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Biomedical subjects

R C Moellering

Publications and source records attributed to R C Moellering.

At least 109 records · Page 6Linked to original sources
PubMed1988

Mechanism of action and in vitro and in vivo activities of S-6123, a new oxazolidinone compound.

The in vitro activity of S-6123, a synthetic antimicrobial compound of the new oxazolidinone series, was compared with those of other orally administered agents against 328 clinical isolates. The compound was moderately active (MICs, 16 to 64 micrograms/ml) against 90% of staphylococci, nonenterococcal streptococci, and Haemophilus influenzae, including strains resistant to beta-lactam antibiotics. S-6123 was minimally active against enterococci and facultative gram-negative bacilli. Nevertheless, the compound had significant activity in a lethal rat Escherichia coli peritonitis model at serum concentrations of one-tenth the MIC against the infecting organism. The drug demonstrated only bacteriostatic activity against susceptible organisms. Studies to define the mechanism of antibacterial action revealed that S-6123 inhibited ribosomal protein synthesis without inhibiting DNA or RNA synthesis. This compound represents a new series of antibacterial agents not related to any other antibacterial compound of natural or synthetic origin.

Animals↗
PubMed1988

Multiply high-level-aminoglycoside-resistant enterococci isolated from patients in a university hospital.

Enterococci isolated from different body sites were tested for high-level gentamicin resistance. A total of 259 enterococcal isolates were screened for resistance (MIC, greater than 2,000 micrograms/ml) by a broth-tube method. Thirty-nine (15.1%) were found to exhibit resistance and were confirmed by agar screening (1,000 micrograms/ml) and agar dilution MIC determinations. The majority of isolates also showed high-level resistance to kanamycin and streptomycin. The remaining isolates showed high-level resistance to gentamicin and kanamycin but not streptomycin. Synergy testing of several isolates confirmed the correlation between lack of synergy and high-level resistance. A retrospective clinical review was performed. Most patients had a source of definite or likely infection (79%). Serious infections such as endocarditis or meningitis were not observed during the course of this study. Retrospective clinical data suggest that in cases not involving endocarditis or meningitis, neither infection refractory to therapy nor relapse of infection is a common sequela of infection with gentamicin-resistant enterococci in hospitalized patients.

Anti-Bacterial Agents↗
PubMed1987

In vitro evaluation of the new paulomycin antibiotic paldimycin.

The comparative in vitro activity of paldimycin, a new antibiotic, was evaluated against 215 gram-positive bacteria. Activity of the compound was greater in nutrient agar of pH 6.8 than in Mueller-Hinton agar. All strains of staphylococci, streptococci, enterococci and Listeria monocytogenes were inhibited at concentrations less than or equal to 2 micrograms/ml. Activity of the new drug was generally comparable to that of vancomycin.

Acetylcysteine↗
PubMed1987

Comparative in-vitro activity of A-56268 (TE-031), a new macrolide antibiotic.

The comparative in-vitro activity of A-56268 (TE-031), a new semisynthetic macrolide antibiotic, was assessed against approximately 400 bacterial isolates. The new drug demonstrated excellent activity against penicillin-susceptible streptococci (MIC90s less than or equal to 0.06 mg/l) and methicillin-susceptible staphylococci (MIC90 = 0.25 mg/l). Among other Gram-positive organisms tested, a significant number were resistant to A-56268 as well as to erythromycin and clindamycin. A-56268 was at least as active as erythromycin against Pasteurella multocida and Campylobacter jejuni, but was more active than erythromycin against Legionella spp. (MIC90 less than or equal to 0.06 mg/l), Bacteroides fragilis (MIC90 = 4 mg/l) and Bact. melaninogenicus (MIC90 less than or equal to 0.125 mg/l). Activity of A-56268 was pH dependent (more active at pH 7 than at pH 6) and was moderately affected by inoculum size. The drug was bactericidal against two strains of Streptococcus pyogenes tested, but exerted a bacteriostatic effect against Staphylococcus aureus and Str. faecalis.

Anti-Bacterial Agents↗
PubMed1987

In vitro activities of ICI 194008 and ICI 193428, two new cephem antimicrobial agents.

