Showing papers in "Antimicrobial Agents and Chemotherapy in 1974"
TL;DR: The efficacy of silver sulfadiazine is thought to result from its slow and steady reactions with serum and other sodium chloride-containing body fluids, which permits the slow and sustained delivery of silver ions into the wound environs.
Abstract: The role of silver and sulfadiazine in the mechanism of action of silver sulfadiazine on burn wound infections was investigated. Silver, but not sulfadiazine, was bound by bacteria. Sulfadiazine did not act as an antibacterial agent in low concentrations, but exhibited specific synergism in combination with subinhibitory levels of silver sulfadiazine. The efficacy of silver sulfadiazine is thought to result from its slow and steady reactions with serum and other sodium chloride-containing body fluids, which permits the slow and sustained delivery of silver ions into the wound environs. In this circumstance, a relatively minute amount of sulfadiazine appears active.
304 citations
TL;DR: Probenecid may prove useful in certain bacterial infections where high CSF antibiotic levels are necessary, and was consistently demonstrated in animals with experimental pneumococcal meningitis.
Abstract: Probenecid may elevate the cerebrospinal fluid (CSF) concentration of penicillin G by inhibiting the excretion of organic acids from CSF. We have studied this phenomenon with various penicillin and cephalosporin derivatives. Penicillin concentrations were determined in rabbits under steady-state conditions before and after intravenous probenecid administration. With both low-dose and high-dose probenecid, CSF penicillin levels increased two to three times as did CSF concentration as a percentage of serum level. The same probenecid effect was consistently demonstrated in animals with experimental pneumococcal meningitis. Probenecid likewise increased the CSF concentration of ampicillin, carbenicillin, nafcillin, cephacatrile, and cefazolin. Probenecid may prove useful in certain bacterial infections where high CSF antibiotic levels are necessary.
279 citations
TL;DR: Electrochemically injected silver from the anode is probably the instrumental agent, being effective in concentrations of about 5 μg/ml, which is the equivalent concentration of silver sulfadiazine that has been shown to give complete inhibition of bacteria, but without the sulfonamide moiety.
Abstract: Silver, platinum, gold, stainless-steel, and copper electrodes were used with low currents (0.02 to 20 μA/mm 2 ) to explore their electrochemical effects on the growth of four bacterial species. In the higher current ranges, all electrodes inhibited growth at both poles, usually in conjunction with electrolytic break-down of the medium and severe corrosion of the metal. Silver, however, was extremely bacteriostatic, even at the lowest current, when used as the anode. Quantitative studies showed that most of this inhibition takes place in a few hours and is not accompanied by changes in pH. Electrochemically injected silver from the anode is probably the instrumental agent, being effective in concentrations of about 5 μg/ml. This is the equivalent concentration of silver sulfadiazine that has been shown to give complete inhibition of bacteria, but without the sulfonamide moiety. Images
255 citations
TL;DR: A combination of trimethoprim and sulfamethoxazole was effective in the prevention and treatment of Pneumocystis carinii pneumonitis in cortisonetreated rats, and rifampin and clindamycin, separately or in combination with pentamidine, were ineffective.
Abstract: A combination of trimethoprim and sulfamethoxazole was effective in the prevention and treatment of Pneumocystis carinii pneumonitis in cortisonetreated rats. Although all of 15 untreated rats died with P. carinii pneumonitis, none of 15 given trimethoprim-sulfamethoxazole prophylactically acquired the infection. After P. carinii pneumonitis was established, 9 of 14 rats recovered after treatment with trimethoprim-sulfamethoxazole compared with only 2 of 14 treated with pentamidine isethionate. Rifampin and clindamycin, separately or in combination with pentamidine, were ineffective in the prevention and treatment of P. carinii infection.
205 citations
TL;DR: Mutanolysin partially purified from the culture filtrate of Streptomyces globisporus 1829 consists of two main lytic enzymes with an isoelectric point near pH 8.5 and 10, respectively, and proteolytic enzyme is associated with the latter lytic enzyme.
