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1.  Conjugational transfer of gentamicin resistance plasmids intra- and interspecifically in Staphylococcus aureus and Staphylococcus epidermidis. 
We have previously reported the transfer of gentamicin resistance (Gmr) plasmids in a mixed culture inter- and intraspecifically between strains of Staphylococcus aureus and Staphylococcus epidermidis isolated at Michael Reese Hospital (Jaffe et al., Antimicrob. Agents Chemother. 21:773-779, 1982). We have now shown that representatives of these plasmids were transferred between apparently nonlysogenic strains of S. aureus either in mixed culture in broth or by filter-mating on agar medium. The mechanism of transfer appeared to be conjugation. A transferable Gmr plasmid (pSH8) mobilized or cotransferred a tetracycline R-plasmid and a chloramphenicol R-plasmid that were not independently transferable. The transfer of Gmr plasmids was accompanied by a high incidence of deletion mutations with varied loss of plasmid resistance determinants and, with some mutants, loss of the ability to effect self-transfer. Restriction endonuclease digestion of pSH8 and its deletion mutants made it possible to assign the property of self-transfer to a specific segment of the pSH8 genome and provided the basis for a physical and genetic map of that plasmid. Similar Gmr plasmids from S. aureus strains isolated in locations remote from Michael Reese Hospital had resistance determinants and transfer properties comparable to those of pSH8. Our observations provide evidence for the conjugal transfer of some staphylococcal plasmids, apparently independent of the presence of phage. This mechanism may be of significance in the intra- and interspecific dissemination of resistance to aminoglycosides and other antibiotics in Staphylococcus spp.
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PMCID: PMC184633  PMID: 6219618
2.  In vitro activity of ceftriaxone alone and in combination with gentamicin, tobramycin, and amikacin against Pseudomonas aeruginosa. 
The in vitro activity of ceftriaxone alone and in combination with gentamicin, tobramycin, and amikacin against 50 Pseudomonas aeruginosa strains was studied by the broth dilution method and the time-kill curve method. The majority of the P. aeruginosa strains tested were resistant to ceftriaxone. Combining ceftriaxone with the aminoglycosides resulted in synergism, antagonism, or indifference.
PMCID: PMC185160  PMID: 6314890
3.  Cefoperazone pharmacokinetics in normal subjects and patients with cirrhosis. 
The pharmacokinetics of cefoperazone were studied and compared in six normal subjects and six patients with severe liver disease. All subjects received a 2-g intravenous infusion of cefoperazone over 15 min. Significantly different results were noted between normal subjects and patients with cirrhosis (range [mean]) for the following: peak serum concentrations (203 to 345 [239] versus 82 to 206 [141] micrograms/ml; P less than 0.01); serum beta half-lives (1.0 to 1.8 [1.5] versus 2.3 to 9.9 [4.5] h; P less than 0.05); renal excretion (17 to 27 [21] versus 32 to 60 [50]%; P less than 0.01); and apparent volumes of distribution at steady state (4.1 to 7.8 [6.3] versus 12.7 to 23.8 [15.9] liters/1.73 m2; P less than 0.01). Lower peak serum levels in the patients with cirrhosis were probably related to an increased apparent volume of distribution secondary to ascites and to decreased serum protein binding of cefoperazone. Longer beta half-lives in the patients with cirrhosis were probably secondary to both decreased hepatic excretion caused by severe liver disease and to increased apparent volume of distribution. However, the longest beta half-life among the patients with cirrhosis was in a subject with a serum creatinine level of 2.1 mg/dl. We conclude that, although mild to moderate impairment of cefoperazone excretion occurs in patients with hepatic disease, adjustment of dosage may be necessary only with concomitant renal insufficiency.
PMCID: PMC184657  PMID: 6221691
4.  Comparison of the concentrations of ceftazidime in the serum of newborn infants after intravenous and intramuscular administration. 
