Factors associated with falling asleep at the wheel among long-distance truck drivers.

Data on the prevalence and hypothesized predictors of falling asleep while driving were gathered through face-to-face interviews with 593 long-distance truck drivers randomly selected at public and private rest areas and routine roadside truck safety inspections. Hypothesized predictor variables related to drivers' typical work and rest patterns, extent of daytime and night-time drowsiness, symptoms of sleep disorder, measures of driving exposure, and demographic characteristics. A sizeable proportion of long-distance truck drivers reported falling asleep at the wheel of the truck: 47.1% of the survey respondents had ever fallen asleep at the wheel of a truck, and 25.4% had fallen asleep at the wheel in the past year. Factor analysis reduced the large set of predictors to six underlying, independent factors: greater daytime sleepiness; more arduous schedules, with more hours of work and fewer hours off-duty; older, more experienced drivers; shorter, poorer sleep on road; symptoms of sleep disorder; and greater tendency to night-time drowsy driving. Based on multivariate logistic regression, all six factors were predictive of self-reported falling asleep at the wheel. Falling asleep was also associated with not having been alerted by driving over shoulder rumble strips. The results suggest that countermeasures that limit drivers' work hours and enable drivers to get adequate rest and that identify drivers with sleep disorders are appropriate methods to reduce sleepiness-related driving by truck drivers.

The scope and nature of the drowsy driving problem in New York State.

A telephone survey was conducted of a random sample of New York State licensed drivers to determine the prevalence and circumstances of drowsy driving. Based on the survey responses, 54.6% of the drivers had driven while drowsy within the past year; 22.6% had ever fallen asleep at the wheel without having a crash, 2.8% had ever crashed when they fell asleep, and 1.9% had crashed when driving while drowsy. Of the reported crashes due to driving while drowsy or falling asleep at the wheel, 82.5% involved the driver alone in the vehicle, 60.0% occurred between 11:00 p.m. and 7:00 a.m. 47.5% were drive-off-road crashes, and 40.0% occurred on a highway or expressway. Multiple regression analysis suggested that the following driver variables are predictive of an increased frequency of driving drowsy: demographic characteristics (younger drivers, more education, and men); sleep patterns (fewer hours of sleep at night and greater frequency of trouble staying awake during the day); work patterns (greater frequency of driving for job and working rotating shifts); and driving patterns (greater number of miles driven annually and fewer number of hours a person can drive before becoming drowsy).

Synergy with cefsulodin or piperacillin and three aminoglycosides or aztreonam against aminoglycoside resistant strains of Pseudomonas aeruginosa.

Fifty-one strains of Pseudomonas aeruginosa, with resistance to one or more amino-glycosides, were tested for synergy with cefsulodin or piperacillin plus amikacin, tobramycin, gentamicin or aztreonam by the agar dilution technique. Cefsulodin plus any one of the three aminoglycosides regardless of the degree of resistance to the aminoglycoside was synergistic against P. aeruginosa for two thirds of the isolates. In contrast, synergy rates with piperacillin were much less uniform. The highest rate of synergy with piperacillin (90.0%) was observed with gentamicin for the gentamicin resistant strains. The lowest rate of synergy was observed with piperacillin plus amikacin (32.2%) for isolates with moderate resistance to amikacin. Synergy for strains with moderate resistance to amikacin was observed more commonly with cefsulodin than with piperacillin. Synergy for strains with a known mechanism of resistance to amikacin was more common with cefsulodin regardless of the mechanism of resistance. Cefsulodin or piperacillin in combination with aztreonam was rarely synergistic (less than 12%).

Antimicrobial effect of clindamycin in combination with aztreonam or aminoglycosides against Klebsiella spp.