Abstract: Mutanolysin partially purified from the culture filtrate of Streptomyces globisporus 1829 consists of two main lytic enzymes with an isoelectric point near pH 8.5 and 10, respectively, and proteolytic enzyme is associated with the latter lytic enzyme. Mutanolysin exhibited maximal lytic activity at 60 C in the pH range 6.5 to 7.0 and was stable at 50 C in the acid range. N-bromosuccinimide caused complete inhibition of lytic activity at 1 mM, whereas calcium and magnesium ions at the same concentration caused activation. Mutanolysin had lytic or bactericidal activity against the living cells of Streptococcus mutans, Streptococcus salivarius, Streptococcus sanguis, Lactobacillus acidophilus, and Actinomyces viscosus, which are considered to be etiologic agents of dental caries, but had no activity against S. aureus and all gram-negative strains tested. The lytic activity was well retained in human saliva. Digestion of the cell walls of S. mutans BHT by mutanolysin was accompanied by the liberation of free amino groups and reducing sugars. Mutanolysin may be expected to be a useful agent for dental caries control.
151 citations
TL;DR: Replication of herpes simplex virus in WI-38 cells was inhibited by phosphonoacetic acid, as measured by decreased virus cytopathogenic effect and incorporation of radiolabeled thymidine in virus-infected cells.
Abstract: Replication of herpes simplex virus in WI-38 cells was inhibited by phosphonoacetic acid, as measured by decreased virus cytopathogenic effect and incorporation of radiolabeled thymidine in virus-infected cells. The drug appeared to have no effect on adsorption, penetration, or release of the virus nor on the synthesis of ribonucleic acid or protein. It appeared to inhibit virus deoxyribonucleic acid synthesis. Images
145 citations
TL;DR: The limulus gelation assay was utilized to investigate endotoxin inactivation by a number of antibiotics in vitro, and a 10,000-fold range in the relative susceptibility of different endotoxins to in activation by polymyxin B was found.
Abstract: The limulus gelation assay was utilized to investigate endotoxin inactivation by a number of antibiotics in vitro. Endotoxin activity was sharply reduced by polymyxin B and sodium colistimethate. The effect of the polymyxin was not significantly inhibited by 0.001 M calcium or 90% serum. Crude endotoxins from a variety of aerobic gram-negative bacteria, including several not previously studied, could be inactivated 1 or more logs by as little as 1 μg of polymyxin B per ml, whereas Bacteroides fragilis endotoxin was poorly detoxified. A 10,000-fold range in the relative susceptibility of different endotoxins to inactivation by polymyxin B was found. The endotoxin most susceptible to polymyxin B was derived from an organism resistant to polymyxin B by disk sensitivity testing, suggesting that the bacteriocidal and endotoxin detoxifying properties of polymyxin need not be directly related.
139 citations
TL;DR: A rapid capillary tube method was used to demonstrate beta-lactamase production by ampicillin-resistant strains of Haemophilus influenzae.
Abstract: A rapid capillary tube method was used to demonstrate beta-lactamase production by ampicillin-resistant strains of Haemophilus influenzae.
139 citations
TL;DR: Inoculum size and type of medium had variable effects on the minimal inhibitory concentration, depending upon the particular strain tested, and strains of Enterobacter, Serratia, indole-positive Proteus species showed the greatest inoculum effect.
Abstract: The in vitro activity of cefamandole, 7-d-mandelamido-3-(1 methyl-1H-tetrazol-5 yethiomethyl)-3-cephem-4 carboxylic acid, was investigated. The majority of streptococci and pneumococci were inhibited by 0.1 mug/ml. Activity against Staphylococcus aureus was below that of cephalothin, but most strains were inhibited by 0.4 mug/ml. Enterococci were not inhibited by less than 25 mug/ml. Cefamandole was very active against most members of the Enterobacteriaceae, with 70% of Escherichia coli, 86% of Klebsiella pneumoniae, and 88% of Proteus mirabilis inhibited by 1.6 mug/ml. A number of Enterobacter aerogenes, Proteus vulgaris, and Serratia marcescens strains were inhibited by less than 25 mug/ml. Pseudomonas species were resistant. Cefamandole was more active than cephalothin, cephaloridine, or cephalexin against members of the Enterobacteriaceae. Inoculum size and type of medium had variable effects on the minimal inhibitory concentration, depending upon the particular strain tested. Strains of Enterobacter, Serratia, indole-positive Proteus species showed the greatest inoculum effect. Similarly, these species showed a several-fold difference of bactericidal and inhibitory levels. Resistance of cefamandole to hydrolysis by gram-negative beta-lactamase played a partial role in its activity, but some strains that hydrolyzed the agent were susceptible.