The concentrations of ceftazidime in serum were studied in 16 preterm and term neonates to whom a single dose of 50 mg/kg had been administered intramuscularly or intravenously. After intramuscular injection, concentrations of ceftazidime in serum were comparable to those obtained with the intravenous dose, although they were more variable. Peak serum levels ranging from 50 to 102 micrograms/ml were reached 30 to 60 min after intramuscular injection. The concentrations declined monoexponentially after the peak, with a mean half-life of 3.8 +/- 1.1 h. Concentrations of ceftazidime in serum declined biexponentially after intravenous injection, with a terminal half-life of 4.7 +/- 1.5 h.
PMCID: PMC185416  PMID: 6362562
5.  Comparative activities of norfloxacin and fifteen other antipseudomonal agents against gentamicin-susceptible and -resistant Pseudomonas aeruginosa strains. 
We compared the activity of norfloxacin (MK-0366), a new orally absorbable derivative of naladixic acid, with those of other antipseudomonal agents against Pseudomonas aeruginosa. Norfloxacin was the most active against both gentamicin-susceptible and gentamicin-resistant strains, having 90% minimal inhibitory concentrations of 2 and 8 micrograms/ml, respectively. This excellent in vitro activity may make norfloxacin effective for oral therapy of P. aeruginosa urinary tract infections.
PMCID: PMC185382  PMID: 6228193
6.  Lack of efficacy of AMP against recrudescent genital herpes infections in guinea pigs. 
AMP was evaluated for its efficacy against herpes simplex virus type 2 genital infections in guinea pigs. Vaginally infected animals were treated twice a day with AMP at 50 mg/kg per dose for 2 weeks. Subcutaneous doses were started 10 weeks postinfection. AMP treatment did not reduce the number of animals with recrudescent episodes when compared with saline-treated controls. In addition, AMP treatment did not reduce either the number of lesions or the duration of the recrudescent episodes which did develop. These results suggest that AMP has no effect on recrudescent herpes simplex virus type 2 vaginal infections.
PMCID: PMC185385  PMID: 6685993
7.  Intermittent chemoprophylaxis for Pneumocystis carinii pneumonia. 
An intermittent regimen of trimethoprim-sulfamethoxazole was tested in the corticosteroid-treated rat model to learn whether or not administration for 3 consecutive days a week would provide prophylaxis equal to continuous daily doses. Although all of the untreated control animals acquired Pneumocystis carinii pneumonia, none of the animals given either continuous or intermittent trimethoprim-sulfamethoxazole became infected.
PMCID: PMC185158  PMID: 6605717
8.  Pharmacokinetics and tissue penetration of ticarcillin combined with clavulanic acid. 
A combination of 3 g of ticarcillin and 200 mg of clavulanic acid was administered intravenously to six healthy male volunteers, after which the concentrations of these agents in serum and blister fluid were measured. The ratio of the two drugs in serum varied from 15:1 (ticarcillin-clavulanic acid) at the time of administration to 28:1 at 30 min and 62:1 at 5 h after injection. Both agents penetrated blister fluid rapidly, the ratio being 33:1 at 1 h and 66:1 at 3 h. The elimination rates of these agents were different, but for each compound they were similar in serum and blister fluid.
PMCID: PMC184977  PMID: 6614890
9.  Comparative in vitro activity of Sch 29,482, a new oral penem, against Neisseria gonorrhoeae. 
The in vitro activity of Sch 29,482, a new oral beta-lactam antimicrobial agent, was compared with those of norfloxacin, rosoxacin, ampicillin, erythromycin, and tetracycline against 142 Neisseria gonorrhoeae strains. Sch 29,482 was as active as norfloxacin and rosoxacin. Its activity was greater than the other three antimicrobial agents. It inhibited 90% of the isolates, regardless of beta-lactamase activity, at a concentration of less than or equal to 0.06 micrograms/ml.
PMCID: PMC184673  PMID: 6405687
10.  Comparative Concentrations of Cefoxitin in Human Lungs and Sera 
Eleven patients about to undergo pulmonary surgery received a bolus injection of 1 g of cefoxitin. The concentrations of cefoxitin in the serum 1 and 2 h after dosage were 38.5 ± 1.89 and 23.7 ± 2.56 μg/ml; the lung concentrations at the respective times were 12.6 ± 0.7 and 10.06 ± 0.43 μg/ml.