The in vitro activities of two new cephem antibiotics, ICI 193428 and ICI 194008, were compared with those of cefpirome, cefotaxime, ceftazidime, and piperacillin. Essentially all strains of the family Enterobacteriaceae were inhibited by both study drugs at concentrations of less than or equal to 4 micrograms/ml. Both new cephems were comparable to ceftazidime against Pseudomonas aeruginosa (MIC for 90% of strains, 8 micrograms/ml) and were the most active agents tested against Pseudomonas maltophilia (MIC for 90% of strains, 16 micrograms/ml).

Anti-Bacterial Agents↗
PubMed1987

Continuous-infusion ampicillin therapy of enterococcal endocarditis in rats.

Intermittent administration of ampicillin alone has resulted in high failure rates in previously described animal models of enterococcal endocarditis. We developed a rat model of enterococcal endocarditis which permits comparison of continuous intravenous infusion of ampicillin with intramuscular therapy. Continuous low-dose ampicillin infusion (450 mg/kg [body weight] per day) was compared with the same dose given intramuscularly in three divided doses and with high-dose infusion (4.5 g/kg per day) of the drug. For the infecting strain of Streptococcus faecalis, the MIC and MBC were 1 microgram/ml. Mean ampicillin levels in serum were 53.9 +/- 4.8 (peak) and less than 1 (trough), 8.7 +/- 1.4, and 244 +/- 29 micrograms/ml for intramuscular, low-dose, and high-dose regimens, respectively. Ampicillin infusion therapy significantly increased the survival rate and sterilization of blood cultures. Continuous infusions were superior to intermittent therapy in eradicating bacteremia. After 5 days of treatment, low-dose ampicillin infusion was more effective than intermittent therapy in sterilizing cardiac vegetations (P less than 0.01). Continuous-infusion therapy at either dose was significantly more effective than intramuscular injection in reducing bacterial titers in cardiac vegetations (5.4 +/- 1.0 log10 CFU/g [low dose], 4.8 +/- 0.3 log10 CFU/g [high dose], and 7.7 +/- 0.3 log10 CFU/g [intramuscular]). However, no statistically significant advantage was found for high-dose compared with low-dose ampicillin infusion in lowering bacterial titers in vegetations (P greater than 0.3).

Ampicillin↗
PubMed1987

In vitro activity of BMY-28100, a new oral cephalosporin.

The activity of BMY-28100, a new orally administered cephalosporin, was compared with those of cephalexin and cefaclor. BMY-28100 was the most active drug against Staphylococcus aureus (MIC for 90% of strains tested [MIC90], 1.0 microgram/ml), streptococci (MIC90S, less than or equal to 0.125 microgram/ml), and Klebsiella pneumoniae (MIC90, 2 micrograms/ml). The drug was active against Haemophilus influenzae and gonococci but not against other organisms generally resistant to cephem antibiotics.

Anti-Bacterial Agents↗
PubMed1987

Comparative in vitro activity of CGP 31608, a new penem antibiotic.

The in vitro activity of a new penem antimicrobial agent, CGP 31608, was compared with those of imipenem, SCH 34343, and several other antimicrobial agents against approximately 600 bacterial isolates. CGP 31608 was active against gram-positive organisms, including methicillin-susceptible Staphylococcus aureus (MIC for 90% of the isolates [MIC90], 0.25 microgram/ml) and penicillin-susceptible streptococci (MIC90s, less than or equal to 2 micrograms/ml). Penicillin-resistant streptococci (including enterococci) and methicillin-resistant S. aureus were more resistant to the penem. Activities of CGP 31608 against members of the family Enterobacteriaceae were remarkably uniform, with MIC90s of 8 to 16 micrograms/ml. CGP 31608 was at least as active as imipenem and ceftazidime and more active than piperacillin against Pseudomonas aeruginosa. Drug activity was not influenced by the presence of any of 10 plasmid-mediated beta-lactamases. Against strains of Serratia marcescens, Enterobacter cloacae, and P. aeruginosa with derepressible chromosomally mediated beta-lactamases, the presence of cefoxitin did not induce increased resistance to CGP 31608. The new drug was also active against anaerobes (MIC90s, 0.25 to 8 micrograms/ml), Haemophilus influenzae (MIC90s, 0.5 to 1.0 micrograms/ml), and Legionella spp. (MIC90, 2 micrograms/ml). CGP 31608 showed an antibacterial spectrum similar to those of imipenem and SCH 34343 (except that the latter is not active against P. aeruginosa) but was generally less potent than these drugs. However, CGP 31608 demonstrated more activity (MIC90) than imipenem against P. aeruginosa, Pseudomonas cepacia, and methicillin-resistant Staphylococcus epidermidis and S. aureus.

