Search tips
Search criteria

Results 1-25 (281)

Clipboard (0)
Year of Publication
Document Types
9.  In Vitro Studies with Cefazolin 
Susceptibilities of 259 isolates of pathogenic bacteria to cefazolin were measured by broth and agar dilution procedures. Beta-hemolytic streptococci were inhibited by 0.25 μg/ml, whereas Staphylococcus aureus and alphahemolytic streptococci were inhibited by 2.0 μg/ml. Enterococci were resistant to less than 32 μg/ml. Wide variation was seen with gram-negative species. Most isolates of Klebsiella species and Proteus mirabilis were inhibited by 4.0 or 8.0 μg/ml. Escherichia coli were less susceptible, and most isolates of Pseudomonas aeruginosa, Serratia species, and Enterobacter species were resistant to 128 μg/ml.
PMCID: PMC444750  PMID: 4451358
10.  Morphological Alterations of Pseudomonas aeruginosa by Ticarcillin: a Scanning Electron Microscope Study 
Pseudomonas aeruginosa was exposed to 0.1, 1.0, 10, 100, and 1,000 times the minimal inhibitory concentration of ticarcillin in vitro and subsequently examined with the scanning electron microscope. The morphological alterations observed were filamentation, mid-cell defects, and spheroplast formation, and these alterations were dependent upon the drug concentration.
PMCID: PMC444749  PMID: 4218072
11.  Studies on the Regulation of Colicin Ib Synthesis: Replication of the Col Ib-P9 Plasmid During Colicin Induction 
The Col Ib-P9 plasmid content of colicinogenic cells has been measured by both sedimentation analysis of cleared lysates and by deoxyribonucleic acid hybridization to purified Col Ib-P9 factor deoxyribonucleic acid. The results show an independence between mitomycin C-induced colicin synthesis and Col Ib-P9 replication. In addition, the ratio of the various molecular configurations (i.e., covalently closed circles or open circles) of the Col Ib-P9 plasmid does not change upon induction of colicin synthesis. Heat treatment of a colicinogenic strain carrying a thermosensitive dnaB mutation on the bacterial chromosome leads to complete inhibition of Col Ib-P9 plasmid replication and the simultaneous induction of colicin Ib synthesis in all cells of the colicinogenic population. These studies rule out mechanisms or regulation of colicin Ib synthesis based on the induced replication of the Col Ib-P9 plasmid. Our studies show that in a Col Ib-P9 colicinogenic population there is, on the average, one plasmid per cell.
PMCID: PMC444748  PMID: 4451357
12.  Properties of R Factors from Bordetella bronchiseptica 
Genetic properties and host ranges of R factors derived from Bordetella bronchiseptica of pig origin were examined. All of 61 R factors tested could confer resistance to streptomycin, sulfonamide, and aminobenzyl penicillin on their host bacteria. All of them were identified as fi− (no fertility inhibition) type and were found to exhibit no restriction of phages λ, φ80, P1, P2, T1, T3, T6, T7, W31, and BF-23. They could confer macarbomysin susceptibility on their host cells when infected. An Rte16, a representative R factor, was incompatible with both RP4 and R40a, which are classified as compatibility groups P and C, respectively. An Rte16 was conjugally transmissible to B. bronchiseptica, Escherichia coli, Citrobacter freundii, Salmonella typhimurium, and Yersinia enterocolitica, but not to Shigella flexneri, S. sonnei, Proteus mirabilis, P. vulgaris, P. rettgeri, Klebsiella pneumoniae, and Pseudomonas aeruginosa.
PMCID: PMC444746  PMID: 4451355
13.  Simple Assay for Clindamycin in the Presence of Aminoglycosides 
The presence of aminoglycoside antibiotics interferes with the determination of clindamycin levels by standard microbiological assay. A new bioassay method of quantitation of clindamycin in the presence of aminoglycosides is presented. This technique is based on the fact that incorporation of calcium chloride into assay agar blocks the antimicrobial activity of aminoglycosides against Sarcina lutea but allows the assay of as little as 0.31 μg of clindamycin per ml. The error of the system is less than 10%. This method is simple and adaptable to existing assay systems for clindamycin.
