at 6.09 micrograms/ml at the 2nd hour, and mean gingival crevicular fluid drug levels peaked at 3.62 micrograms/ml at the 2nd and 7th hours. The drug was detectable in both fluids for up to 18 hours. Mean serum concentrations remained greater than mean gingival fluid concentrations at all time intervals, though the differences were not significant (P less than 0.05) as determined by a Hoteling's T2 test. Using reported minimal inhibitory concentration values of metronidazole for various periodontopathogens, it was concluded that a single oral dose of metronidazole will deliver potentially inhibitory levels of the drug to the periodontium in serum and in gingival crevicular fluid.

Evaluation of the sterility and stability of insulin from multidose vials used for prolonged periods.

Diabetic patients frequently use their insulin vials for prolonged periods, even though antibacterial preservatives used in multidose insulin vials are not required to be effective beyond 28 days. For this reason, we evaluated the antibacterial activity present in multidose insulin vials for up to 50 days. Multidose lente insulin vials were inoculated with S. aureus and P. aeruginosa. Vials incubated at room temperature (21 degrees C) were sterile by 48 hours, whereas when they were incubated at refrigerator temperatures (4 degrees C), S. aureus contamination persisted up to the 17th day and P. aeruginosa were killed after 10 days. The same vials were serially contaminated on days 17, 30, and 50, and a similar antibacterial effect was maintained. Sixty-nine multidose insulin vials used for an average of 53 days were cultured. Eight vials demonstrated bacterial contamination with 1 cfu/ml of S. epidermidis or Propionibacterium acnes. No endotoxin was detected in the multidose vials used for more than 28 days. Insulin assays on 40 multidose insulin vials used for more than 28 days showed an average insulin content of 101.6 +/- 1.9 units/ml. This study did not demonstrate significant bacterial contamination, endotoxin activity, or insulin degradation of multidose insulin in vials used for periods longer than 28 days. In addition, antibacterial preservatives were more effective at room temperature than at refrigerator temperature; thus, the practice of patients not refrigerating insulin vials is sensible.