In vitro and in vivo activity of azithromycin (CP 62,993) against the Mycobacterium avium complex.
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Animals↗
Biomedical subjects
C B Inderlied
Publications and source records attributed to C B Inderlied.
Bacteriostatic and bactericidal in-vitro activity of meropenem against clinical isolates, including Mycobacterium avium complex.
For clinical isolates the MICs of meropenem were significantly lower than the MICs of imipenem, especially against Pseudomonas aeruginosa. Furthermore, meropenem was bactericidal for Pseudomonas spp., including Ps. (Xanthomonas) maltophilia, and staphylococci, with MBCs on average only two-fold above the respective MICs. The bactericidal activity was confirmed by killing curve assays. Strains with high meropenem MICs (greater than or equal to 8 mg/l) were killed by a combination of the carbapenem and amikacin, with kinetics that indicated synergism between the two antimicrobial agents.
Amikacin↗
Amikacin, ciprofloxacin, and imipenem treatment for disseminated Mycobacterium avium complex infection of beige mice.
The Mycobacterium avium complex (MAC) is a common cause of disseminated infection in patients with acquired immunodeficiency syndrome and is increasingly seen as a cause of infection in other immunocompromised patients. Traditional antimycobacterial therapy often is ineffective, and there is a clear need for antibiotics with proven activity against the MAC. Three agents, amikacin, ciprofloxacin, and imipenem, were tested in vitro for activity against MAC strain 101. Amikacin was bacteriostatic, with an MIC of 4.8 micrograms/ml, which is significantly lower than the concentration in serum obtained with standard dosing. Imipenem and ciprofloxacin had little or no activity alone (MICs, greater than 16 and 4.7 micrograms/ml, respectively), but when they were combined with amikacin there was bactericidal activity. Each agent was tested individually and in combination by using the beige mouse model of disseminated MAC infection. There was no mortality in a group of animals infected with MAC 101 and treated with amikacin alone; also, there was a significant decrease in the infection of the blood, liver, and spleen. There was no apparent improvement in therapeutic effectiveness when amikacin was combined with the other agents. Neither ciprofloxacin nor imipenem was active as a single agent, which was consistent with the in vitro activities of these agents. Amikacin in combination with traditional antimycobacterial agents warrants further study as potential therapy for disseminated MAC infections.
Amikacin↗
Diagnostic efficacy of a nasotracheal protected specimen brush in patients with suspected bacterial pneumonia.
The diagnostic yield and safety of a novel nasotracheal protected specimen brush (PSB) were evaluated in 15 nonintubated adult patients with suspected bacterial pneumonia. A double-catheter PSB was passed directly through the anesthetized nose and into the trachea without bronchoscopy or fluoroscopy. Endotracheal brushing was performed in less than 10 sec, and the brush was immediately processed for Gram staining and quantitative aerobic and anaerobic cultures. According to clinical follow-up and response to therapy, 11 episodes of bacterial pneumonia and five cases of nonbacterial lung disease were established. The PSB Gram stain confirmed lower respiratory sampling in all cases. The PSB cultures indicated respiratory pathogens in 9/11 (82%) cases of pneumonia, with greater than 10(3) colony-forming units (cfu)/ml in all but two specimens. All patients with pneumonia responded to specific antibiotics. All patients with nonbacterial disorders had PSB cultures of less than 10(3) CFU/ml, and their pulmonary processes improved without antibiotic therapy. The procedure was well tolerated, although two patients had transient bronchospasm or apnea. Experience with the nasotracheal PSB is limited, but the procedure appears to be a reliable and relatively safe alternative diagnostic method in selected patients with suspected bacterial pneumonia. Quantitative cultures are necessary to improve its diagnostic accuracy.
Adult↗
Activity of ciprofloxacin and other fluorinated quinolones against mycobacteria.