137 citations
TL;DR: The role of the constitutive and inducible enzyme in bacterial resistance to the antibiotic was investigated and enzymatic destruction of cefoxitin was found to be an important factor contributing to bacterial resistance.
Abstract: Cefoxitin is a new, cephalosporin-like antibiotic which is highly resistant to hydrolysis by beta-lactamase. Ninety-one cultures were selected either for their general resistance to cephalosporin antibiotics or for their ability to produce beta-lactamase. Some of these cultures were resistant to cefoxitin. The capacity of each of the 91 strains to hydrolyze cefoxitin with beta-lactamase was determined. Only seven of the cultures degraded the antibiotic as determined by a general assay for beta-lactamase. Several others were able to hydrolyze cefoxitin after enzyme was induced by low concentrations of the antibiotic. The role of the constitutive and inducible enzyme in bacterial resistance to the antibiotic was investigated. Enzymatic destruction of cefoxitin was found to be an important factor contributing to bacterial resistance. However, the complete and rapid degradation of cefoxitin is not essential to resistance since one strain, Enterobacter cloacae 1316, hydrolyzed the antibiotic very slowly but was able to grow unaffected in the presence of cefoxitin. The presence of the enzyme is not necessarily sufficient to confer resistance since another culture, Klebsiella D535, readily hydrolyzed the antibiotic but was susceptible to it.
136 citations
TL;DR: It is shown that the antifungal drug alters the cellular permeability, and thus the exogenous respiration becomes sensitive to the drug.
Abstract: The antifungal drug, miconazole nitrate, inhibits the growth of several species of Candida. Candida albicans, one of the pathogenic species, was totally inhibited at a concentration of approximately 10 μg/ml. Endogenous respiration was unaffected by the drug at a concentration as high as 100 μg/ml, whereas exogenous respiration was markedly sensitive and inhibited to an extent of 85%. The permeability of the cell membrane was changed as evidenced by the leakage of 260-nm absorbing materials, amino acids, proteins, and inorganic cations. The results we present clearly show that the drug alters the cellular permeability, and thus the exogenous respiration becomes sensitive to the drug.
TL;DR: Two clinical isolates of Pseudomonas aeruginosa could transfer gentamicin resistance by conjugation, and four plasmids in this incompatibility group determine additional biological properties, including resistance to inorganic and organic mercury compounds, to ultraviolet light, and to certain deoxyribonucleic acid phages.
Abstract: Two clinical isolates of Pseudomonas aeruginosa, one a pyocin type 5 strain from Atlanta, could transfer gentamicin resistance by conjugation. Donor and recipient strains inactivated gentamicin by acetylation. The R plasmids, pMG1 and pMG2, also determined resistance to sisomicin, another substrate of gentamicin acetyltransferase I, sulfonamides, and streptomycin, but not resistance to kanamycin, neomycin, tobramycin, butirosin, or BB-K 8. They were transmissible to many strains of P. aeruginosa, including a Rec(-) strain, but not to Escherichia coli or other enterobacteriaceae. These R plasmids were compatible with R plasmids transmissible to P. aeruginosa from E. coli, including members of C, N, P, and W incompatibility groups. From a strain carrying pMG1 and a compatible plasmid, pMG1 was transferred independently but transfer of the second plasmid often resulted in cotransfer of pMG1. In contrast, pMG1 and pMG2 were incompatible with pseudomonas R plasmids R931 and R3108, and with R931 they readily formed recombinant plasmids. The four plasmids in this incompatibility group determine additional biological properties, including resistance to inorganic and organic mercury compounds, to ultraviolet light, and to certain deoxyribonucleic acid phages. pMG1 and pMG2 also phenotypically inhibited pyocin production. Consequently such R plasmids alter the phage and pyocin types of their host strains.
TL;DR: Selected clinical isolates of Haemophilus influenzae were tested for their susceptibility to seven antibiotics by a microtiter broth dilution and an agar diffusion method, and eleven of 40 strains tested were resistant to ampicillin, the drug of choice, by both methods.
