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R C Moellering

Publications and source records attributed to R C Moellering.

At least 145 records · Page 8Linked to original sources
PubMed1982

Resistance to cefamandole: a collaborative study of emerging clinical problems.

Cefamandole resistance in five patients was studied. Microorganisms emerged resistant to cefamandole during therapy with the drug in three patients with complicated infections. This resistance was associated with an enhanced production of beta-lactamase and/or with a change in the substrates and the isoelectric focusing patterns of the enzymes. Cross-resistance to other beta-lactam antibiotics developed concurrently in isolates from these patients. Disk diffusion tests did not detect resistance to cefamandole in the pretreatment isolate from the fourth patient; this isolate produced inactivating enzymes, and resistance was detected only in broth dilution tests. In the fifth patient, infection with a cefamandole-resistant Enterobacter developed during postoperative therapy with the drug. Resistance to cefamandole in the isolate from this patient was unstable and was associated with inducible beta-lactamase activity. These examples emphasize the need for close monitoring of patients who are given cefamandole and for thorough in vitro evaluation of isolates from the patients both before and after treatment.

Adult↗
PubMed1982

Effects of azlocillin in combination with clavulanic acid, sulbactam, and N-formimidoyl thienamycin against beta-lactamase-producing, carbenicillin-resistant Pseudomonas aeruginosa.

We investigated the effects of the combination of azlocillin with the beta-lactamase inhibitors clavulanic acid and sulbactam and with N-formimidoyl thienamycin against strains of Pseudomonas aeruginosa with R-factor-mediated carbenicillin resistance. The 10 strains tested (1 R-, 9 R+) were isogenic, except for the presence of individual plasmids determining each of nine plasmid-mediated beta-lactamases found in P. aeruginosa. We utilized a checkerboard technique for testing antibiotic combinations. Low concentrations of clavulanic acid produced synergy with azlocillin against the strains producing the TEM-1, TEM-2, PSE-1, PSE-3, and PSE-4 beta-lactamases; for the strains producing the OXA-1, OXA-2, OXA-3, and PSE-2 beta-lactamases, such synergy was not found. With sulbactam, synergy was demonstrated in all strains except that producing PSE-2 beta-lactamase; for several strains, however, the concentration of sulbactam required to produce synergy was substantially higher than that for clavulanic acid. N-Formimidoyl thienamycin was highly active as a single agent against all of the strains, regardless of beta-lactamase production. The combination of N-formimidoyl thienamycin and azlocillin produced synergy against only two of the strains tested.

Azlocillin↗
PubMed1982

Resistance to beta-lactam antibiotics in Streptococcus faecium.

Clinical isolates of Streptococcus faecium are characteristically resistant to beta-lactam antibiotics. Two strains, selected for hypersusceptibility to penicillin, were derived from normally resistant isolates treated with novobiocin. These strains were also found to be hypersusceptible to other beta-lactams. Differences in beta-lactam susceptibility between the original isolates and the hypersusceptible strains could not be attributed to alterations in penicillin-binding protein affinities, and no evidence of a relative permeability barrier was found in the resistant strains. Isolated cell membranes prepared from resistant strains were found to possess two protein bands which were absent or greatly diminished in the membranes of susceptible strains. Hypersusceptibility to beta-lactam antibiotics in these strains may be due to the absence or alteration of one or more cell membrane proteins distinct from the penicillin-binding proteins of these organisms.

Anti-Bacterial Agents↗
PubMed1982

In-vivo acquisition of two different types of aminoglycoside resistance by a single strain of Klebsiella pneumoniae causing severe infection.

Multiple isolates of Klebsiella pneumoniae obtained from a patient were of the same biotype and capsular type and had three common plasmids. Initially, three isolates (from blood) were susceptible to aminoglycosides. Three other isolates, obtained after gentamicin treatment was begun, were susceptible to amikacin but resistant to gentamicin and tobramycin, produced 2"-aminoglycoside adenylytransferase, and had acquired an R-factor. A later isolate, obtained after amikacin therapy was begun, was susceptible to gentamicin and tobramycin, resistant to amikacin, was a small-colony variant, produced no aminoglycoside-modifying enzymes, and no longer contained the R-factor. In-vitro protein synthesis by ribosomes from this isolate was inhibited by amikacin whereas uptake of amikacin was markedly less than with previous isolates. Thus, this case illustrates the apparent in-vivo acquisition of plasmid-mediated resistance to gentamicin and tobramycin followed by loss of the plasmid and development of amikacin resistance due to decreased aminoglycoside uptake.

Amikacin↗
PubMed1982

Azlocillin, mezlocillin, and piperacillin: new broad-spectrum penicillins.