Anti-Bacterial Agents↗
PubMed1987

The enterococcus: "putting the bug in our ears".

High-level resistance to gentamicin among clinical isolates of enterococci has been found with increasing frequency in recent years. In this issue, Zervos and colleagues report findings from a prospective study in which they assessed the frequency of colonization and infection with such organisms at a university medical center, demonstrating probable person-to-person spread. Their findings suggest that hospitals should conduct systematic screening for enterococci with high-level resistance to gentamicin, that antimicrobial treatment habits be modified to limit the emergence of such organisms, and that rigorous infection control be practiced to minimize their spread. These observations are particularly timely because it has become clear that enterococci are extremely versatile pathogens which are both well suited for survival and capable of causing serious illness, especially in hospitalized patients treated with some of the newer broad-spectrum antibiotic agents. Enterococci with high-level resistance to gentamicin are also of growing concern because their resistance to many antibiotic agents severely limits the clinician's options for treatment.

Aminoglycosides↗
PubMed1986

Have the new beta-lactams rendered the aminoglycosides obsolete for the treatment of serious nosocomial infections?

Hospital-acquired infections are often due to multi-resistant gram-negative bacilli. When treating these infections, the physician must use potent antibiotics that have broad spectrums of activity. Aminoglycosidic aminocyclitols and the newer beta-lactam antibiotics are particularly valuable in the management of hospital-acquired infections. This article discusses the role of both classes of antibiotics in this setting.

Aminoglycosides↗
PubMed1986

Beta-lactam/aminoglycoside combinations: interactions and their mechanisms.

Combinations of beta-lactams with aminoglycosides are widely used in the therapy of infections. There are a number of theoretic advantages to using such combinations. Indeed, combinations of beta-lactams and aminoglycosides usually result in synergism or indifference and very rarely in antagonism. The mechanisms of synergism, resistance to synergism, and antagonism have been studied extensively in enterococci; further studies are necessary to define such mechanisms in other organisms.

Aminoglycosides↗
PubMed1986

In vitro activity of CI-934, a new quinolone antimicrobial, against gram-positive bacteria.

The in vitro activity of CI-934, a new quinolone antimicrobial, was compared with that of ciprofloxacin against selected gram-positive bacteria. Concentrations of CI-934 required to inhibit 90% of strains (MIC90) were twofold to eightfold lower than those of ciprofloxacin. With the exception of Streptococcus faecium, all isolates were inhibited by CI-934 at concentrations less than or equal to 1.0 microgram/ml.

Anti-Bacterial Agents↗
PubMed1986

In vitro and in vivo activity of LY 146032, a new cyclic lipopeptide antibiotic.

The in vitro activity of LY 146032, a cyclic lipopeptide antibiotic belonging to the class of agents designated A21978C, was compared with those of vancomycin, cefpirome, cefotaxime, and clindamycin against selected gram-positive bacteria. The new drug inhibited all staphylococcal isolates, including methicillin-resistant strains, at concentrations of less than or equal to 1.0 microgram/ml. The activity of LY 146032 was comparable to that of vancomycin against most streptococci, but the latter demonstrated greater potency against Streptococcus faecium and penicillin-resistant strains of pneumococci and viridans group streptococci. LY 146032 was markedly less active than vancomycin against Listeria monocytogenes (MICs for 90% of strains tested, 16 and 1.0 microgram/ml, respectively). The activity of LY 146032 was enhanced as the concentration of calcium in the test medium was increased. MBCs were within eightfold of the MIC for each of 12 strains tested. In a rat model of enterococcal endocarditis, the administration of LY 146032 resulted in increased survival and a reduction in the bacterial titer within cardiac vegetations compared with untreated control animals.

Animals↗
PubMed1985

Can the third-generation cephalosporins eliminate the need for antimicrobial combinations?