The antimicrobial effect of clindamycin combined with aztreonam or an aminoglycoside (gentamicin, tobramycin or amikacin) was studied against 84 strains of Klebsiella pneumoniae and 18 strains of K. oxytoca with an agar dilution technique. Clindamycin concentrations of 1-20 mg/l and an inoculum of 10(4) cuf/spot were used. Anaerobic incubation of agar plates was associated with an increase in the MIC of aminoglycosides and no change or a decrease in the MIC of aztreonam. Lower concentrations of clindamycin (1-2 mg/l) were associated with a decrease in the MIC of aztreonam for 18% and an increase in the MIC of aminoglycosides for between 7% and 44% of the strains, depending upon the precise concentration used. However, higher concentrations of clindamycin (10-20 mg/l) were associated with a decrease in the MIC of aztreonam for between 36 and 87% and an increase in the MIC of aminoglycosides for between 13 and 64% of the isolates. These observations could be important when treatment plans for mixed aerobic/anaerobic infections including mixed Klebsiella spp. are considered.

Isolation and characterization of a transposon-induced cytotoxin-deficient mutant of Pseudomonas aeruginosa.

In order to provide a better system for investigating the role of cytotoxin in pathogenesis, we mutated wild-type Pseudomonas aeruginosa PA158 by introducing a transposon. The resulting pool of mutants was screened for cytotoxin-deficient strains. One mutant strain, PA114F5, was compared with PA158. Except for cytotoxin production and antibiotic resistance (specified by the transposon), the two strains appear isogenic. This mutant strain should be useful in further clarifying the role of cytotoxin in pathogenesis.

The effect of rifampicin on the in-vitro activity of cefpirome or ceftazidime in combination with aminoglycosides against Pseudomonas aeruginosa.

The in-vitro activity of cefpirome and ceftazidime when combined with aminoglycosides (gentamicin, amikacin, and tobramycin) in the presence and in the absence of rifampicin was evaluated against 32 isolates of Pseudomonas aeruginosa by two methods. Agar dilution susceptibilities demonstrated a marked reduction in synergy (FIC less than or equal to 0.5) when rifampicin was added to the combination. Synergy rates decreased from 59.4-84.4% without to 3.1-9.4% with the addition of rifampicin. In contrast, kill curve tests performed on two P. aeruginosa strains demonstrated synergy at 24 h when rifampicin was added to cefpirome, ceftazidime, gentamicin or a beta-lactam agent plus gentamicin combination. The addition of rifampicin to the combinations of cefpirome or ceftazidime plus gentamicin achieved a 2-log10 lower bacterial count at 24 h than that of the beta-lactam and gentamicin combination alone. When rifampicin was added to the combination cefpirome or ceftazidime plus gentamicin at different times during incubation, a greater bactericidal effect was observed when rifampicin was added at 0 and 1 h of incubation than when added later. No antagonism was observed with rifampicin when used in combination with beta-lactam agents and/or aminoglycosides.

Oropharyngeal and fecal carriage of Pseudomonas aeruginosa in hospital patients.

This prospective study was designed to determine the incidence of rectal and/or oropharyngeal colonization rates of patients with Pseudomonas aeruginosa upon admission to a general hospital and the risk of becoming colonized while hospitalized. Consecutive 186 admissions (180 patients) to one medical ward, one surgical ward, and the intensive care unit were studied over a period of 5 months. Rectal and oropharyngeal swabs for P. aeruginosa were obtained on admission, weekly thereafter, and/or upon discharge. Forty-two patients (22.6%) were colonized on admission, 20 patients (10.8%) acquired P. aeruginosa during hospitalization. Colonization on admission was observed twice as frequently on the surgical ward and in the intensive care unit as on the medical ward. Positive rectal cultures were more frequent than oropharyngeal cultures throughout the study (P less than 0.01). For patients admitted culture positive or culture negative, the probabilities of remaining culture positive or culture negative, respectively, remained at 44 and 72% after 35 days of hospitalization. The most common P. aeruginosa serotypes were 1, 6, and 10, and pyocin types 1, 3, and 10 were predominant. There was no statistical difference in the serotypes or pyocin types detected on admission or acquired during hospitalization. Except for two hospital-acquired first isolates which were resistant to moxalactam, all first isolates were susceptible to the four antibiotics tested. During the study, one isolate became resistant to azlocillin, gentamicin, and tobramycin, while two isolates became resistant to moxalactam. A statistical analysis was performed for 13 risk factors for all colonized and noncolonized patients. Colonization detected at the time admission was positively associated with age ( > 65 years), previous surgery of the gastrointestinal tract for neoplasm, and anemia ( P< 0.05). In contrast, for patients who entered the study culture negative, none of the analyzed 13 risk factors was associated with an increased probability for colonization. This observation included the administration of antimicrobial agents singly or in combination or both.

