Age of first exposure to American football and long-term neuropsychiatric and cognitive outcomes.

Previous research suggests that age of first exposure (AFE) to football before age 12 may have long-term clinical implications; however, this relationship has only been examined in small samples of former professional football players. We examined the association between AFE to football and behavior, mood and cognition in a large cohort of former amateur and professional football players. The sample included 214 former football players without other contact sport history. Participants completed the Brief Test of Adult Cognition by Telephone (BTACT), and self-reported measures of executive function and behavioral regulation (Behavior Rating Inventory of Executive Function-Adult Version Metacognition Index (MI), Behavioral Regulation Index (BRI)), depression (Center for Epidemiologic Studies Depression Scale (CES-D)) and apathy (Apathy Evaluation Scale (AES)). Outcomes were continuous and dichotomized as clinically impaired. AFE was dichotomized into <12 and ⩾12, and examined continuously. Multivariate mixed-effect regressions controlling for age, education and duration of play showed AFE to football before age 12 corresponded with >2 × increased odds for clinically impaired scores on all measures but BTACT: (odds ratio (OR), 95% confidence interval (CI): BRI, 2.16,1.19-3.91; MI, 2.10,1.17-3.76; CES-D, 3.08,1.65-5.76; AES, 2.39,1.32-4.32). Younger AFE predicted increased odds for clinical impairment on the AES (OR, 95% CI: 0.86, 0.76-0.97) and CES-D (OR, 95% CI: 0.85, 0.74-0.97). There was no interaction between AFE and highest level of play. Younger AFE to football, before age 12 in particular, was associated with increased odds for impairment in self-reported neuropsychiatric and executive function in 214 former American football players. Longitudinal studies will inform youth football policy and safety decisions.

Effects of sarafloxacin hydrochloride on human enteric bacteria under simulated human gut conditions.

The effects of sarafloxacin, a newly developed veterinary fluoroquinolone antimicrobial, on 15 strains of aerobic and anaerobic bacteria of human origin were assessed under simulated human gut conditions. An in vitro gut simulation model was designed to mimic the situation of sarafloxacin (free and bound to meat) passing through the human gastrointestinal tract. The survival of bacteria in the simulation model and any subsequent change in the sensitivity of isolates to sarafloxacin were measured. The inhibitory level of sarafloxacin for the tested bacteria was strain dependent. It appeared that in broth culture Escherichia coli isolates were sensitive to sarafloxacin concentrations 5-fold lower than the concentrations present in the simulated gut model, suggesting that sarafloxacin may be partially unavailable due to absorption to organic matter in the model. There was no significant observed change in the sarafloxacin sensitivity of the bacterial strains exposed to the compound in the model.

A-61827 (A-60969), a new fluoronaphthyridine with activity against both aerobic and anaerobic bacteria.

A-61827 (A-60969 is the hydrochloric salt of A-61827) is a new aryl-fluoronaphthyridine which is active against aerobic and anaerobic bacteria. The MICs of A-61827 for 90% of strains (MIC90) of staphylococci and streptococci were less than or equal to 1 microgram/ml and were generally 1 to 4 twofold dilutions less than those of ciprofloxacin for these bacteria. The MIC90S of A-61827 for members of the family Enterobacteriaceae and Pseudomonas aeruginosa were also less than or equal to 1 microgram/ml. Ciprofloxacin was 1 to 3 twofold dilutions more active than A-61827 against these gram-negative bacteria. Neisseria gonorrhoeae, Campylobacter jejuni, and Haemophilus influenzae were susceptible to less than 0.06 microgram of A-61827 per ml. The MIC90 of A-61827 for Legionella pneumophila was 0.25 microgram/ml. A-61827 was as potent or 1 to 2 twofold dilutions more potent than ciprofloxacin against these organisms. The MIC90 of A-61827 for all anaerobic bacteria was less than or equal to 4 micrograms/ml compared with less than or equal to 32 micrograms/ml for ciprofloxacin. In mouse protection tests, A-61827 was as active as ciprofloxacin against Escherichia coli, P. aeruginosa, and Salmonella typhimurium and 5 to 10 times more active than ciprofloxacin against Staphylococcus aureus and Streptococcus pyogenes. A-61827 was as active as ciprofloxacin against P. aeruginosa in a mouse pyelonephritis model and more active than ciprofloxacin and metronidazole in a mouse Bacteroides fragilis abscess model. After oral administration of 100 mg/kg to mice, the peak concentrations of A-61827 and ciprofloxacin in serum were 2.3 and 2.4 micrograms/ml and the half-lives in serum were 3.9 and 1.2 h, respectively.