Abstract: Selected clinical isolates of Haemophilus influenzae were tested for their susceptibility to seven antibiotics by a microtiter broth dilution and an agar diffusion method. Eleven of 40 strains tested were resistant to ampicillin, the drug of choice, by both methods. All the strains tested were susceptible to chloramphenicol, and all but one were susceptible to tetracycline. Of the other four antibiotics tested, the ranges of minimal inhibitory concentrations (MICs) were: 0.5 to 4 μg of gentamicin per ml, 0.5 to 4 μg of erythromycin per ml, and 2 to 16 μg of clindamycin per ml. MICs of ampicillin for both the susceptible and resistant strains were markedly affected by inoculum concentration. The ampicillin MICs of the resistant strains were also affected by the time of incubation.
TL;DR: The broad spectrum of amikacin was not totally unexpected, because the compound has been shown to be a poor substrate for most enzymes that inactivate other aminoglycosides through O-phosphorylation, O-adenylylation, or N-acetylation.
Abstract: One hundred fifty-two bacterial strains that possess resistance to kanamycin A, gentamicin, or tobramycin, or to more than one of these antibiotics, were collected from various sources in Canada, Europe, Japan, and the United States. This collection was composed of Staphylococcus aureus and Pseudomonas aeruginosa and members of the Enterobacteriaceae family. Their susceptibility to BB-K8 (amikacin), a new broad-spectrum semisynthetic derivative of kanamycin A, and to the other agents, was determined on Mueller-Hinton Medium by the twofold agar dilution method. Test results revealed that 60.5% of the isolates were resistant to 8 mug of tobramycin per ml, 67.1% to 8 mug of gentamicin per ml, 86.2% to 20 mug of kanamycin A per ml, and only 8.6% to 20 mug of amikacin per ml. Of interest is the fact that the amikacin-resistant strains were generally resistant to all of the other aminoglycosides. The broad spectrum of amikacin was not totally unexpected, because the compound has been shown to be a poor substrate for most enzymes that inactivate other aminoglycosides through O-phosphorylation, O-adenylylation, or N-acetylation. A number of susceptibility profiles were obtained when the organisms were tested against a series of nine aminoglycosides. The majority of these profiles resembled those found for organisms that possess known mechanisms of enzymatic inactivation.
TL;DR: Cefoxitin, 3-carbamoyloxymethyl-7-α-methoxy-7-[2-thienyl)acetamido]-3-cephem-4- carboxylic acid, is a new semisynthetic cephamycin with broad antibacterial activity.
Abstract: Cefoxitin, 3-carbamoyloxymethyl-7-α-methoxy-7-[2-(2-thienyl)acetamido]-3-cephem-4- carboxylic acid, is a new semisynthetic cephamycin with broad antibacterial activity. It is highly active against gram-negative microorganisms including indole-positive Proteus and Serratia strains, which are ordinarily reistant to the cephalosporins. Cefoxitin is also highly active against many strains of Escherichia coli and Proteus mirabilis which are resistant to the cephalosporins. Furthermore, E. coli and Klebsiella strains which are susceptible to the cephalosporins are generally more susceptible to the cephamycin analog. The susceptibility of the gram-positive bacteria falls well within the effective range of the antibiotic for gram-negative organisms, but cefoxitin is less active than cephalothin or cephaloridine. As is the case with the cephalosporins, strains of Pseudomonas and group D streptococci are resistant to cefoxitin. Changes in pH, inoculum density, and growth medium have no significant effect on the activity of the antibiotic.
TL;DR: It is concluded that the formation of a complex between vancomycin and a postulated cell wall acceptor or betweenVancomyc and the enzymes involved in peptidoglycan synthesis does not contribute to the inhibitory action of this antibiotic.
Abstract: Vancomycin inhibits the synthesis of peptidoglycan in membrane preparations from Gaffkya homari with uridine diphosphate- N -acetylmuramyl (UDP-Mur-NAc)-pentapeptide as substrate, but not with either UDP-MurNAc-tetrapeptide or UDP-MurNAc-tripeptide. These results are correlated with the specificity studies described by Perkins and Nieto for complex formation between the antibiotic and the peptide subunit. It is concluded that the formation of a complex between vancomycin and a postulated cell wall acceptor or between vancomycin and the enzymes involved in peptidoglycan synthesis does not contribute to the inhibitory action of this antibiotic. The mechanism of vancomycin action on peptidoglycan synthesis is clearly different from that of moenomycin and bacitracin. In the presence of these antibiotics, peptidoglycan synthesis is inhibited with both UDP-MurNAc-pentapeptide and -tetrapeptide as substrates. In addition, these results provide additional insight into the mechanism of phospho-MurNAc-pentapeptide translocase. For example, enhancement of the transfer of phospho-MurNAc-peptide from UDP-MurNAc-peptide to undecaprenyl-phosphate at low concentrations of vancomycin is observed with UDP-MurNAc-pentapeptide and not with -tetrapeptide. Complexation of vancomycin with undecaprenyl-diphosphate-MurNAc-pentapeptide, resulting in an ineffective intermediate, would increase the rate of transfer by preventing the reassociation of undecaprenyl-diphosphate-MurNAc-pentapeptide with the enzyme.