Susceptibility of Legionella pneumophila to eight antimicrobial agents including four macrolides under different assay conditions.

A comparison of agar dilution and microdilution susceptibility testing for eight antimicrobial agents, including roxithromycin, was performed against 48 isolates of Legionella pneumophila. For agar dilution tests, charcoal free agar (BSYE) and charcoal supplemented agar (BCYE) were used. In general, BSYE agar produced lower MICs than BCYE agar, except for imipenem. Microdilution testing data fell between the data obtained for the two agar media. The MBCs were two to sixteen fold higher than the MICs. Prolongation of the incubation time from 48 h to 72 h or growth in 5% CO2 did not influence the results. As tested by the microdilution method, an increase in the inoculum from 10(5) to 10(7) was associated with a two-fold increase in the MIC. Roxithromycin and two other investigational macrolides (A-56268 and rosaramicin) demonstrated better in-vitro activity than erythromycin.

Human granulocyte activity against moxalactam-induced filamentous forms of Pseudomonas aeruginosa.

The purpose of this investigation was to study the kinetics of human granulocyte (polymorphonuclear leukocyte) phagocytosis and bactericidal activity against beta-lactam antibiotic (moxalactam)-induced filamentous bacterial forms of Pseudomonas aeruginosa. Ultrastructural observations of rod and filamentous forms of P. aeruginosa and their interaction with polymorphonuclear leukocytes are presented. Growth of P. aeruginosa 1348A in the presence of 4 micrograms of moxalactam per ml (one-fourth the MIC) resulted in filamentous forms. Phagocytosis of 75Se-radiolabeled filaments was more efficient than that of rods during the first 20 min of the assay; subsequently, phagocytosis of both forms was equal. The polymorphonuclear leukocyte bactericidal activities against both forms, which were standardized to equal bacterial particle and viable-cell counts, were equivalent. Considering the greater size and mass of filaments compared with those of rods, we concluded that filaments are more susceptible to both phagocytosis and killing than are bacillary forms.

In vitro activities of PD 117,596 and reference antibiotics against 448 clinical bacterial strains.

The in vitro activity of PD 117,596, a new fluoroquinolone antibiotic, was tested against 448 bacterial isolates (15 genera) by agar dilution (inoculum, 10(4) CFU per spot). The activity of PD 117,596 was compared with that of 15 antibiotics against 327 gram-negative strains and with that of 8 other antibiotics against 121 gram-positive strains. PD 117,596 demonstrated the best activity against Klebsiella spp., Enterobacter spp., Acinetobacter spp., Serratia marcescens, and Branhamella catarrhalis (MICs for 90% of the isolates [MIC90S], 0.008 to 0.25 microgram/ml). PD 117,596 (MIC90, 0.25 microgram/ml) was at least twofold more active than ciprofloxacin against Pseudomonas aeruginosa and Pseudomonas spp. PD 117,596 and ciprofloxacin were similar in activity against Escherichia coli, Proteus mirabilis, Haemophilus influenzae, H. parainfluenzae, Neisseria gonorrhoeae, Legionella pneumophila, and Campylobacter jejuni (MIC90, 0.002 to 0.125 microgram/ml). PD 117,596 was more active than ciprofloxacin against streptococcal groups A, B, C, and G, S. pneumoniae, and enterococci (MIC90S, 0.06 to 0.125 microgram/ml). Against Staphylococcus aureus, including methicillin-resistant isolates, PD 117,596 (MIC90S, 0.03 to 0.06 microgram/ml) was 4- to 16-fold more active than ciprofloxacin and was most active against Corynebacterium spp. PD 117,596 appears to be the most active fluoroquinolone to date, with excellent activity against gram-positive bacteria and enhanced activity against gram-negative aerobic-facultative bacteria.

Comparative in-vitro activities of A-56268 (TE-031) and erythromycin against 306 clinical isolates.