The frequency of in-vitro resistance development to fluoroquinolones and the use of a murine pyelonephritis model to demonstrate selection of resistance in vivo.

The frequency of development of resistance to the fluoroquinolones in vitro was generally low with Escherichia coli (in the order of 10(-7) to less than 10(-9) and high with Pseudomonas aeruginosa (in the order of 10(-5) to 10(-7)). Susceptibility to the fluoroquinolones also decreased after serial transfer in increasing concentrations of the drug. Although the MICs for the resistant E. coli variants were higher than that of the parent organism, they were still susceptible to achievable serum concentrations of all the quinolones except nalidixic acid. On the other hand some of the P. aeruginosa variants selected for resistance were resistant to achievable serum concentrations of all the quinolones. When E. coli pyelonephritis in mice was treated with the fluoroquinolones, difloxacin, A-56620, and ciprofloxacin were more effective than norfloxacin and nalidixic acid in lowering viable bacterial counts in the kidneys. The susceptibility of E. coli isolated from kidneys of mice treated with the quinolones was the same as that of the parent strain. When P. aeruginosa pyelonephritis in mice was treated with the fluoroquinolones an initial reduction in the cell count was seen, followed by an increase in the number of resistant variants. The resistant variants differed in their colony morphology and cell envelope proteins. The levels of resistance for the P. aeruginosa variants ranged from a two- to a 64-fold increase in the MIC.

In vitro evaluation of A-56619 (difloxacin) and A-56620: new aryl-fluoroquinolones.

The in vitro antibacterial potencies of A-56619 and A-56620, two new aryl-fluoroquinolones, were compared with the potency of norfloxacin against a broad spectrum of organisms. Cefotaxime, aztreonam, piperacillin, imipenem, penicillin, and gentamicin were also tested for reference purposes. The MICs required to inhibit at least 90% of the strains tested ranged from 0.25 to 4 micrograms/ml for A-56619 and from 0.06 to 0.5 microgram/ml for A-56620 for members of the Enterobacteriaceae. A-56619 was generally twofold less potent and A-56620 was twofold more potent than norfloxacin against most aerobic gram-negative bacilli, including members of the Enterobacteriaceae and Pseudomonas aeruginosa. Against indole-positive Proteus, Morganella, Providencia rettgeri, and Serratia strains, A-56619 was at least 8- to 16-fold less potent than norfloxacin. A-56619 and A-56620 were four- to eightfold more potent than norfloxacin against Staphylococcus aureus and equally potent to fourfold more potent against Streptococcus species, Haemophilus influenzae, and Neisseria gonorrhoeae. The MICs of A-56619 and A-56620 were only slightly affected by increased inoculum size or by the addition of various cations at physiologic concentrations. A-56619 was three- to fivefold less active at pH 8.0 than at pH 6.5 or 7.2. A-56620 was twofold less active at pH 6.5 than at pH 8.0 or 7.2 against members of the Enterobacteriaceae and Pseudomonas aeruginosa; similar pH variations did not affect A-56620 activity against gram-positive cocci. The potencies of A-56619, A-56620, and norfloxacin were less in urine than in Mueller-Hinton broth; however, this effect was more pronounced with norfloxacin. Human serum at a concentration of 50% caused a 4- to 64- fold decrease in the potency of A-56619 and an average 4-fold decrease in the potency of A-56620, compared with no effect on the potency of norfloxacin. A-56619, A-56620, and norfloxacin were bactericidal and, at four times the MIC, reduced the viable cell counts of Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa by approximately 99.9% within 2 h. A-56619, A-56620, and norfloxacin showed no significant synergistic activity and no antagonism when they were aminoglycoside or beta-lactam antimicrobial agents.

Cefmenoxime: in vitro activity.