PMCID: PMC186046  PMID: 6838190
11.  Mechanism of action of habekacin, a novel amino acid-containing aminoglycoside antibiotic. 
The molecular basis for activity of habekacin was studied by using Escherichia coli Q-13. Electron microscopic studies revealed that numerous blebs, derived from the outer membrane, were formed on cells treated with habekacin. Cytoplasmic contents leaked into the lumina of blebs, and the membrane of some enlarged blebs was disrupted. In a cell-free system, habekacin interfered with polypeptide synthesis, caused codon misreading, and inhibited translocation of N-acetylphenylalanyl-tRNA from the acceptor site to the donor site on ribosomes. [3H]habekacin bound to both 50S and 30S ribosomal subunits. The current experiments indicated that the mechanism of action of habekacin is similar to that of 2-deoxystreptamine-containing aminoglycoside antibiotics such as dibekacin, kanamycin, gentamicin, and related substances. The relationship of membrane damage to inhibition of ribosomal functions remains to be determined.
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PMCID: PMC185944  PMID: 6362557
12.  Effect of azlocillin on uric acid levels in serum. 
Uric acid levels in serum were observed to fall precipitously in a group of 20 hospitalized asthmatic patients receiving azlocillin, bronchodilators, and steroids. None of the 20 hospitalized controls receiving the antiasthma therapy without azlocillin showed any decline in their uric acid levels. The levels for the azlocillin-treated group fell from a mean of 6.4 mg/dl to mean of 2.3 mg/dl, whereas those for the control group initially were 7.0 mg/dl and fell only to a mean of 6.5 mg/dl.
PMCID: PMC185384  PMID: 6651284
13.  Susceptibility of Mycobacterium tuberculosis to pyrazinamide and its relationship to pyrazinamidase activity. 
Pyrazinamidase activity has been associated with pyrazinamide-susceptible Mycobacterium tuberculosis strains. The detection of pyrazinamidase activity by the Wayne method was found to be of limited value when compared with the results of standard pyrazinamide susceptibility tests, especially when a high level of pyrazinamide resistance was found. When resistance to pyrazinamide reached a level of 150 to 200 micrograms/ml, there was too much variability in Wayne test results to accurately define pyrazinamide susceptibility.
PMCID: PMC185381  PMID: 6418066
14.  Comparison of ketoconazole, Bay N7133, and Bay L9139 in the treatment of experimental vaginal candidiasis. 
The efficacies of ketoconazole and two new imidazole preparations, Bay N7133 and Bay L9139, were compared in a rat model of experimental candida vaginitis. With a dosage regimen of 10 mg/kg by gavage for 5 days, the cure rate for ketoconazole was 96% as compared with rates of 23 and 29% for Bay N7133 and Bay L9139, respectively (P less than 0.001). Follow-up vaginal cultures at 30 days revealed a relapse in only 1 of 27 rats treated with ketoconazole. Our subsequent experiment in which ketoconazole regimens of 10 mg/kg were compared with Bay N7133 and Bay L9139 regimens of 25 mg/kg demonstrated cure rates of 100, 15, and 82% for the respective agents.
PMCID: PMC185340  PMID: 6314893
15.  Resistance of gram-negative bacilli as related to hospital use of antimicrobial agents. 
The development of resistance of gram-negative bacilli, which are common nosocomial pathogens, is an increasing problem. It is generally accepted that this resistance may directly reflect the frequency of use of various antimicrobial agents. Because our institution experienced in 1976 a dramatic change in the pattern of antimicrobial use, primarily a marked decrease in prescribing cephalosporins, we attempted to evaluate retrospectively the effects of this change upon the resistance of gram-negative bacilli that are common nosocomial pathogens. Susceptibilities of Klebsiella and Providencia spp., Pseudomonas aeruginosa, and Serratia marcescens were determined for the years 1975 to 1979. Not unexpectedly, we observed a substantial decrease in cephalosporin resistance. An unexpected finding was a decrease in aminoglycoside resistance, despite increased use of these agents. The possibility that decreased cephalosporin use may lead to decreased aminoglycoside resistance is an intriguing and provocative thesis which can only be speculative at this time but which would seem worthy of additional formal investigation.
