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Biomedical subjects

R C Moellering

Publications and source records attributed to R C Moellering.

At least 181 records · Page 10Linked to original sources
PubMed1978

Penicillin-netilmicin synergism against Streptococcus faecalis.

The combination of penicillin plus netilmicin was synergistic in vitro against 28 strains of Streptococcus faecalis and compared favorably with penicillin in combination with gentamicin. Similarly, penicillin plus netilmicin was as effective as penicillin plus gentamicin in the therapy of 67 rabbits with enterococcal endocarditis produced with a streptomycin-susceptible (S) or a streptomycin-resistant (R) strain of S. faecalis. After 5 days of infection, control rabbits had bacterial titers of 10(10) colony-forming units (CFU)/g of vegetation. Those treated with penicillin plus netilmicin had mean titers of 10(5.2) and 10(5.1) CFU/g for S and R strains, respectively, and those treated with penicillin plus gentamicin had mean valve titers of 10(5.8) CFU/g for both strains. After 10 days of therapy, mean valve titers with penicillin plus netilmicin were 10(3.8) and 10(4.7) CFU/g, and with penicillin plus gentamicin they were 10(4.5) and 10(5.4) CFU/g for S and R strains, respectively. Thus, if netilmicin proves to be less toxic than other aminoglycoside antibiotics, it may have potential usefulness in the therapy of enterococcal endocarditis.

Animals↗
PubMed1978

Antimicrobial susceptibility of flavobacteria.

Antimicrobial susceptibility patterns of 28 clinical isolates of Flavobacterium sp. were determined by standard disk diffusion technique and by antimicrobial dilution in agar. Rifampin, clindamycin, trimethoprim-sulfamethoxazole, cefoxitin, and vancomycin are among the antimicrobial agents which may be clinically useful to treat infections caused by flavobacteria. All 28 isolates were resistant to erythromycin with minimal inhibitory concentrations of 32 mug/ml or more. Currently recommended interpretive zones of inhibition by disk diffusion did not reliably predict antimicrobial susceptibility of the 28 flavobacteria isolates when compared with the agar dilution technique, and, therefore, a more direct measurement of minimal inhibitory or bactericidal concentration is recommended.

Anti-Bacterial Agents↗
PubMed1978

Plasmid-mediated resistance to antibiotic synergism in enterococci.

Mating experiments have shown that high-level resistance (minimal inhibitory concentration greater than 2,000 microgram/ml) to streptomycin and kanamycin, and resistance to penicillin-streptomycin and penicillin-kanamycin synergism are transferable by conjugation from resistant clinical isolates of enterococci to a sensitive recipient strain. Cesium chloride-ethidium bromide ultracentrifugation revealed a satellite (plasmid) band in resistant clinical isolates and the transconjugant strains but not in the sensitive recipient. Examination of these satellite bands by agarose gel electrophoresis and electron microscopy demonstrated a common plasmid with a weight of 45 megadaltons. Novobiocin treatment of a resistant clinical isolate produced simultaneous loss of high-level resistance to streptomycin and kanamycin, and of resistance to penicillin-aminoglycoside synergism. These results suggest that (a) high-level resistance to streptomycin and kanamycin among some clinical isolates of enterococci is associated with a 45 megadalton plasmid, and (b) the same plasmid is also responsible for the resistance to penicillin-aminoglycoside synergism observed in these strains.

Aminoglycosides↗
PubMed1978

Aminoglycoside-inactivating enzymes in clinical isolates of Streptococcus faecalis. An explanation for resistance to antibiotic synergism.

Clinical isolates of enterococci (Streptococcus faecalis) with high-level resistance to both streptomycin and kanamycin (minimal inhibitory concentration >2,000 mug/ml), and resistant to synergism with penicillin and streptomycin or kanamycin were examined for aminoglycoside-inactivating enzymes. All of the 10 strains studied had streptomycin adenylyltransferase and neomycin phosphotransferase activities; the latter enzyme phosphorylated amikacin as well as its normal substrates, such as kanamycin. Substrate profiles of the neomycin phosphotransferase activity suggested that phosphorylation occurred at the 3'-hydroxyl position, i.e., aminoglycoside 3'-phosphotransferase. A transconjugant strain, which acquired high-level aminoglycoside resistance and resistance to antibiotic synergism after mating with a resistant clinical isolate, also acquired both enzyme activities. Quantitative phosphorylation of amikacin in vitro by a sonicate of the transconjugant strain inactivated the antibiotic, as measured by bioassay, and the phosphorylated drug failed to produce synergism when combined with penicillin against a strain sensitive to penicillin-amikacin synergism.No differences were found in the sensitivity of ribosomes from a sensitive and resistant strain when examined in vitro using polyuridylic acid directed [(14)C]-phenylalanine incorporation in the presence of streptomycin, kanamycin, or amikacin. Therefore, we conclude that aminoglycoside-inactivating enzymes are responsible for the aminoglycoside resistance, and resistance to antibiotic synergism observed in these strains.