Antimicrobial combinations have been widely utilized since the beginning of the chemotherapeutic era. This is true despite the fact that the use of such combinations has a number of potential disadvantages, including (1) antibiotic antagonism; (2) an increased incidence of toxicity; (3) the emergence of multi-resistant organisms; (4) promotion of a false sense of security; and (5) increased expense. The reasons generally given for the use of such combinations include (1) antimicrobial synergism, (2) suppression of antimicrobial resistance, (3) decreased toxicity, and (4) broader coverage. Although there are clearly some situations in which synergistic combinations have been shown to be useful (such as in the treatment of enterococcal endocarditis and severe Pseudomonas infections), the use of combination therapy to reduce the emergence of resistance (excluding the treatment of mycobacterial infections and of infections in which rifampin is used) or to reduce toxicity has not met with widespread success. Indeed, most combinations are used simply to broaden the spectrum of antimicrobial coverage. The development of new penicillins and cephalosporins with broader spectra of activity has raised the distinct possibility that these drugs could be used as single agents for the treatment of most serious infections. Although comparative studies performed to date suggest that the new broad-spectrum penicillins and cephalosporins may be useful as single agents in the treatment of infections in a variety of clinical situations in which combinations are now commonly employed, additional studies enrolling greater numbers of patients are necessary to determine whether these agents can replace combination therapy. The use of single-drug therapy in the management of febrile episodes and documented infections in neutropenic patients remains problematic because of the greater likelihood of infections with organisms such as Pseudomonas aeruginosa, in which case combination therapy is often required. Earlier studies have clearly documented that combinations of antibiotics that are synergistic are more effective in treating bacteremias and other serious infections in neutropenic patients than are combinations that have failed to demonstrate synergism. Because of the increased activity of some of the newer drugs, such as ceftazidime, against P. aeruginosa it is possible that such agents could be used as monotherapy for patients with severe neutropenia. This possibility is an attractive one, but it should be studied carefully to make certain that it will not be associated with significant failure due to the emergence of resistant organisms.

Abdomen↗
PubMed1985

Antimicrobial combinations in the therapy of infections due to gram-negative bacilli.

Antimicrobial combinations are used most frequently to provide broad-spectrum coverage; however, they are also frequently employed to enhance antimicrobial activity (synergism). Although there is extensive in vitro documentation of synergism for many antibiotic combinations, a clear advantage for these combinations has been difficult to demonstrate in clinical studies. Several types of combinations have been useful in clinical medicine and frequently result in synergism. These include combinations of a cell wall-active agent with an aminoglycosidic aminocyclitol, combinations of a beta-lactamase inhibitor with a beta-lactam, and combinations of agents that inhibit sequential steps in a metabolic pathway. Given its spectrum of activity, aztreonam will often be used with clindamycin or a beta-lactam antibiotic. Combinations of beta-lactams may be synergistic via several mechanisms. However, these combinations also exhibit significant potential for antagonism when used against gram-negative bacilli and, therefore, require careful evaluation prior to clinical use.

Aminoglycosides↗
PubMed1985

In vitro activity of Sch 34343 against enterococci and other gram-positive bacteria.

The in vitro activity of Sch 34343, a new penem antibiotic, was compared with those of imipenem, vancomycin, and eight other antibiotics against gram-positive bacteria. Ninety percent of methicillin-susceptible Staphylococcus aureus and penicillin-susceptible streptococcal isolates were inhibited by Sch 34343 at concentrations of less than or equal to 0.125 micrograms/ml. Listeria monocytogenes isolates were susceptible to the penem at concentrations of less than or equal to 0.25 micrograms/ml. Penicillin-resistant pneumococci and viridans streptococci were relatively resistant to Sch 34343 (MIC for 90% of the isolates, 4 micrograms/ml), as were methicillin-resistant strains of S. aureus (MIC for 90% of the isolates, greater than or equal to 256 micrograms/ml). All 48 strains of Streptococcus faecalis were inhibited by concentrations of less than or equal to 8 micrograms of the drug per ml. Combinations of Sch 34343 with gentamicin demonstrated bactericidal synergism against 5 of 10 enterococcal strains tested in broth media and against 6 of 10 strains tested in 50% pooled human serum. The serum protein binding of Sch 34343 was ca. 65%. The antibacterial activity of Sch 34343 remained stable after 24 h of incubation at 37 degrees C in water or Dextrose-Phosphate broth. However, 63% of bioassayable activity was lost after 24 h of incubation at 37 degrees C in 50% human serum buffered with HEPES (N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid) (pH 7.4).

Anti-Bacterial Agents↗