PMCID: PMC444745  PMID: 4451354
14.  Evidence for Participation of Autolysins in Bactericidal Action of Oxacillin on Staphylococcus aureus 
A comparison of the autolytic enzyme activity in Staphylococcus aureus strains that differ markedly in their rates of lysis and killing after exposure to oxacillin has been made. Log-phase cells of the clinical isolate that is tolerant to oxacillin inhibition were found to contain a level of autolytic enzyme activity comparable to that in a sensitive strain. This autolysin from log-phase cells was recovered after a single freeze-thaw cycle and assayed by using both native and penicillin (un-cross-linked) mureins. These same assays, however, revealed a significant difference in autolysin activity extractable from the two strains if the cells were inhibited by oxacillin. Under these conditions, the S. aureus strain that is susceptible to the killing and lytic effects of oxacillin had considerably more activity on penicillin murein than did the tolerant organism. These results provide evidence that hydrolytic enzymes on the cell surface are required to augment the wall damage initiated by oxacillin and other β-lactam antibotics to produce a bactericidal effect.
PMCID: PMC444744  PMID: 4498775
15.  Phosphorylation of Kanamycin, Lividomycin A, and Butirosin B by Providencia stuartii 
The isolation of Providencia stuartii resistant to multiple aminoglycoside antibiotics prompted an investigation into the mechanism of their resistance. Crude enzyme extracts of a strain of P. stuartii inactivated kanamycin, lividomycin A, and butirosin B in the presence of adenosine 5′-triphosphate (ATP), as measured by a microbiological assay. The occurrence of inhibitory concentrations of 500 μg or greater per ml against kanamycin, lividomycin A, and butirosin B, coupled with the inactivation of these antibiotics in the presence of ATP, suggested enzymatic phosphorylation. This was documented by the transfer of the γ-phosphate of [γ-32P]ATP. In contrast, the inability to inactivate gentamicin or tobramycin by the crude enzyme extracts in the presence of ATP suggests another enzymatic mechanism of resistance for these antibiotics, such as adenylation or acetylation. Of importance is the fact that amikacin, a semisynthetic analogue of kanamycin A which is resistant to inactivation by most resistance transfer factor enzymes, was found to inhibit the growth of P. stuartii at low concentrations.
PMCID: PMC444743  PMID: 4455126
16.  Penicillin: Reversible Inhibition of Forespore Septum Development in Bacillus megaterium Cells 
Benzylpenicillin inhibits the development of the forespore septum in sporulating Bacillus megaterium cells. The inhibitory effect is a function of the duration of exposure to the antibiotic and is completely reversible by penicillinase. Under the incubation conditions employed, less than 20% of the covalently bound antibiotic is released from the cells. The penicillin which remains bound to the cells after treatment with penicillinase may be necessary but is not sufficient for the effect; unbound antibiotic in the sporulation medium is also required.
PMCID: PMC444742  PMID: 4217587
17.  Rapid, Precise, Turbidometric Assay for Low Levels of Ampicillin in Serum After Single-Dose Oral Administration 
A turbidometric assay is described for the quantitative measurement of ampicillin in serum. Standard curves prepared with known concentrations of ampicillin in serum exhibited acceptable linearity over a concentration range of approximately 0.2 to 1.8 μg/ml. Data are presented to show the excellent precision of the assay and the application of the assay to clinical studies. The advantages of this method over other procedures are discussed. Because of the questionable stability of ampicillin, samples containing known concentrations of ampicillin in serum were assayed after storage for various lengths of time. Serum samples maintained in the frozen state until the time of assay exhibited approximately 12% degradation after 7 days, whereas those samples which were subjected to repeated thawing and refreezing exhibited approximately 25% degradation after the same time interval.