The in vitro activity of cefmenoxime (SCE-1365 or A-50912), a new semisynthetic cephalosporin antibiotic, was determined for a broad spectrum of 1,234 organisms isolated as part of a multiclinic study. The minimum inhibitory concentration (MIC) of cefmenoxime required to inhibit at least 90 percent of strains tested (MIC90) ranged from 0.12 to 8 micrograms/ml for Enterobacteriaceae. MIC90S were 0.015 and 0.06 microgram/ml for Streptococcus pneumoniae and S. pyogenes, respectively, and 4 micrograms/ml for Staphylococcus aureus. Group D streptococci were less susceptible. The MIC90 of cefmenoxime for Neisseria gonorrhoeae and Hemophilus influenzae was 0.06 microgram/ml. Cefmenoxime was less active against Pseudomonas aeruginosa, Acinetobacter species, and Bacteroides fragilis (MIC50 = 16 micrograms/ml).

Antimicrobial activity of cefmenoxime (SCE-1365).

The in vitro activity of cefmenoxime (SCE-1365 or A-50912), a new semisynthetic cephalosporin antibiotic, was compared with those of cefazolin, cefoxitin, and cefamandole against a broad spectrum of 486 organisms and with that of cefotaxime against 114 organisms. Cefmenoxime and cefotaxime exhibited nearly equivalent activities against those organisms tested and were the most active of these cephalosporins against all aerobic and facultative organisms except Staphylococcus aureus. The minimum inhibitory concentration (MIC) of cefmenoxime required to inhibit at least 90% of strains tested (MIC(90)) ranged from 0.06 to 8 mug/ml for the Enterobacteriaceae. The MIC(90)s for gram-positive cocci were 0.015 and 128 mug/ml with good activity against the gram-positive organisms. In addition, cefmenoxime activity was bactericidal and only slightly affected by differences in inoculum size. The combination of cefmenoxime and gentamicin was synergistic against 80% of the Enterobacteriaceae and 100% of P. aeruginosa strains tested. Development of resistance to cefmenoxime was slow or absent for organisms with low initial MICs but more rapid for those with higher initial MICs. Cefmenoxime exhibited good protective activity in mice infected with Escherichia coli, Enterobacter cloacae, Proteus mirabilis, Proteus vulgaris, or S. aureus but was less effective against P. aeruginosa.

Comparative antimicrobial activity of O-demethylfortimicin A, a derivative of fortimicin A.

The in vitro antimicrobial activity of O-demethylfortimicin A (ODMF), a derivative of fortimicin A, was compared with those of fortimicin A and gentamicin against a spectrum of 256 organisms. All three antibiotics were active in low concentrations against all strains of Enterobacteriaceae, Acinetobacter sp., and Staphylococcus aureus, with ODMF most active against Proteus mirabilis, indole-positive Proteus, and Providencia and gentamicin most active against other species. Activity of each of the antibiotics against group D streptococci was poor. The overall activity of ODMF was superior to that of fortimicin A for all groups of organisms examined and was most pronounced, approximately three-fold, against strains of Pseudomonas aeruginosa. Both ODMF and fortimicin A were resistant to the action of several aminoglycoside-inactivating enzymes, with the exception of 3-N-acetyltransferase-I. ODMF and fortimicin A showed similar rapid bactericidal effects at multiples of the minimum inhibitory concentration and equivalent synergistic activity against enterococci when combined with penicillin G. The combination of carbenicillin with ODMF, fortimicin A, or gentamicin was synergistic for approximately 80% of the P. aeruginosa strains tested. Inactivation of ODMF and fortimicin A when combined with carbenicillin in vitro was minimal or absent, whereas gentamicin was substantially inactivated under similar conditions. ODMF, fortimicin A, and gentamicin exhibited protective activity in mice infected with Escherichia coli, Klebsiella pneumoniae, Proteus vulgaris, S. aureus, or P. aeruginosa. Gentamicin was the most active, followed by ODMF and fortimicin A. The superior in vitro activity of ODMF compared with fortimicin A against P. aeruginosa was confirmed in vivo.

Synthesis and antibacterial activity of 2'-substituted chelocardin analogues.