The inhibitory (MIC) and bactericidal (MBC) activities of a new macrolide A-56268 (TE-031) against 306 clinical aerobic bacterial isolates was compared with that of erythromycin. The MIC90/MBC90 ratios for A-56268 were: Campylobacter jejuni 4/16, Haemophilus influenzae 8/8-16, H. parainfluenzae 8/8-16, Legionella pneumophila 0.06/0.5, methicillin-sensitive isolates of Staphylococcus aureus 0.5/1, and coagulase negative staphylococci 1/8, methicillin resistant isolates of Staph. aureus and coagulase negative staphylococci greater than 16/ greater than 16, Streptococcus pneumoniae 0.06/0.125, streptococcus Group A 0.06/2-4, streptococcus Group B 0.06/8- greater than 16, streptococcus Groups C and G 0.125/8 and Str. faecalis 4/64. Compared with erythromycin, A-56268 had greater inhibitory and bactericidal activity against isolates of L. pneumophila, with an MIC90 16-fold less and an MBC90 eight-fold less than that of erythromycin. Except for enterococci, A-56268 showed inhibitory activity equal to or greater than that of penicillin G against isolates of streptococci and an MIC two-fold less than that of erythromycin. For other strains tested, the inhibitory and bactericidal activities of A-56268 and erythromycin were similar. The clinical importance of the differences between these two macrolides will depend on the pharmacokinetic and tissue penetration properties of the new compound.

Bacteremia in patients undergoing oral procedures. Study following parenteral antimicrobial prophylaxis as recommended by the American Heart Association, 1977.

The type and rate of bacteremia following dental extractions, dental cleaning, or other dental/oral surgical procedures were studied in 124 patients with valvular heart disease following parenteral antibiotic prophylaxis (penicillin G potassium with or without streptomycin sulfate, or vancomycin hydrochloride) as recommended by the American Heart Association in 1977. Generally, under penicillin G prophylaxis with or without streptomycin, detection of bacteremia in blood culture media containing no penicillinase was low (14.7% to 16.1% at five minutes and 3.1% to 9.0% at 30 minutes after the procedure). The number and types of organisms recovered from patients who received penicillin prophylaxis alone or with streptomycin were similar. Anaerobes were recovered twice as frequently as aerobes. Polymicrobial bacteremia was rare and only one patient had streptococci detected in the blood culture. Addition of penicillinase to one blood culture medium, however, and comparing it with a similar medium without penicillinase was accompanied with a sixfold greater recovery from patients of both aerobic and anaerobic bacteria, including six patients with streptococcal bacteremia. Vancomycin prophylaxis was accompanied with bacteremia in only one patient.

The effect of diabetes mellitus on chemotactic and bactericidal activity of human polymorphonuclear leukocytes.

We studied the bactericidal activity (against P. aeruginosa) and chemotactic ability of polymorphonuclear leukocytes from 26 diabetic patients in three treatment groups (oral hypoglycemic, daily insulin, and continuous insulin infusion). Patients were studied before entry into intensified management protocols, and after intensified management in 11 of the 26 patients. Diabetic serum had a persistent inhibitory effect on both diabetic and normal white cells, but normal serum was unable to fully correct diabetic white cell killing to control values. After intensified management of diabetes, there was an improvement in bactericidal function of diabetic patient white cells, but not in the effect of diabetic serum. Diabetic serum, and to a lesser extent diabetic white blood cells, are defective mediators of killing of P. aeruginosa. Chemotaxis was normal in all patient groups. These findings confirm the earlier work of others showing that some patients with diabetes mellitus have a defect in host defense against infection with bacteria.

Production of cytotoxin by clinical strains of Pseudomonas aeruginosa.