PMCID: PMC444741  PMID: 4451353
18.  Properties of an R Plasmid in Pseudomonas aeruginosa Producing Amikacin (BB-K8), Butirosin, Kanamycin, Tobramycin, and Sisomicin Resistance 
Pseudomonas aeruginosa strain GN315, producing kanamycin acetyltransferase, can transmit a plasmid determining resistance to kanamycin, amikacin (BB-K8), butirosin, tobramycin, and sisomicin, but not gentamicin, to other pseudomonas strains. This plasmid, pMG5, belongs to the same incompatibility group as plasmids determining gentamicin resistance in P. aeruginosa via gentamicin acetyltransferase I. Like other members of this group, it also confers resistance to Hg2+, organomercurials, and certain deoxyribonucleic acid phages. When pMG5 is introduced into a cell carrying a related R factor, some transconjugants can subsequently cotransfer new combinations of resistance determinants as though recombinant plasmids had been formed.
PMCID: PMC444740  PMID: 4217586
19.  Enhancement of the Effects of Anti-Staphylococcal Antibiotics by Aminoglycosides 
The in vitro activity of seven anti-staphylococcal antibiotics alone and in combination with four aminoglycoside antibiotics against 35 clinical isolates of Staphylococcus aureus from blood cultures of patients with endocarditis or septicemia was studied. The combination of nafcillin-gentamicin or nafcillin-tobramycin when compared with nafcillin alone killed significantly more S. aureus at 6 h for 33 of 35 isolates. A significant decrease in viable colony-forming units at 24 and 48 h was demonstrated for a smaller number of isolates. Using the agar dilution antibiotic susceptibility test, significant enhancement of activity was demonstrated against almost all isolates when cephalothin, cefazolin, or clindamycin was combined with gentamicin, tobramycin, or kanamycin. The combination of nafcillin or vancomycin with gentamicin, tobramycin, or kanamycin also showed enhanced activity against the majority of isolates. Oxacillin or methicillin when combined with the aminoglycosides showed enhancement of activity against the least number of isolates. Streptomycin was the least effective of the four aminoglycoside antibiotics studied.
PMCID: PMC444739  PMID: 4451352
20.  Characterization and Prevalence of the Different Mechanisms of Resistance to Beta-Lactam Antibiotics in Clinical Isolates of Escherichia coli 
A survey of clinical isolates from a hospital laboratory showed that Escherichia coli could be grouped into three classes of beta-lactam-antibiotic resistance by results of routine susceptibility testing to ampicillin, cephalothin, and carbenicillin. E. coli highly resistant to ampicillin and carbenicillin but not to cephalothin (class I) were found to have one of two levels of R factor-mediated, periplasmic-β-lactamase which resembled RTEM and was located behind a permeability barrier to penicillins but not to cephalosporins. This permeability barrier appeared to act synergistically with the β-lactamase in producing high levels of resistance to penicillins. E. coli highly resistant to ampicillin and cephalothin but not carbenicillin (class II) were found to have a β-lactamase with predominantly cephalosporinase activity which was neither transferable nor releasable by osmotic shock. E. coli moderately resistant to one or to all three of these antibiotics (class III) were found to have low levels of different β-lactamases including a transferable β-lactamase which resembled R1818. Thus, different mechanisms producing resistance to β-lactam antibiotics could be deduced from the patterns of resistance to ampicillin, cephalothin, and carbenicillin found on routine susceptibility testing. E. coli of class I were much more prevalent than the other classes and the proportion of E. coli that were class I increased with duration of patient hospitalization. The incidence of class I E. coli rose only slightly over the past 7 years and that of class II E. coli remained constant despite increased usage of both cephalothin and ampicillin. These observations emphasize that the properties of the apparently limited number of individual resistance mechanisms that exist in a bacterial flora, such as their genetic mobility and linkages and the spectrum of their antibiotic inactivating enzymes and permeability barriers, may govern the effect that usage of an antibiotic has upon the prevalence of resistance to it and to other antibiotics.