TL;DR: Blood levels increased progressively for the first few doses and then leveled off, with no significant accumulation occurring between 3 and 7 days, and since the minimum inhibitory concentrations of most anaerobes including Bacteroides fragilis are less than 6 μg/ml, these concentrations should be highly effective therapeutically, even for severe infections.
Abstract: The pharmacokinetics of metronidazole, a drug effective in vitro against most anaerobic bacteria and promising in treating anaerobic infections, are described. Serum and urine levels after single and multiple doses in 10 adult male volunteers were measured by an agar well diffusion bioassay using clostridial species as the test organisms under anaerobic conditions. Peak serum levels averaged 11.5 mug/ml and 6.2 mug/ml after single 500-mg and 250-mg doses, respectively. Renal clearance was only 10.2 ml/min per 1.73 m(2), and less than 20% of the administered dose was recovered in the urine as active drug in 24 h. The average serum half-life was 8.7 h, and there was no protein binding as determined by an ultrafiltration method. With multiple doses of metronidazole (500 mg four times a day and 250 mg three times a day), blood levels increased progressively for the first few doses and then leveled off, with no significant accumulation occurring between 3 and 7 days. On 250 mg three times a day, serum levels just before the 8 a.m. dose (12 h after the preceding dose) on the third day averaged 3.9 mug/ml, and before the 8 p.m. dose, 5.7 mug/ml. For the higher, 500-mg dose (four times a day) regimen, the corresponding minimum serum levels were 13.1 mug/ml at 8 a.m. and 21.3 mug/ml at 8 p.m. Peak levels would have been about 10 mug/ml higher, and since the minimum inhibitory concentrations of most anaerobes including Bacteroides fragilis are less than 6 mug/ml, these concentrations should be highly effective therapeutically, even for severe infections.
TL;DR: Fusarium equiseti NRRL 5537 grown on an autoclaved white corn grit medium for 3 to 4 weeks at room temperature produced a substance in excess of 5 g/kg of substrate that inhibited some gram-positive bacteria including mycobacteria, which inhibited most Bacillus subtilis, Mycobacterium phlei, and Staphylococcus aureus strains.
Abstract: Fusarium equiseti NRRL 5537 grown on an autoclaved white corn grit medium for 3 to 4 weeks at room temperature produced a substance in excess of 5 g/kg of substrate that inhibited some gram-positive bacteria including mycobacteria. Most Bacillus subtilis, Mycobacterium phlei, and Staphylococcus aureus strains were inhibited when 1 mug of the antibiotic per ml was incorporated into the culture medium. Except for Neisseria perflava, gram-negative bacteria, yeasts, and molds were not inhibited by 128 mug/ml. The antibiotic was recovered as a white powder, had a melting point of 65 to 66 C, and had an intraperitoneal mean lethal dose in white mice of 63 mg/kg of body weight. In thin-layer chromatographic analysis the compound appeared as a single spot in two different solvent systems. Mass spectrometry determined that the molecular weight of the antibiotic was 373 with a molecular formula of C(22)H(31)NO(4). Chemical microanalysis was in accord with the formula.
TL;DR: A plasmid determining resistance to erythromycin, lincomycin, and vernamycin Bα was isolated from a strain of Streptococcus pyogenes.
Abstract: A plasmid determining resistance to erythromycin, lincomycin, and vernamycin B α was isolated from a strain of Streptococcus pyogenes . The plasmid has a molecular weight of approximately 17 × 10 6 and is present to the extent of one to two copies per chromosomal genome equivalent. Images
TL;DR: The drug effectively prevented death due to the acute infection and eradicated the organism at least from the liver, spleen, and brain of approximately 30 to 50% of the acutely infected animals which survived.