Presence of cytotoxin was studied in extracts of 57 strains of Pseudomonas aeruginosa (46 bacteremia, 4 environmental, and 7 Fisher immunotype), 10 Pseudomonas species, and 7 nonpseudomonas isolates. Cytotoxin was identified by Western immunoblot in extracts of all P. aeruginosa isolates. None of the Pseudomonas species or nonpseudomonas isolates were shown to produce this protein. No immunologic cross-reactivity was observed between cytotoxin antibody and P. aeruginosa alkaline protease, toxin A, or elastase. In partially purified extracts of two bacteremia strains and PA 158 (parent strain for cytotoxin production), detection of cytotoxin by Western immunoblot was correlated with biological activity, as measured by the cell swelling assay. Cytotoxin appears to be produced by all strains of P. aeruginosa and biological activity can be demonstrated in extracts of the strains tested. This biological activity is neutralized by specific antibody. Because of its known marked cytotoxic effect on most eukaryotic cells, P. aeruginosa cytotoxin might be an important factor in the pathogenesis of P. aeruginosa infections.

Effects of storage and incubation conditions on human granulocyte phagocytic, bactericidal, and chemotactic functions.

This study was undertaken to determine the effects of different incubation conditions on human granulocyte (PMN) bactericidal, phagocytic, and chemotactic functions. Specifically, (1) how long may a patient's blood be held before assay and maintain original PMN function, and (2) how long may isolated PMNs be incubated for the purpose of exposure to various agents and still maintain original function? PMNs isolated following storage of whole heparinized blood at 4 degrees C for 24 and 48 hr phagocytized as well as fresh cells and their bactericidal activity was 96 and 85% of control values after 24 and 48 hr, respectively. Chemotaxis decreased to 62% of control after 24 hr. The bactericidal capacity of isolated PMNs stored at 4 degrees C for 24, 48, and 72 hr decreased to 85, 81, and 78% of controls, respectively. Phagocytosis after 24 hr storage was equal to controls. Chemotaxis was decreased to 59 and 34% of controls after 24 and 48 hr, respectively. Isolated PMNs incubated at 37 degrees C demonstrated impairment in phagocytic capacity after only 4 hr.

Comparison of the effect of three adrenal corticosteroids on human granulocyte function against Pseudomonas aeruginosa.

The effect of hydrocortisone, methylprednisolone, and dexamethasone on the phagocytic and bactericidal capabilities of normal human granulocytes (PMN) was studied under previously described optimal conditions for Pseudomonas aeruginosa, PA 1348A. At hydrocortisone and methylprednisolone concentrations of 1,000 micrograms/ml, delayed phagocytosis was clearly observed, whereas dexamethasone 400 micrograms/ml had no effect on phagocytosis. The bactericidal effect of PMN on PA 1348A was significantly reduced by all three corticosteroids at highest concentrations (p less than 0.05). However, the effect of methylprednisolone was greatest and that of dexamethasone was least evident, 25% and 10% reduction in PMN bactericidal activity, respectively. Following exposure to the highest concentrations of corticosteroids, TEM observations correlated well with the PMN functional assays. While the observations of PMN and bacteria in controls, hydrocortisone, and dexamethasone preparations were similar, evidence for incomplete phagocytosis, lack of vacuole coalescence, minimal disruption of bacterial cell walls, and dividing bacteria in phagosomes were evident in methylprednisolone preparations. These PMN functional and TEM observations suggest that of the three corticosteroids studied, methylprednisolone appears most deleterious to the PMN phagocytic and bactericidal activity.

In vitro activity of CI-934 and other antimicrobial agents against gram-positive and gram-negative bacteria.

The activity of CI-934, a new carboxy-quinolone antibiotic, against gram-positive cocci and bacilli and gram-negative bacilli was compared with that of reference antibiotics. CI-934 demonstrated excellent activity against gram-positive organisms, including Corynebacterium sp. In addition, although the activity of CI-934 against gram-negative bacilli was less than that reported for similar agents, it was comparable to that of aminoglycosidic aminocyclitol antibiotics.

Effects of Pseudomonas aeruginosa cytotoxin on human serum and granulocytes and their microbicidal, phagocytic, and chemotactic functions.

