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Biomedical subjects

K E Aldridge

Publications and source records attributed to K E Aldridge.

At least 19 recordsLinked to original sources
PubMed1992

Vancomycin-enriched corneal storage medium.

Antibiotics in a corneal preservation solution probably have little effect during storage at 4 C, but are effective as the tissue is warmed. The tissue acts as a sponge, soaking up the antibiotic from the solution and releasing it into the eye, where the bactericidal effect is achieved. Currently, high concentrations of gentamicin (relative to the minimal inhibitory concentration) are used in the preserving solution for this purpose. Presumably, proportionately high concentrations of any proposed new antibiotic added to supplement the bactericidal effect of gentamicin, such as the vancomycin used in this study, would be required. However, neither the ability of donor tissue to tolerate high concentrations of vancomycin nor the stability of vancomycin at neutral pH in appropriate storage media has been documented. We evaluated the addition of vancomycin (100 micrograms/ml) to two corneal storage media that contained gentamicin in terms of stability of the antibiotic in solution and the effect on the endothelial cells of donor tissue stored for two weeks at 4 C. Vancomycin was stable in solution at neutral pH (7.2) during the five-month period of the study; the concentration exceeded 90 micrograms/ml for the first five weeks. The endothelial cells from donor tissue stored in the vancomycin-enriched media showed no notable differences from those stored in the same media without vancomycin in terms of cell shape, cell borders, cell swelling, and apical holes. The stability of vancomycin in storage and the absence of endothelial toxicity in vitro support the potential use of this antibiotic as a supplement to gentamicin for the prevention of endophthalmitis in patients receiving corneal transplants.

Aged↗
PubMed1992

Current antimicrobial therapy of anaerobic infections.

The treatment of many anaerobic infections involves antimicrobial therapy, appropriate surgical drainage of abscesses, and debridement of devitalized tissue. Most anaerobic infections are polymicrobial and require treatment with agents active against an array of aerobic and anaerobic bacteria. Bacterial resistance, especially to penicillins and tetracyclines, but also to newer agents of other classes, continues to increase. As a result, treatment with more than one drug is often required. Combination therapy is often necessary in serious infection, and is indicated for empiric treatment before receiving culture results. In the past combination therapy has been the mainstay of antimicrobial therapy, but more recent studies suggest that monotherapy for anaerobic infections may dominate the future. Selection of an agent requires consideration of the site of infection and the most likely etiologic agents. In vitro susceptibility is important, but it is not the only determinant of antimicrobial effectiveness. The pharmacology of the drug--absorption, distribution, concentrations in body fluids and tissues, excretion and metabolism--also plays an important role. The nature and severity of the underlying illness are important factors in selecting empiric therapy. Although it is a clinical judgement, in patients considered to have mild to moderate infections, several factors in selecting antimicrobial agents may be considered, including cost, whereas in patients judged to have severe or life-threatening infections, the most potent agents should be chosen as initial therapy, regardless of cost. Finally, the toxicities of the agent must also be considered.

Anti-Bacterial Agents↗
PubMed1992

In vitro activity of various antimicrobial agents against Staphylococcus aureus isolates including fluoroquinolone- and oxacillin-resistant strains.

To determine susceptibility to 31 old and new antimicrobials, 44 strains of Staphylococcus aureus, most resistant to oxacillin and ciprofloxacin and isolated in a community hospital, were tested in vitro. For the peptide/peptide-derivative compounds, with the exception of mersacidin, all strains were inhibited by less than or equal to 2 micrograms/ml. Minimum inhibitory concentration (MIC)90 values indicated mupirocin, teicoplanin, and MDL 62211 to be fourfold more active than vancomycin, ramoplanin, and decaplanin. For fluoroquinolones, ciprofloxacin-resistant S. aureus exhibited high-level cross-resistance to ofloxacin, norfloxacin, fleroxacin, enoxacin, and Ro 23-9424. WIN 57253, a new fluorinated naphthyridine, showed good activity against these strains. Among the beta-lactams, the penem-derivative compounds (imipenem, meropenem, FCE 22101, and HRE 664) had the greatest activity, although resistance to each compound was detected among oxacillin-resistant S. aureus. The presence of tazobactam reduced the piperacillin MIC90 fourfold. Oxacillin-susceptible strains were susceptible to cephalosporins/cephamycins, whereas most oxacillin-resistant strains exhibited resistance. This study has shown that certain old and new quinolones and peptide-derivative compounds have good in vitro activity against multiply resistant strains of S. aureus.

Aminoglycosides↗
PubMed1992

In vitro antistaphylococcal activities of two investigative fluoroquinolones, CI-960 and WIN 57273, compared with those of ciprofloxacin, mupirocin (pseudomonic acid), and peptide-class antimicrobial agents.