Abstract: The effect of clindamycin on survival of mice during acute infection with the RH and C56 strains of Toxoplasma and the ability of this drug to prevent congenital transmission during the acute stage of the infection in the mother and to eradicate the parasite from tissues of mice chronically infected with the C56 strain were evaluated. The drug effectively prevented death due to the acute infection and, in the experimental model employed, eradicated the organism at least from the liver, spleen, and brain of approximately 30 to 50% of the acutely infected animals which survived. Clindamycin also effectively prevented congenital transmission during the acute infection in the mother. During short-term treatment (7 days), persistent parasitemia in the chronic infection was effectively diminished or eradicated. More prolonged treatment resulted in a significant clearing of the organisms from the spleens and livers, but not from the brains, of chronically infected mice.
TL;DR: In vitro survey of 74 strains of actinomycetes, representing seven species, found no antimicrobial susceptibility differences among the species tested, and inhibition of gross colonial enlargement in semisolid antibiotic agar inhibited all strains of A. israelii.
Abstract: Current interest in antimicrobial susceptibility testing of anaerobic pathogens and recent recognition that actinomycetes other than Actinomyces israelii may cause actinomycosis in man prompted this in vitro survey of 74 strains of actinomycetes, representing seven species. Minimum inhibitory concentrations (MICs) for 24 antimicrobials were determined by inhibition of gross colonial enlargement in semisolid antibiotic agar after incubation at 37 C for 48 h under anaerobic conditions. Erythromycin and rifampin were the most active drugs in vitro (MICs of 0.008 to 0.25 μg/ml), although a small number of non-israelii strains were conspicuously more resistant to the latter (MICs >0.5 μg/ml). Penicillin G, cephaloridine, minocycline, and clindamycin were also very active in vitro (MICs of 0.03 to 1.0 μg/ml); for a few non-israelii strains the MICs of clindamycin were 2.0 to 8.0 μg/ml. MICs of cephalothin, ampicillin, lincomycin, tetracycline, doxycycline, and chloramphenicol were well within a therapeutic range for all strains of A. israelii and most other species, although the MIC of lincomycin against a few non-israelii strains and of tetracycline and doxycycline against the majority of these strains was 2.0 to 8.0 μg/ml. Oxacillin, dicloxacillin, and cephalexin were less active in vitro, particularly against strains other than A. israelii . Most non-israelii species were not suppressed by 125 μg of metronidazole per ml, which concentration inhibited all strains of A. israelii; otherwise, there were no antimicrobial susceptibility differences among the species tested. Aminoglycoside activity was negligible.
TL;DR: Antibiotic activity could be removed from pus by high concentrations of protamine sulfate, heparin, sodium chloride, or potassium chloride, suggesting binding rather than inactivation.
Abstract: To define factors contributing to the adverse prognosis of patients with gram-negative bacillemia and abscess formation, we studied the interaction between polymyxin B, colistin sulfate, gentamicin, or carbenicillin with purulent material Carbenicillin activity was not significantly altered by incubation with pus Equal volumes of antibiotic and purulent sediment decreased the effective concentration of polymyxin B, colistin sulfate, or gentamicin from 100 μg/ml to 3 to 6 μg/ml One milliliter of purulent sediment bound more than 700 μg of gentamicin and 1,500 μg of polymyxin B or colistin sulfate This effect occurred rapidly, proceeded at 4 and 37 C, was stable for 24 to 48 h, and was altered, but not abolished, by varying the pH of the solution Antibiotic activity could be removed from pus by high concentrations of protamine sulfate, heparin, sodium chloride, or potassium chloride, suggesting binding rather than inactivation
TL;DR: The in vitro activity of cefoxitin, 3-carbamolyloxymethyl-7-α-methoxy-7[2-(2-thienyl)acetamido]-3-cephem-4-carboyxlic acid, was investigated and it was highly active against gram-negative bacilli and resistance to beta-lactamase hydrolysis varied from strain to strain.