The new fluorinated quinolones display interesting but variable activity against mycobacteria. Almost all compounds tested (ciprofloxacin, ofloxacin, enoxacin, norfloxacin, difloxacin, CI-934, A-56620, and megalone) inhibit Mycobacterium tuberculosis at achievable serum concentrations, with ciprofloxacin and ofloxacin most active by weight (minimal inhibitory concentration at which growth of 90 percent of strains is inhibited is equal to 1 microgram/ml or less). The growth of Mycobacterium kansasii, Mycobacterium xenopi, and Mycobacterium fortuitum is also well inhibited by these agents in the same range of concentrations. Activity against the Mycobacterium avium complex is method-dependent, with growth of perhaps one third of the strains isolated from patients with the acquired immune deficiency syndrome inhibited by ciprofloxacin. Determination of individual drug efficacy data in experimental mycobacterial infections is not a practical goal. However, combination therapy studies are in progress using murine models of both M. tuberculosis and M. avium challenges. Ofloxacin has been used with some success in human patients with pulmonary tuberculosis. Oral administration may be an important advantage, and, when used in combination with other active agents, the new quinolones may have a useful role in treating mycobacterial infections.
Anti-Bacterial Agents↗
Determination of in vitro susceptibility of Mycobacterium avium complex isolates to antimycobacterial agents by various methods.
Various methods were used to determine the in vitro susceptibility of Mycobacterium avium complex strains isolated from patients with acquired immunodeficiency syndrome. Our results confirm the noted resistance of the M. avium complex to conventional antituberculosis agents. The procedures used were both agar dilution and broth dilution, including a commercially available radiometric system (BACTEC; Johnston Laboratories, Towson, Md.). In general, all strains were more resistant by an agar dilution procedure than by a broth dilution procedure. Radiometric data were analyzed by defining a value, termed T100, which provides a discrete MIC. The broth (radiometric) procedure is reproducible and convenient for screening antimicrobial agents for in vitro activity and assessing potential therapeutic efficacy. Nevertheless, there is no standard procedure for determining the in vitro susceptibility of the M. avium complex, and appropriate clinical correlation studies are needed to accurately assess the clinical relevance of any in vitro result.
Amikacin↗
Confirmation of the beige mouse model for study of disseminated infection with Mycobacterium avium complex.
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Acquired Immunodeficiency Syndrome↗
Effect of the source of Mueller-Hinton agar and resistance frequency on the detection of methicillin-resistant Staphylococcus aureus.
Inconsistencies in the results of disk diffusion tests of oxacillin against Staphylococcus aureus that occurred when using commercially prepared Mueller-Hinton agar from different sources led us to evaluate the ability of media from different sources to detect resistance to oxacillin, methicillin, and nafcillin in S. aureus. Mueller-Hinton agar from five manufacturers was prepared in our laboratory and used for standard disk diffusion and agar dilution tests. Ten oxacillin-resistant S. aureus isolates, of which three were definitive-resistant and seven were occult-resistant, were examined. All definitive-resistant strains were resistant to all three antimicrobial agents on four out of five agars. The occult-resistant strains were consistently detected as resistant on only one of the agars. With only slight differences, oxacillin, methicillin, and nafcillin resistance was more readily detected by disk diffusion and agar dilution when initially incubated at 30 degrees C, and extended incubation improved the detection. The frequency of resistance within a population of occult-resistant cells was low compared with the frequency within a population of definitively resistant cells. The heterogeneity of colony morphology and apparent growth rates within a population of occult-resistant cells contributed to the problem of detecting some resistant isolates. Definitive-resistant isolates were characterized by a very high and stable frequency of resistance. Occult-resistant strains were characterized by a lower frequency of resistance, although the true frequency of resistance may be difficult to ascertain because of heterogeneity in growth rates.
Agar↗
Detection of antibody to Staphylococcus aureus teichoic acid by enzyme-linked immunosorbent assay.