The effect of Pseudomonas aeruginosa cytotoxin on human granulocytes (PMNs) and pooled human serum was studied by hemacytometer counts, phagocytic, bactericidal, and chemotaxis assays, and by transmission electron microscopy. The optimal assay conditions for phagocytosis of 75Se-labeled P. aeruginosa 1348A included 20% pooled human serum and a ratio of one PMN to between 10 and 20 bacteria. For the bactericidal assay, 20% pooled human serum and a ratio of one PMN to between one and five bacteria were used. Chemotaxis of PMNs was studied by agarose gel technique with 10(-7) M f-Met-Leu-Phe or 0.01 to 35 micrograms of cytotoxin per ml as a chemoattractant. The degree of PMN destruction was dependent on cytotoxin concentrations and PMN exposure time to cytotoxin. Virtually complete PMN lysis was observed after a 2-h exposure to 6 to 10 micrograms of cytotoxin per ml. PMN exposure to 2 micrograms of cytotoxin per ml for as long as 2 h had no adverse effect on phagocytosis. PMN exposure to greater than or equal to 4 micrograms of cytotoxin per ml for 2 h demonstrated a significant decrease in the percentage of bacteria killed. The results of experiments designed to separate cytotoxin effect on PMN lysis from the effect on PMN bactericidal capacity showed that there is an effect of cytotoxin on PMN bactericidal function. PMN exposure to 4 micrograms of cytotoxin per ml for 30 min caused a significant decrease in PMN migration. Cytotoxin had no chemoattractant qualities or effect on pooled human serum as studied by chemotaxis and phagocytosis assays. Although a cytotoxin concentration of greater than or equal to 2 micrograms/ml was required to demonstrate PMN ultrastructural changes observed in transmission electron microscopy studies, at a concentration of 0.1 microgram/ml, cytotoxin caused an impairment in the integrity of the PMN membrane, allowing a low-molecular-weight substance (ruthenium red) to enter into the cytoplasm. Cytotoxin may be an important factor in the pathogenesis and in the high mortality rate of patients with P. aeruginosa infections.

Pharmacokinetics of moxalactam in elderly subjects.

The pharmacokinetics of moxalactam were studied in 19 male volunteers 60 years of age or older with normal liver function tests and a creatinine clearance of greater than or equal to 60 ml/min. Moxalactam was administered in single or multiple intravenous or intramuscular doses. Rapid and complete intramuscular bioavailability was demonstrated in a subgroup of the study population. The mean plasma half-life was 2.9 +/- 0.8 h for intravenous doses and 3.5 +/- 0.9 h for intramuscular doses. Average renal clearances of 0.04 liters/kg per h accounted for 74.0 +/- 15.0% of total plasma clearance. Moxalactam plasma clearance showed a statistically significant (P less than 0.01) correlation with measured and calculated creatinine clearance. The major differences in moxalactam pharmacokinetics seen in the elderly appear to be related to diminishing renal function and highly variable nonrenal elimination. Creatinine clearance can be used in estimating moxalactam doses in the elderly without significant renal impairment, but recommendations for the use of serum creatinine as an estimation of renal function or drug half-life are not valid in this population group.

Bacteremia due to Pseudomonas aeruginosa: use of a combined typing system in an eight-year study.

P aeruginosa bacteremia is a nosocomial disease with a high mortality occurring in colonized, debilitated, and leukopenic patients and in those receiving immunosuppressive and antimicrobial agents [2]. Outbreaks of P aeruginosa bacteremia have often been associated with environmental reservoirs [3]. The 190 strains of P aeruginosa described in this study represent single isolates from bacteremic patients during an eight-year period. Representing about 50% of total isolates, the most common pyocin types were 1b, 3, and 10, immunotypes 1, 2, and 3 + 7, and serotypes 11, 6, and 1. Of the 37 known pyocin types, only 10 were represented in this study. All seven immunotypes and 14 of 17 serotypes were found. The overall typability for each of the three techniques was 88%-90%; however, the largest numbers of typable patterns were found when all three typing methods or pyocin and either immunotyping or serotyping were used. The smallest number of typing patterns occurred when immunotyping and serotyping were performed together. Correlation among the following types was greater than 50%; pyo 3:immuno 1:sero 6; pyo 10:immuno 2:sero 11, and pyo NI:immuno 4:sero 1. Upon repeated testing the reproducibility of types for each technique was 98%-100%. For the most precise epidemiologic studies of P aeruginosa infections all three typing methods should be employed.