Three new broad-spectrum penicillins--azlocillin, mezlocillin, and piperacillin--will soon be available for clinical use. Azlocillin and piperacillin are more active than carbenicillin or ticarcillin against Pseudomonas aeruginosa. Piperacillin and mezlocillin demonstrate significant activity against the Enterobacteriaceae, including many strains of Klebsiella pneumoniae against which the older penicillins carbenicillin, ticarcillin, and ampicillin are ineffective. All three new drugs show substantial activity against anaerobes and ampicillin-susceptible gonococci and Haemophilus influenzae. Because these agents are inactivated by various beta-lactamases, most Staphylococcus aureus isolates and a number of gram-negative organisms, including some important nosocomial pathogens, will be resistant to these antibiotics. The new penicillins appear to be relatively safe and have been used successfully to treat patients with various infections; however, comparative trials have not yet established the superiority of these drugs over conventional therapeutic agents.

Azlocillin↗
PubMed1981

Resistance to antibiotic synergism in Streptococcus faecalis: further studies with amikacin and with a new amikacin derivative, 4'-deoxy, 6'-N-methylamikacin.

Streptococcus faecalis strains may resist penicillin-aminoglycoside synergy by the production of plasmid-mediated aminoglycoside-modifying enzymes. One of these enzymes, aminoglycoside 3'-phosphotransferase, has been shown to have a broad range of substrate specificity, including amikacin. We have studied a derivative of amikacin, 4'-deoxy, 6'-N-methylamikacin (BB-K311), against 11 clinical blood isolates of S. faecalis. Minimal inhibitory concentrations of BB-K311 were quite similar to those of amikacin, ranging from 125 to 1,000 micrograms/ml. In assays for antibiotic synergy, penicillin and amikacin produced enhanced killing compared with the penicillin alone only against those three strains which lacked the phosphotransferase enzyme. The other eight enzyme-positive strains actually demonstrated significant antagonism between penicillin against all 11 strains, regardless of enzyme production. Analysis of substrate profiles with crude preparations of the aminoglycoside 3'-phosphotransferase enzyme confirmed that BB-K311 was a very poor substrate for modification, as expected from the synergy studies. Use of other aminoglycoside analogs confirmed the 3'-OH site of modification. These findings suggest that removing the 4'-OH group in amikacin effectively blocks 3'-phosphorylation by S. faecalis enzyme.

Amikacin↗
PubMed1981

Susceptibility of enterococci and Listeria monocytogenes to N-Formimidoyl thienamycin alone and in combination with an aminoglycoside.

The susceptibilities of 12 strains of enterococci and 10 stains of Listeria monocytogenes to N-formimidoyl thienamycin were determined by a standard broth dilution method. Minimal inhibitory concentrations for L. monocytogenes strains were less than 0.25 micrograms/ml. As a group, strains of Streptococcus faecium were less susceptible than Streptococcus faecalis strains, but even for the latter, the minimal inhibitory concentrations were slightly greater than those previously reported. Minimal bactericidal concentrations against all organisms were many-fold higher than the corresponding inhibitory concentrations. In time-kill studies, combinations of N-formimidoyl thienamycin with gentamicin were synergistic against (or they completely sterilized cultures of) all the enterococcal strains and nine to 10 strains of L. monocytogenes. The magnitude of killing by the combinations was comparable to that previously observed with penicillin-gentamicin combinations. N-Formimidoyl thienamycin-tobramycin combinations were synergistic against those strains of S. faecalis and L. monocytogenes tested, but not against those of S. faecium.

Aminoglycosides↗
PubMed1981

Susceptibility of pneumococci to 14 beta-lactam agents: comparison of strains resistant, intermediate-resistant, and susceptible to penicillin.

To measure the susceptibility of penicillin-resistant pneumococci to newer beta-lactam agents, we evaluated 54 selected strains recovered from patients with bacteremia or meningitis. Three groups of pneumococci were tested: penicillin-susceptible strains, strains with intermediate penicillin resistance, and penicillin-resistant strains. Minimal inhibitory concentrations of benzyl penicillin, oxacillin, cephalothin, cefamandole, cefoxitin, moxalactam (LY127935), cefotaxime (HR756), piperacillin, pirbenicillin, N-formimidoyl thienamycin (MK0787), cefoperazone (T1551), mezlocillin, azlocillin, and mecillinam were determined. For all groups of pneumococci tested, cefotaxime, and particularly thienamycin, had the greatest activity. Piperacillin, mezlocillin, and azlocillin had activity similar to that of benzyl penicillin. Cefoperazone had less activity than penicillin against strains with penicillin minimal inhibitory concentrations of less than 1 microgram/ml but greater activity than penicillin against strains with greater resistance. Oxacillin, cephalothin, cefamandole, and pirbenicillin all had less activity for each group of pneumococci tested; moxalactam, cefoxitin, and mecillinam had the least activity. The relative differences in susceptibility to penicillin of each group of pneumococci tested were similar for each of the beta-lactam agents tested. The clinical effectiveness of cefotaxime and thienamycin for therapy of disease due to penicillin-resistant pneumococci needs further evaluation, and of particular interest will be the levels of these drugs which can be achieved in cerebrospinal fluid.