A sensitive, specific, and rapid enzyme-linked immunosorbent assay has been developed for the detection of immunoglobulin G to Staphylococcus aureus teichoic acid in human sera. Detection of S. aureus teichoic acid antibody is at least 800 times more sensitive than a double diffusion in gel assay, and positive titers of 1:25,600 and greater were observed with this assay. Results with the enzyme-linked immunosorbent assay can be obtained within 3.5 h by using antigen-coated cuvettes. Quantitation of S. aureus teichoic acid antibody by this enzyme-linked immunosorbent assay may be useful in the initial as well as the follow-up diagnosis of serious S. aureus infections.
Antibodies, Bacterial↗
Conditions for the chemical and physical inactivation of the K. Fu. strain of the agent of Creutzfeldt-Jakob disease.
The unusual resistance of the "unconventional viruses" to inactivation by the commonly used disinfectants has led to a high degree of apprehension regarding patients with any form of dementia. The rapid adaptation of a newly acquired isolate of the agent of Creutzfeldt-Jakob Disease (CJD) to mice made possible this large scale study of its heat and chemical stability. The agent showed a decrease in titer of approximately two logs following incubation at 80 degrees C for 30 minutes with no additional loss at 80 degrees C for up to 500 minutes. There was greater than a three log decrease in titer at 100 degrees C for 30 minutes and temperatures of 115 degrees and 130 degrees C completely inactivated the agent. Treatment with sodium hypochlorite at three concentrations (0.33 per cent, 0.66 per cent and 1.31 per cent) showed inactivation of greater than 99 per cent at each. Crude agent preparations were not inactivated by sodium dodecylsulfate at detergent to protein ratios up to 4:1. These results suggest that those hospital supplies which resist autoclaving may be adequately disinfected by autoclaving for at least 30 minutes. Treatment of surfaces with solutions of sodium hypochlorite (household bleach) at concentrations of 15 to 25 per cent is also effective. Detergent treatment of contaminated surfaces or materials is inadequate for proper decontamination.
Animals↗
Lipid synthesis during morphogenesis of Mucor racemosus.
Lipid synthesis increases coordinately with protein and RNA synthesis during morphogenesis of Mucor racemosus. The lipid synthesis inhibitor cerulenin can completely block morphogenesis under conditions in which cell growth continues. An increase in phospholipid turnover may be an important correlate to morphogenesis of Mucor spp., especially the turnover of phosphotidyl inositol and phosphatidyl ethanolamine. The increase in ornithine decarboxylase, which occurs during morphogenesis, is inhibited by the addition of cerulenin.
Acetates↗
Regulation of ornithine decarboxylase during morphogenesis of Mucor racemosus.
During the yeast-to-hyphae transition of the dimorphic phycomycete Mucor racemosus, there was a 30- to 50-fold increase in the activity of ornithine decarboxylase. Increased enzyme activity preceded the emergence of germ tubes and reached a maximum before conversion was completed. Subsequently, enzyme levels rapidly declined, despite the continuation of mycelial growth. Both putrescine and spermidine blocked the enzyme activity response. Protein synthesis was required for the increase in enzyme activity during morphogenesis. A combination of actinomycin D and netropsin inhibited ribonucleic acid synthesis but failed to inhibit the increase in ornithine decarboxylase activity. There was a twofold increase in the enzyme half-life during morphogenesis with either trichodermin or verrucarin to inhibit protein synthesis.
Carboxy-Lyases↗
Differential synthesis of polypeptides during morphogenesis of Mucor.
The extent of differential gene expression during morphogenesis of Mucor racemosus was investigated by two-dimensional polyacrylamide gel electrophoresis of neutral and acidic polypeptides. Cellular proteins were labeled with [35S]methionine in cells growing in either the yeast or hyphal form, or in yeast cells undergoing the transition of hyphae. The results showed that of the 400 to 500 polypeptides resolved by electrophoresis, relatively few were specific to one or the other morphological form. The major change in the patterns of proteins synthesized during morphogenesis was a change in rates of synthesis of individual polypeptides. Experiments in which morphogenesis was affected under aerobic or anaerobic conditions showed that the majority of changes in the protein patterns were associated with morphogenesis and were not a specific response to O2.