Abstract: The in vitro activity of cefoxitin, 3-carbamolyloxymethyl-7-alpha-methoxy-7[2-(2-thienyl)acetamido]-3-cephem-4-carboyxlic acid, was investigated. Activity against gram-positive organisms was less than that of cephalothin and cephloridine. It was highly active against gram-negative bacilli, with activity against Escherichia coli, Proteus mirabilis, and Klebsiella pneumoniae equal to that of currently available cephalosporins. In addition, it was active against certain Enterobacter strains, Serratia marcescens, indole-positive Proteae and Herellea. The strains of these latter bacteria were strains susceptible to carbenicillin and ticarcillin. Pseudomonas aeruginosa and other Pseudomonas species were resistant. Changes in pH, inoculum size, and type of growth medium had no significant effect on the activity of the antibiotic. Cefoxitin was highly resistant to hydrolysis by various types of gram-negative beta-lactamases. The precise role of resistance to beta-lactamase hydrolysis varied from strain to strain. Bacterial resistance to cefoxitin was not necessarily related to hydrolysis of the antibiotic. However, the resistance of cefoxitin to hydrolysis did contribute to its activity. Cefoxitin could function as an inducer of beta-lactamase activity and effectively bound to purified beta-lactamases.
TL;DR: By disk diffusion antimicrobial susceptibility testing, Pseudomonas aeruginosa recipients were much more effective for detection of transferable gentamicin resistance than Escherichia coli recipients, although not all P. aerugenosa were equally as effective as recipients.
Abstract: By disk diffusion antimicrobial susceptibility testing, 11% of 313 consecutive strains of Pseudomonas aeruginosa, examined during July to October 1973, were resistant to gentamicin (minimal inhibitory concentration 12.5 to >100 mug/ml), and a further 31% were moderately resistant (6.25 to 12.5 mug/ml) to gentamicin at the University of Alberta Hospital in Edmonton, Canada. Of 45 gentamicin-resistant strains from that hospital, none possessed R-factors or gentamicin-inactivating enzymes. Eight of 13 strains obtained from three American sources, which contained gentamicin-acetylating (12 strains) or -adenylating (1 strain) activity, conjugally transferred both gentamicin resistance and antibiotic-inactivating activity. P. aeruginosa recipients were much more effective for detection of transferable gentamicin resistance than Escherichia coli recipients, although not all P. aeruginosa were equally as effective as recipients. One strain, POW 151, transferred resistance to both carbenicillin and gentamicin as well as to several other antibiotics. R-factors detected belonged to P-2 and P-3 (Com 6, C) incompatibility groups. Expression of gentamicin resistance due to acetylation of gentamicin was subject to marked phenotypic lag, especially in recipient strain P. aeruginosa 280. This was shown to result in the failure to detect gentamicin resistance transfer if the concentration of gentamicin in selection media was too high (>2.5 mug/ml for strain 280). Some but not all recipients were changed in pyocine type upon acquisition of R-factors.
TL;DR: The effect of gentamicin against 130 clinical isolates of Pseudomonas aeruginosa was compared with that of two investigational aminoglycoside antibiotics, tobramycin and amikacin, and the combination of carbenicillin and amkacin enhanced inhibition against all but two of the isolates.
Abstract: The effect of gentamicin against 130 clinical isolates of Pseudomonas aeruginosa was compared with that of two investigational aminoglycoside antibiotics, tobramycin and amikacin. Minimal inhibitory concentration data indicated that, on a weight basis, tobramycin was two to four times as active as gentamicin against most isolates. However, 14 of 18 organisms highly resistant to gentamicin (>/=80 mug/ml) were also highly resistant to tobramycin. Amikacin was the least active aminoglycoside on a weight basis, but none of the isolates were highly resistant to this antibiotic. When therapeutically achievable concentrations were used, adding carbenicillin to gentamicin or to tobramycin enhanced inhibitory activity against those isolates susceptible (
TL;DR: All 17 Salmonella typhi strains tested from the epidemic in Mexico carried R factors of compatibility group H, conferring resistance to chloramphenicol, streptomycin, tetracycline, and sulfonamides, and all 20 Shigella dysenteriae 1 strains tested of epidemic origin carried O-group R factors.
Abstract: All 17 Salmonella typhi strains tested from the epidemic in Mexico carried R factors of compatibility group H, conferring resistance to chloramphenicol, streptomycin, tetracycline, and sulfonamides. Some S. typhi strains carried, in addition, non-conjugative, ampicillin resistance plasmids and R factors of the I or A–C complex. All 20 Shigella dysenteriae 1 strains tested of epidemic origin carried O-group R factors. Ampicillin resistance in S. dysenteriae 1 was not proved to be plasmid borne. R factors of group H were not identified in any of the tested Mexican isolates other than S. typhi, but R factors of group O were identified in Escherichia coli, Shigella flexneri, and one strain of S. typhi, as well as in the epidemic S. dysenteriae. An R factor was identified which seemed to have two compatibility specificities, groups Iω and O.