Chelocardin (1) was condensed with numerous hydrazines, hydrazides, and anilines, yielding 2'-substituted derivatives with antibacterial spectra similar to the parent antibiotic. The hydrazone derivatives 9 and 10 and the two anilino derivatives 42 and 44 had more in vivo antibacterial activity than chelocardin.

Treatment of otitis media caused by Hemophilus influenzae: evaluation of three antimicrobial regimens.

Ninety young children with otitis media, proven by tympanocentesis culture to be due to Hemophilus influenzae, were treated in a prospective double-blind study with one of three antimicrobial regimens: ampicillin, erythromycin ethylsuccinate, or erythromycin ethylsuccinate with concomitant trisulfapyrimidines. Results of efficacy evaluation indicated that the combination was as effective as ampicillin and statistically superior to erythromycine alone. Of the strains of H influenzae identified, 15/9 were typable with 12/9, type b. In vitro sensitivity tests indicated that the strains were sensitive to the amtimicrobials studied in clinically attainable levels; however, comparison of individual efficacy ratings with sensitivity results indicated that some children in each treatment group failed to respond as predicted.

Fortimicins A and B, new aminoglycoside antibiotics. IV. In vitro study of fortimicin A compared with other aminoglycosides.

The in vitro antimicrobial activity of fortimicin A, the most active member of the fortimicin complex, was compared with that of amikacin, gentamicin, sagamicin and tobramycin against 352 strains of Enterobacteriaceae and other medically significant organisms. Against most of these organisms fortimicin and amikacin had comparable levels of antimicrobial activity, generally slightly less than that of gentamicin, sagamicin or tobramycin. Fortimicin had relatively weak activity against Pseudomonas aeruginosa strains. Fortimicin shows many of the characteristics of other aminoglycoside antibiotics: (i) improved activity at alkaline pH, (ii) rapid, bactericidal action, (iii) reduced activity with increasing inoculum levels, and (iv) synergistic activity with penicillin against enterococci. The activity of fortimicin was compared to that of gentamicin, tobramycin and amikacin against a group of 95 naturally occurring, antibiotic-resistant Gram-negative bacilli other than Pseudomonas. The organisms were isolated from clinical sources and selected primarily for gentamicin resistance by the sensitivity disc test. Fortimicin showed excellent activity against this group of organisms. At a concentration of 6.2 mcg/ml, fortimicin inhibited the most strains (92.6%) followed by amikacin (90.5%), gentamicin (23.2%) and tobramycin (8.4%).

Inhibitory effect of light on growth-supporting properties of eosin methylene blue agar.

Exposure of eosin methylene blue agar to visible light can alter the ability of that medium to support microbial growth. Proteus species were most sensitive to the photodynamic action.

Microbiological study of water-softener resins.

Microbial identification using effluents backflushed from exhausted urban and rural tank resins and cleaned resins containing the sulfonated copolymer of styrene and divinylbenzene (SDB) were completed, along with microbial assessment of the concentrated stock salt brine. Forty-four different bacterial and fungal genera were identified. Extensive biochemical and animal virulence tests completed on one of the six bacterial salt brine isolates indicated a pathogenic staphylococcal strain. The retention of Staphylococcus aureus, a Flavobacterium sp, and Escherichia coli B bacteriophage was demonstrated both by using the nonexhausted sodium-regenerated resin and by using the same resin exchanged with different mono-, di-, and trivalent cations. Effluent counts completed after bacterial seepage through the resins indicated the Pb(++) exchanged resin removed 55% of the bacteria; Na(+), Fe(++), and Al(+++) removed 31 to 36% and Ca(++) and Cu(++) removed about 10 to 15%. Seventy per cent or more of the bacteriophage was removed by Fe(++), Cu(++), and Al(+++), whereas the Ca(++) and Na(++) cations removed 25 to 31%. Over a 77-day period, nonsterile tap water was passed through bacterial seeded and uninoculated SDB (Na) resin columns. Effluent and resin elution counts demonstrated the growth and survival of 2 different bacteria per column. Increased bacterial retention, survival, and multiplication occurred concomitantly with accumulation of organic and inorganic materials and the Ca(++) and Mg(++) cations from the tap water. Furthermore, microbial elution from resin particles taken from column depths of 1, 8, and 16 cm indicated a bacterial diminution with increasing depths.