PMCID: PMC185324  PMID: 6638994
16.  Minimal inhibitory concentrations of lucknomycin, a new polyenic derivative, for Candida and Aspergillus spp. 
The minimal inhibitory concentrations (MICs) of lucknomycin, a new polyenic derivative, were determined for 101 clinical isolates of Candida, 38 clinical or environmental strains of Aspergillus fumigatus, and 30 isolates of A. niger. The most susceptible species were Candida albicans and Candida tropicalis (mean MIC, 0.4 micrograms/ml). Aspergillus spp. were less susceptible, with mean MICs of 0.60 micrograms/ml for Aspergillus niger and 9.2 micrograms/ml for Aspergillus fumigatus.
PMCID: PMC185117  PMID: 6625552
17.  Occurrence and expression of imipemide (N-formimidoyl thienamycin) resistance in clinical isolates of coagulase-negative staphylococci. 
More than 500 clinical isolates were screened for resistance to a number of antibiotics, including imipemide (N-formimidoyl thienamycin [MK0787]). Of the 25 coagulase-negative staphylococcal isolates present in the screening sample, almost one-third showed one of two patterns of imipemide resistance. One pattern apparently involves constitutive expression of drug resistance, whereas the other pattern seems to result from an inducible resistance having an apparent induction threshold higher than the minimal inhibitory concentration of imipemide. The mechanism(s) responsible for this imipemide resistance is unclear, but may be distinct from the more common staphylococcal mechanisms of resistance to beta-lactam antibiotics. Only two of the patients from whom imipemide-resistant staphylococci were cultured had actually been treated with the antibiotic.
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PMCID: PMC185105  PMID: 6578701
18.  Comparison of cephalothin and ceforanide prophylaxis in cardiac surgery with cardiopulmonary bypass. 
Eighty-five patients undergoing cardiac surgery with cardiopulmonary bypass were given either cephalothin or ceforanide perioperatively in randomized, blinded fashion. The incidence of surgically related, postoperative infections was 23% for the cephalothin- and 26% for the ceforanide-treated groups. There were no statistically significant differences that could be identified between patients who became infected and those who remained free of infections, although the time spent in the operating theater was longer for the former group. Ceforanide achieves adequate levels in plasma and myocardial tissue that are sustained several hours after a 0.5-g parenteral dose and allows a 12-h interval between doses. Other currently available agents would have to be administered more frequently to achieve similar results.
PMCID: PMC185108  PMID: 6354078
19.  Clinical trial of cefonicid for treatment of skin infections. 
Twenty patients with skin and soft-tissue infections were treated with parenteral cefonicid. Cultures obtained in cellulitis cases from an aspirate of a leading edge of inflammation were positive in 42% of these patients. Pathogens isolated were Staphylococcus aureus (six strains), Proteus mirabilis (one strain), and Streptococcus agalactiae. Adverse effects were pain on intramuscular injection (two patients), rash (one patient), and positive Coombs test (one patient). All side effects were mild and none required discontinuing antibiotic therapy. A single treatment failure occurred in a patient with an undrained perirectal abscess. Cefonicid may be a useful drug in the treatment of skin and soft-tissue infections. The long half-life of cefonicid (4.8 h) is a valuable advantage and may facilitate patient compliance and convenience.
PMCID: PMC185015  PMID: 6351735
20.  In vitro antimicrobial activity of eight new beta-lactam antibiotics against penicillin-resistant Neisseria gonorrhoeae. 
Increasing numbers of cases of penicillin-resistant gonorrhea necessitate the evaluation of new antibiotics for treatment of this disease. We tested the susceptibility of 92 penicillinase-producing (PP) Neisseria gonorrhoeae isolates and 88 penicillin-susceptible (PS) isolates to eight new beta-lactam antibiotics. The minimal inhibitory concentrations of these antibiotics were determined by the agar plate method. PP and PS N. gonorrhoeae isolates were susceptible to clinically achievable levels of all antibiotics tested. There were, however, marked differences among the drugs with regard to the concentration required to inhibit growth. The PP N. gonorrhoeae isolates were extremely susceptible to ceftriaxone, ceftizoxime, and cefotaxime, highly susceptible to moxalactam and cefoperazone, and less susceptible to cefoxitin, ceforanide, and cefonicid (geometric mean minimal inhibitory concentrations were 0.002, 0.003, 0.007, 0.03, 0.07, 0.6, 2.4, and 3.1 micrograms/ml, respectively). Although this in vitro study showed PP N. gonorrhoeae isolates to be comparatively more susceptible to ceftriaxone, ceftizoxime, and cefotaxime than to the other antibiotics, these results may not correlate with clinical efficacy.