TL;DR: Preliminary results suggest that cephamycins may prove to be a significant chemotherapeutic advance.
Abstract: Cefoxitin, a semisynthetic cephamycin, has been compared with the widely used parenteral cephalosporin, cephalothin, in terms of antibacterial activity, human pharmacokinetics, and toxicity. For both compounds, minimal inhibitory concentrations were within the therapeutic range against the 156 gram-positive cocci tested (except group D streptococci), but cephalothin was 8 to 20 times more active. Regarding the 313 gram-negative organisms tested, both antibiotics were of approximately equal activity against cephalothin-susceptible strains, but cefoxitin was outstandingly superior against Providencia spp. and indole-producing Proteus spp., and markedly better against Serratia marcescens and Bacteroides fragilis. Against these organisms, cefoxitin but not cephalothin would be expected to be therapeutically valuable. Antibiotic activity levels in the serum and urine of 18 human volunteers after parenteral administration were higher and more prolonged in the case of cefoxitin, which had an average terminal serum half-life of about 45 min and a urinary recovery of about 90%. Cefoxitin was entirely nontoxic and, given intramuscularly, slightly less painful then cephalothin. These preliminary results suggest that cephamycins may prove to be a significant chemotherapeutic advance.
TL;DR: Among the polyene antibiotics, many, like filipin, cannot be used clinically because they are toxic; amphotericin B, however, is useful in therapy of human fungal infections because it is less toxic.
Abstract: Among the polyene antibiotics, many, like filipin, cannot be used clinically because they are toxic; amphotericin B, however, is useful in therapy of human fungal infections because it is less toxic. Both the toxicity of filipin and the therapeutic value of amphotericin B can be rationalized at the cellular and molecular level by the following observations: (i) these polyene antibiotics showed differential effects on cells; filipin was more potent in lysing human red blood cells, whereas amphotericin B was more potent in inhibiting yeast cell growth; and (ii) the effects of filipin were more efficiently inhibited by added cholesterol, the major membrane sterol in human cells, whereas the effects of amphotericin B were more efficiently inhibited by ergosterol, the major membrane sterol in yeast. The simplest inference is that the toxicity and effectiveness of polyenes are determined by their relative avidities for the predominant sterol in cell membranes.
TL;DR: Binding of erythromycin to ribosomes was rapid and reversible and the specific rate constants for the forward and reverse reactions were 1.7 × 107 liters per mol per min and 0.15 per min, respectively.
Abstract: Erythromycin binding to Escherichia coli ribosomes required K(+) and Mg(2+). Under optimal conditions, the dissociation constant for erythromycin binding to E. coli ribosomes was found to be 1.0 x 10(-8) M and 1.4 x 10(-8) M at 24 C and 5 C, respectively. One molecule of [(14)C]erythromycin was bound to each 70S ribosome at equilibrium. Binding of erythromycin to ribosomes was rapid and reversible. The specific rate constants for the forward and reverse reactions were 1.7 x 10(7) liters per mol per min and 0.15 per min, respectively.
TL;DR: The group treated once daily demonstrated a significant but reversible increase in mean serum creatinine concentration and decrease in mean creatinines clearance during therapy as compared with no change in the group treated with three injections daily.
Abstract: Patients with urinary tract infection were treated for 8 to 15 days with one daily intramuscular injection of 160 mg of gentamicin or 60 or 80 mg every 8 h. Ten of 11 patients treated with one injection daily were cured as compared with 8 of 10 patients treated with three injections daily. Urinary concentrations of gentamicin were 3.2 to 600 μg/ml in all 8-h collections in patients receiving one injection daily and were 22 to 440 μg/ml in all 8-h collections in patients receiving three injections daily. The group treated once daily demonstrated a significant but reversible increase in mean serum creatinine concentration and decrease in mean creatinine clearance during therapy as compared with no change in the group treated with three injections daily. Decreases in renal function were correlated with higher milligram per kilogram doses and higher 1-h serum concentrations.