Aminoglycosides↗
PubMed1977

Resistance to gentamicin, tobramycin and amikacin among clinical isolates of bacteria.

Susceptibility to the administration of gentamicin, tobramycin and amikacin was determined for all isolates of aerobic and facultative gram-negative bacilli submitted for testing to the clinical bacteriology laboratory of the Massachusetts General Hospital between July 1, 1974, and June 30, 1976. In this 24-month period more than 46,000 isolates of bacteria were tested by the single-disc diffusion (Bauer-Kirby) method. Resistance to one or more of the aforementioned aminoglycosidic aminocyclitol antibiotics was found among 4,114 stains. Correlation with quantitative susceptibility test methods revealed that disc-diffusion methods using 10 microng discs accurately predicted resistance to gentamicin and tobramycin, but overestimated the prevalence of resistance to amikacin by 20 to 60%. Most of the gentamicin-resistant Enterobacteriaceae in this study were also cross-resistant to tobramycin but were susceptible to amikacin. Many gentamicin-resistant strains of Ps. aeruginosa were susceptible to both tobramycin and amikacin. Resistance to amikacin tended to be of relatively low magnitude (most had minimal inhibitory concentrations (MIC's) between 31 and 125 microng/ml), but organisms which were resistant to the administration of amikacin were usually resistant to the other two aminoglycosidic antibiotics as well.

Amikacin↗
PubMed1977

Infections with Acinetobacter calcoaceticus (Herellea vaginicola): clinical and laboratory studies.

In a retrospective review of 53 patients, 58 episodes of infection due to Acinetobacter calcoaceticus var. anitratus (Herellea vaginicola) were studied. Although the organism is widely distributed in nature, it is of relatively low virulence since colonization is more frequently noted than infection and since most infections occur in patients subjected to the epidemiologic pressures common to nosocomial, gram-negative bacillary infection: prior antibiotic therapy; instrumentation and manipulation (e.g., endotracheal intubation, urinary bladder catheterization, arterial and venous cannulation); surgery; hospitalization, especially with residence in an intensive care unit; severe underlying disease, either systemic (e.g., chronic obstructive pulmonary disease, malignancy) or localized to the infected area (e.g., prior bacterial or aspirational pneumonia, trauma). Pneumonia was the most common infection due to A. calcoaceticus, and occurred only in patients with a tracheostomy or endotracheal tube in place. In over half the 25 patients, more than one lobe was involved and bronchopneumonia was the usual roentgenographic appearance. Cavitation (2 patients) and empyema formation (3 patients) were uncommon. The severity of acinetobacter pneumonia is reflected in the high mortality rate (44% overall, with a 36% mortality rate due primarily to infection). Tracheobronchitis due to A. calcoaceticus was less severe than pneumonia since no patients died primarily as a result of the infection. Urinary tract infections occurred in five patients, none of whom were ill and none of whom died. Urinary bladder catheterization was thought to be responsible for infection in three patients, and in at least four of the five patients infection was restricted to the lower tract. Wound infections were noted in six patients who had undergone surgery and were related to the presence of foreign bodies in the operative site in five of the patients. Surgical debridement and/or drainage of the infected area was the primary therapeutic measure employed in most cases. Only one patient died and this was a result of noninfectious causes. Skin infection due to A. calcoaceticus was seen in two patients, one of whom exhibited fulminant, fatal cellulitis and septicemia in the setting of pancytopenia. All nine patients with acinetobacter septicemia had received antecedent antibiotic therapy, and in all cases intravenous catheters were in place at the time bacteremia occurred. Clinically, seven of the nine patients were in shock. The mortality rate was 44% overall, with a 22% mortality rate due to infection. Although septicemia was thought to be "line-related" in five of the nine patients, serious post-bacteremic complications developed in three patients: prosthetic valve endocarditis, suppurative thrombophlebitis and subhepatic abscess.

Acinetobacter↗
PubMed1977

In vitro synergism between carbenicillin and aminoglycosidic aminocyclitols against Acinetobacter calcoaceticus var. anitratus.