Cephalosporins↗
PubMed1981

Cephalosporins.

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Administration, Oral↗
PubMed1981

Vancomycin therapy in patients with impaired renal function: a nomogram for dosage.

The relation between vancomycin clearance and renal function was studied in 22 patients with various degrees of renal functional impairment and in four normal volunteers. Clearance of vancomycin and creatinine were highly correlated (r = 0.92) among 17 persons not on dialysis. In five dialysis patients vancomycin clearance averaged 0.086 mL/min . kg of body weight (+/- SEM = 0.025). These relations enabled us to construct a nomogram for vancomycin dosage adjustment (based on a mean steady-state serum vancomycin concentration of 15 micrograms/mL) in patients with various degrees of renal functional impairment.

Adolescent↗
PubMed1981

Essential characteristics of antibiotics for the treatment of seriously ill patients.

To realize their full potential for effective therapy in critically ill patients, antimicrobial agents must share three essential characteristics, namely in vivo as well as in vitro effectiveness, lack of toxicity, and reasonable cost. In vitro activity depends on the ability of the antimicrobial agent to reach its microbial target site and to overcome various mechanisms of resistance in the infecting organism. Although there is a general correlation between in vitro effectiveness and in vivo utility, this is not always true. In addition to having in vitro activity against the infecting organism, effective drugs must penetrate to the site of infection and must retain significant activity at that location. Antimicrobial agents ideally should be nontoxic at all dose levels and should not be metabolized to toxic intermediates. Direct toxicity (adverse effects) is often relatively easy to assess, but antimicrobial agents may also produce subtle abnormalities in host defense mechanisms that are more difficult to assess. In addition to the market price of a given antimicrobial agent, one must also consider the cost of monitoring for the treatment of adverse effects.

Animals↗
PubMed1980

Single-dose kinetics of intravenous vancomycin.

The pharmacokinetic properties of intravenously administered vancomycin were studied in four healthy volunteers. Reversible adverse effects (flushing, tachycardia, pruritus) occurred in two subjects who received high-dose rapid intravenous infusions. Distribution of vancomycin proceeded as a biphasic process in all four subjects. The initial distribution half-life (t1/2 alpha) was less than 8 minutes in all cases, with intermediate half-lives (t1/2 pi) varying from 0.43 to 1.48 hour and elimination half-lives (t1/2 beta) varying from 4.7 to 11.2 hours. Vancomycin clearance was less than creatinine clearance, probably because of serum protein binding, which was determined to be 55 per cent.

Adult↗
PubMed1980

Hemophilus influenzae in hospitalized adults: current perspectives.

In an eight year period 16 cases of serious extrapulmonary Hemophilus influenzae infection in adults were identified, including cases of meningitis, pericarditis, epiglottitis, empyema, cellulitis, osteomyelitis, endometritis, urinary tract infection, orbital cellulitis, primary peritonitis, mesenteric lymphadenitis and aortic graft infection. An 18 month prospective study of H. influenzae infection in hospitalized adults identified 10 cases of bronchitis, 25 of pneumonia and 65 of respiratory tract colonization, but there were no extrapulmonary infections. In 29 percent of the respiratory tract infections, H. influenzae appeared to be a nosocomial pathogen; in 71 percent, the infection was mixed. Finally, 110 clinical isolates of H. influenzae were studied for antimicrobial susceptibility. Eight percent were ampicillin resistant, two strains were resistant to tetracycline and one to chloramphenicol, but all were susceptible to trimethoprim-sulfamethoxazole and cefamandole.

Adolescent↗
PubMed1980

Diphtheroid prosthetic valve endocarditis. A study of clinical features and infecting organisms.

The clinical features of 19 patients with prosthetic valve endocarditis due to diphtheroids were studied. Infection was noted within 60 days of cardiac surgery in 12 (63 percent) patients. Prosthetic dysfunction and infection of the valve annulus was common (74 percent). Agar dilution minimal inhibitory concentrations for 18 diphtheroids isolated from patients with prosthetic valve endocarditis indicated that 88 percent were susceptible to gentamicin, amikacin, streptomycin, erythromycin and tetracycline; all strains were susceptible to vancomycin. In time-kill studies vancomycin was highly bactericidal as was gentamicin for susceptible strains. For gentamicin-susceptible strains, penicillin-gentamicin combinations were synergistic regardless of the susceptibility of the strains to penicillin. Bactericidal synergy of penicillin-gentamicin combinations was not seen with gentamicin-resistant strains. The biochemical and physiologic features of 20 strains were studied; with the exception of colonial morphology, 18 strains were found to be similar. Four strains were classified as belonging to the group JK by the Center for Disease Control (CDC) and 14 other strains fulfilled CDC criteria for group JK diphtheroids. A technique and criteria for single disc diffusion susceptibility testing are suggested.

Anti-Bacterial Agents↗