PMCID: PMC444738  PMID: 4615632
21.  In Vitro Inhibition of Coccidioides Immitis Strains with Amphotericin B Plus Rifampin 
Rifampin was shown in vitro to decrease the amphotericin B minimal inhibitory concentrations of all of 10 strains of Coccidioides immitis tested. These decreases ranged from two- to fourfold and occurred with rifampin concentrations of 10 to 40 μg/ml. Rifampin alone was without effect.
PMCID: PMC444736  PMID: 4451350
22.  Characterization of the Binding of Amphotericin B to Saccharomyces cerevisiae and Relationship to the Antifungal Effects 
Based on the enhanced fluorescence of amphotericin B in acid solutions, a quantitative assay for this polyene antibiotic has been developed that is sensitive and linear in the range of 0.1 to 10.0 μM. The binding of amphotericin B to Saccharomyces cerevisiae was assayed under various conditions as the amount bound to cells in a dialysis chamber or after centrifugation. Two types of binding were defined: weak, reversible binding occurred at 0 C or higher temperatures and even in the presence of inhibitors of energy metabolism, whereas strong, irreversible binding did not occur at 0 C and was inhibited when energy metabolism was blocked. Only strong binding was correlated with cell killing. Weak binding probably involves the outer layer of the membrane; strong binding probably requires disruption of hydrophobic regions of the cell membrane.
PMCID: PMC444734  PMID: 4615631
23.  Endogenous, Spontaneous Formation of Beta-Lactamase in Staphylococcus aureus 
In a β-lactamase-inducible strain of Staphylococcus aureus, the enzyme appears spontaneously in the absence of added inducer during lag and early log phases of growth and then declines rapidly to low levels. The endogenous inducer responsible for appearance of the enzyme has been isolated and purified and characterized as a peptidoglycan, containing muramic acid, glucosamine, glutamic acid, alanine, lysine, and glycine. The inducing compound could be isolated from the cells only during the lag and early log phases and from no other later periods. The data obtained are consistent with the thesis advanced earlier from this laboratory that β-lactamase serves a cellular function in the producing cell more important and beyond its capability of hydrolyzing certain penicillins to the antibiotically inactive penicilloic acids.
PMCID: PMC444733  PMID: 4451348
24.  Chloroquine-Resistant Plasmodium falciparum: Effect of Substrate on Chloroquine and Amodiaquin Accumulation 
Glucose stimulates the high-affinity processes of chloroquine and amodiaquin accumulation in owl monkey erythrocytes infected with a chloroquine-susceptible strain of Plasmodium falciparum. Although these erythrocytes have greater ability to accumulate amodiaquin than chloroquine, glucose has relatively less effect on amodiaquin accumulation than on chloroquine accumulation. In contrast to these findings with chloroquine-susceptible P. falciparum, glucose stimulates amodiaquin but not chloroquine accumulation in erythrocytes infected with chloroquine-resistant P. falciparum. This lack of function of a substrate-dependent component of chloroquine accumulation distinguishes chloroquine-resistant from chloroquine-susceptible P. falciparum.
PMCID: PMC444732  PMID: 4217585
25.  Evaluation of Bis-Benzimidazoles in the Treatment of Murine Lymphocytic Choriomeningitis Virus Infections 
Seventy percent of the mice receiving (S,S)-1,2-bis(5-methoxy-2-benzimidazolyl)-1,2-ethandiol (A36683) in their drinking water lived at least four times longer than control mice when infected with 10 or 100 mean lethal doses of lymphocytic choriomeningitis virus strain UBC. In the next 4 months, most of the survivors died with lymphocytic choriomeningitis-like symptoms. Drug treatment during the first 7 days after infection was found to have no significant effect on virus titers in various organs. The sparing effect of the drug is discussed in terms of immunosuppression.
PMCID: PMC444731  PMID: 4451347

Results 1-25 (281)