Anaerobiosis↗
Glucose metabolism and dimorphism in Mucor.
Mucor racemosus fermented glucose to ethanol, carbon dioxide, and glycerol. When this fungus was grown anaerobically in either the yeast or mycelial form, the catabolism of glucose was very similar. Yeast cells shifted to aerobic conditions maintained a high flux of glucose carbon through the glycolytic and pentose phosphate pathways. Mycelial cells grown aerobically catabolized glucose in a manner consistent with a respiratory metabolism. Although there was no consistent pattern of glucose metabolism in the mycelial form of Mucor, growth in the yeast form consistently was correlated with a high flux of glucose carbon through the catabolic pathways.
Fermentation↗
Growth of Klebsiella aerogenes on xylitol: implications for bacterial enzyme evolution.
When Klebsiella aerogenes was grown in continuous culture with xylitol. an unnatural pentitol, as the growth limiting substrate, the structural gene which codes for ribitol dehydrogenase, an enzyme which gratuitously catalyzes the oxidation of xylitol to D-xylulose, was duplicated. It appears that the duplication mechansim only duplicates the gene which is subjected to selective pressure and not any of the other closely linked genes. The degree to which the ribitol dehydrogenase gene is duplicated does not appear to be strictly correlated with the ability to grow faster on xylitol. Duplication mutants do, in fact, grow faster than their parent strain, but when challenged to grow at even higher growth rates there is a catabolic repression of enzyme activity. Thus a situation is created in which a structural gene is duplicated in response to selective pressure; these mutants can grow faster on the new substrate, but faster growth results in a "silencing" of a portion of the genes by catabolite repression.
Alcohol Oxidoreductases↗
Nitrate reduction and the growth of Veillonella alcalescens.
Veillonella alcalescens, a strict anaerobe, was found to possess a nitrate reductase system which has characteristics of both assimilatory and respiratory nitrate reduction. The nitrate reductase has been identified tentatively as a particulate enzyme which utilizes a variety of electron donors for the reduction of nitrate. By use of (15)N-labeled nitrate, it was shown that under appropriate conditions nitrate nitrogen is incorporated into cell material. V. alcalescens grown on pyruvate and nitrate has a greater growth rate than cells grown on pyruvate alone. Growth can occur in a medium with hydrogen and nitrate as the sole energy source. Ammonium chloride decreases the rate of nitrate reduction but does not completely inhibit reduction or incorporation. The results suggest that nitrate assimilation and respiration are not as distinct as in some other organisms.
Ammonium Chloride↗
In vitro activity of lomefloxacin as compared with ciprofloxacin.
Lomefloxacin (SC47111, Searle) is a difluorinated quinolone with a comparatively long half-life and high serum concentration. This agent has good in vitro activity against Enterobacteriaceae (MIC90 = less than 2 micrograms/ml) and staphylococci (MIC90 = less than 2 micrograms/ml); the activity against Pseudomonas spp. and Pseudomonas aeruginosa is moderate to poor. On a weight basis, lomefloxacin is less active than ciprofloxacin; however, based on the ratio of the serum concentration to MIC, the activity of lomefloxacin is nearly equivalent to ciprofloxacin against many bacteria, with the exception that ciprofloxacin has good activity against most pseudomonads. Also, lomefloxacin was active against a variety of bacteria that were resistant to aminoglycosides and/or third-generation cephalosporins. A majority of strains of the Mycobacterium avium complex, isolated from AIDS patients with disseminated disease, were found to be resistant to lomefloxacin (MIC90 = greater than 8 micrograms/ml).
Acquired Immunodeficiency Syndrome↗
Practical issues in the antibiotic and immunotherapy of Mycobacterium avium disease in immunocompromised patients.
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AIDS-Related Opportunistic Infections↗