PMCID: PMC184696  PMID: 6407392
21.  Delayed bactericidal activity of beta-lactam antibiotics against Listeria monocytogenes: antagonism of chloramphenicol and rifampin. 
Penicillins are considered to be the drugs of choice for the treatment of listeric meningitis, and relapse of infection is rare when treatment is given in appropriate doses for at least 14 days. Despite this, in vitro studies by others have shown that penicillins are bacteriostatic against Listeria spp. We have shown that thienamycin, penicillin G, and ampicillin are the most active beta-lactam antibiotics against Listeria spp. Of 10 strains tested, 9 were killed by less than or equal to 8 micrograms of beta-lactam antibiotics (greater than or equal to 99.9% killing) when subcultures were performed after 48, rather than 24, h of incubation. In contrast, chloramphenicol, erythromycin, doxycycline, and rifampin were bacteriostatic after 48 h of incubation. In time-kill curves, these last drugs antagonized the bactericidal action of penicillins. In view of the inefficiency of opsonization in the cerebrospinal fluid, these antagonistic combinations should probably be avoided in documented or suspected listeric meningitis.
PMCID: PMC184700  PMID: 6407393
22.  In vitro activity of a group of broad-spectrum cephalosporins and other beta-lactam antibiotics against Chlamydia trachomatis. 
The activities of seven broad spectrum cephalosporins, four other beta-lactam antibiotics, and one monobactam against Chlamydia trachomatis were measured in a cell culture system. The minimal inhibitory concentration of four of the seven cephalosporins was greater than or equal to 128 micrograms/ml; those of the other three were from 16 to 32 micrograms/ml. Of the other agents, only mecillinam had activity against C. trachomatis comparable to that reported for ampicillin (minimal inhibitory concentration, less than or equal to 0.5 micrograms/ml).
PMCID: PMC184677  PMID: 6847175
23.  Antimicrobial susceptibilities of bacteria associated with periodontal disease. 
A total of 193 bacterial strains were tested for their susceptibilities to 14 antimicrobial agents. Penicillin G was active at 2 U/ml against 98% of the oral isolates. Other antibiotics with good activity were cefoperazone, moxalactam, Sch 29,482, and clindamycin. Metronidazole was active against more than 90% of the anaerobic bacteria and Capnocytophaga but was inactive against most other microaerophilic and facultative strains.
PMCID: PMC184674  PMID: 6601929
24.  Scarring as a factor affecting the eradication of microorganisms from the kidney in pyelonephritis. 
The inability of antimicrobial agents to penetrate scarred renal tissue may explain some therapeutic failures. We examined the effect of scarring on antimicrobial therapy by using a unique animal model in which both kidneys were infected to the same degree but only one kidney was scarred. Scar formation could not explain the failure of ampicillin or nitrofurantoin to eradicate renal infection, but co-trimoxazole was less effective in the presence of tissue damage and scar formation than in their absence.
PMCID: PMC184680  PMID: 6601931
25.  Comparative in vitro activity of cefodizime, ceftazidime, aztreonam, and other selected antimicrobial agents against Neisseria gonorrhoeae. 
The in vitro activities of three new beta-lactam antimicrobial agents, cefodizime, ceftazidime, and aztreonam (formerly azthreonam), were compared with those of cefotaxime, cefuroxime, cefoxitin, and penicillin against 100 beta-lactamase-negative and 42 beta-lactamase-positive Neisseria gonorrhoeae strains. The three new antimicrobial agents showed excellent activity against N. gonorrhoeae regardless of beta-lactamase production. Cefodizime was as active as cefotaxime and more active than the other test antimicrobial agents. It inhibited all isolates at a concentration of less than or equal to 0.016 micrograms/ml.
PMCID: PMC184671  PMID: 6303215

Results 1-25 (393)