Acinetobacter caleoaceticus var. anitratus is a nonfermentative, gram-negative bacillus that has been demonstrated to cause severe infections, usually in hospitalized patients. Since mild to moderate resistance of A. calcoaceticus to one or more aminoglycosidic aminocyclitols has been noted to occur, a study was undertaken to evaluate the activity of combinations of carbenicillin with either kanamycin, tobramycin, or gentamicin against 28 isolates of A. calcoaceticus obtained from clinical sources. Synergism (defined as at least 100-fold-increased killing at 24 h by the combination as compared with the most efficacious of the individual antibiotics) was demonstrated against 26 of 28 strains of A. calcoaceticus with carbenicillin plus kanamycin and carbenicillin plus tobramycin and against 25 of 28 strains with carbenicillin plus gentamicin. The median increased killing for the 28 strains was 4.2 log(10) with carbenicillin plus kanamycin and with carbenicillin plus tobramycin and 3.1 log(10) with carbenicillin plus gentamicin. The most important determinant of synergistic potential of each combination was the level of resistance of each strain of A. calcoaceticus to the aminoglycoside component of the combination.

Acinetobacter↗
PubMed1977

Resistance to six aminoglycosidic aminocyclitol antibiotics among enterococci: prevalence, evolution, and relationship to synergism with penicillin.

Two hundred and three recent clinical isolates of enterococci were tested for susceptibility to streptomycin, kanamycin, amikacin, gentamicin, sisomicin, and tobramycin. Depending upon the source of the isolate, 36 to 54% of the enterococci demonstrated high-level resistance (minimal inhibitory concentration, >2,000 mug/ml) to streptomycin, 16 to 49% to kanamycin, and 0 to 14% to amikacin. None of the strains was highly resistant to gentamicin, sisomicin, or tobramycin. A comparison with isolates of enterococci obtained in 1968 revealed that there has been a decrease in prevalence of high-level resistance among organisms isolated from wound cultures in 1976. However, no decrease in resistance to streptomycin or kanamycin was demonstrated among blood or urine isolates. Penicillin, combined with gentamicin, sisomicin, or tobramycin, was synergistic against all 10 strains of Streptococcus faecalis subjected to formal testing. For streptomycin and kanamycin, the presence or absence of synergism with penicillin correlated with the absence or presence of high-level aminoglycoside resistance. High-level resistance to amikacin was seen in only 1 of the 10 strains. Nonetheless, combinations of penicillin plus amikacin failed to produce synergistic killing against 6 of the 10 strains. Indeed, the combination was synergistic only against those four strains that were susceptible to high levels of kanamycin.

Aminoglycosides↗
PubMed1977

Cephalothin prophylaxis in cardiac valve surgery. A prospective, double-blind comparison of two-day and six-day regimens.

A prospective, double-blind study comparing a 6 day with a 2 day regimen of cephalothin prophylaxis was conducted among 200 patients undergoing prosthetic valve replacement. No cases of endocarditis occurred during the 2 month follow-up. Sternal wound infection developed in 2.8 per cent of the 6 day group and 2.1 per cent of the 2 day group. Pneumonia developed in 8.5 per cent of the 6 day and 5.3 per cent of the 2 day group; most of the bacteria isolated were susceptible to cephalothin. Urinary tract infection developed more frequently in the 2 day group (17.0 versus 8.5 per cent), particularly during the first 6 postoperative days. Three of 11 patients with no detectable cephalothin in their sera at the close of operation developed staphylococcal wound infections, compared with 2 of 175 patients whose sera contained cephalothin at the close of surgery (p = 0.002, Fisher's exact test). A short course of prophylactic antibiotics is prudent, but there is no justification for prolonging their administration.

Cephalothin↗
PubMed1977

Microbiologic basis for the rational use of prophylactic antibiotics.

Appropriate use of antibiotics is enhanced by the effective application of data on antimicrobial susceptibility. A number of methods are currently available for routine determination of susceptibilities, including agar dilution, broth dilution, agar diffusion, and several semiautomated methods. If susceptibility testing is properly done, it can serve as the basis for the generation of statistical data of use to the clinician. Periodically updated tables detailing the antimicrobial susceptibilities of commonly isolated organisms enable the physician to make appropriate choices of antibiotics for prophylaxis and for the initial treatment of serious infections, before the susceptibilities of the infecting organisms are known. With computer assistance, it is possible to use susceptibility data for quality control and for more sophisticated epidemiologic purposes. For the past several years, we have studied a number of potential uses of computer-generated data at the Massachusetts General Hospital. Several of these applications, especially as they might relate to the prophylactic use of antibiotics, are discussed in this paper.

Anaerobiosis↗
PubMed1976

Bacteremic infections due to clindamycin-resistant streptococci.

We have recently observed four patients with bacteremic infections due to group A streptococci that were highly resistant to clindamycin and only moderately susceptible to erythromycin. Two of the infections developed while the patients were receiving clindamycin. The organisms were not beta-hemolytic under standard conditions nor were they M or T typable. We urge that all streptococci isolated from patients with serious infections be grouped serologically and be tested for antibiotic susceptibilities, especially if therapy with antibiotics other than penicillin is to be considered.

Aged↗