By using broth microdilution, 373 clinical isolates of staphylococci were studied to determine their susceptibilities to CI-960, WIN 57273, ciprofloxacin, mupirocin, vancomycin, teicoplanin, and ramoplanin. Test strains comprised 179 strains of Staphylococcus aureus and 194 strains of coagulase-negative species. Strains of S. aureus were susceptible to CI-960, which had a mode MIC of 0.032 micrograms/ml and an MIC for 90% of the strains of 2 micrograms/ml. CI-960 was equally active against methicillin-susceptible and -resistant S. aureus strains as well as ciprofloxacin-resistant strains. Similarly, WIN 57273 was highly active, with a mode MIC of 0.008 micrograms/ml and an MIC for 90% of the strains of 1 micrograms/ml. No cross-resistance to CI-960 and WIN 57273 among ciprofloxacin-resistant strains was detected. Mupirocin was four- to eightfold more active than ramoplanin, vancomycin, and teicoplanin. With regard to coagulase-negative staphylococci, CI-960 and WIN 57273 were the most active of the test compounds, inhibiting all strains at 0.5 and 1 micrograms/ml, respectively. Against the same strains, mupirocin was fourfold more active than ramoplanin and eightfold more active than vancomycin. Five strains of S. haemolyticus were found to be resistant to ciprofloxacin, while resistance to teicoplanin was found among strains of S. epidermidis, S. haemolyticus, S. hominis, S. saprophyticus, S. simulans, S. warneri, and S. xylosus.

Anti-Infective Agents↗
PubMed1992

In vitro antistaphylococcal activity and testing of RP 59500, a new streptogramin, by two methods.

The in vitro antistaphylococcal activity of RP 59500, a new streptogramin, was comparable to those of vancomycin and teicoplanin against Staphylococcus aureus, and RP 59500 was the most active agent against coagulase-negative staphylococci. All staphylococcal strains were inhibited by 4 micrograms of RP 59500 per ml, including multiply resistant strains. Broth microdilution and agar dilution testing gave comparable results in 97% of the tests with RP 59500.

Humans↗
PubMed1991

Bactericidal activity of ceftizoxime, cefotetan, and clindamycin against cefoxitin-resistant strains of the Bacteroides fragilis group.

The bactericidal activity of ceftizoxime, cefotetan, and clindamycin at 0.5 x MIC, 1 x MIC, and 4 x MIC was determined by killing kinetic studies for 12 cefoxitin-resistant strains of the Bacteroides fragilis group. Ceftizoxime and clindamycin had greater bactericidal activity than cefotetan. The degree of bactericidal activity of each compound increased as the concentration increased from subinhibitory (0.5 x MIC) to suprainhibitory concentrations (4 x MIC). Comparison of the bactericidal activity at the MIC of the test agents with the MIC showed greater killing of susceptible strains than the resistant strains. Interestingly, ceftizoxime was more active than clindamycin, or cefotetan, against strains with high cefoxitin MIC values.

Bacteroides fragilis↗
PubMed1991

Role of newer antimicrobial agents in the treatment of mixed aerobic and anaerobic infections.

Mixed infections with aerobic and anaerobic bacteria are being recognized with increasing frequency in clinical practice. Several concepts regarding such infections are clinically significant for the physician. These include the presence and significance of species in the Bacteroides fragilis group at clinical sites of infection, the facilitation of B. fragilis virulence by beta-lactamase producing aerobic bacteria and the role of enterococci in such infections. In response to the need for new forms of therapy for mixed aerobic and anaerobic infections, several new classes of antimicrobial agents have been introduced. Some of these allow for the potential option of monotherapy in certain clinical settings. In addition to clinical and microbiologic efficacy, safety and cost-effectiveness are factors that must be addressed with regard to these agents.

Anti-Bacterial Agents↗
PubMed1991

Antimicrobial therapy of anaerobic infections, 1991.

Most anaerobic infections are polymicrobial and must be treated with agents active against a variety of both aerobic and anaerobic bacteria. Antimicrobial therapy is used both to contain infections and to treat those that have not been contained (bacteremia). Bacterial resistance, especially to penicillins and tetracyclines, but also to newer agents of other classes, continues to increase and often requires treatment with more than one drug. Combination therapy is also frequently necessary in serious infections, and is indicated for empiric management before receiving results of in vitro microbiology laboratory tests. However, recent results suggest that monotherapy for anaerobic infections may dominate in the future, although combination therapy has been the mainstay of antimicrobial therapy. Selection of an agent must take into account the site of infection and thus the bacteria most likely to be found. It should be kept in mind that in vitro susceptibility is not the only determinant of antimicrobial effectiveness. The pharmacology of the drug--absorption, distribution, concentration in body fluids and tissues, and metabolism--also plays an important role. Finally, the nature and severity of the underlying illness, the toxicity of the agent, and costs must be considered.

Anti-Bacterial Agents↗
PubMed1990

In-vitro study of the susceptibility of cefoxitin/cefotetan resistant Bacteroides fragilis group strains to various other antimicrobial agents.

The in-vitro activity of various beta-lactam antibiotics, beta-lactam/beta-lactamase inhibitor combinations, clindamycin, and metronidazole was determined against Bacteroides fragilis group isolates that were resistant to both cefoxitin and cefotetan. Among the cephalosporins tested ceftizoxime was the most active with 80% of the strains susceptible, followed by cefotaxime (65% susceptible), and cefoperazone (47% susceptible). Piperacillin and clindamycin showed comparable activity to ceftizoxime with 80% and 81% susceptible, respectively. The addition of a beta-lactamase inhibitor (sulbactam, clavulanate, or tazobactam) enhanced the activity of the various beta-lactam agents from 4-fold to 16-fold overall. One strain of B. fragilis was found that was resistant to all beta-lactam agents either alone or in combination. All strains in this study were susceptible to less than or equal to 4 mg/l of metronidazole.

Aminoglycosides↗
PubMed1990

Comparison of in vitro antibiograms of Bacteroides fragilis group isolates: differences in resistance rates in two institutions because of differences in susceptibility testing methodology.

With 120 clinical isolates of the Bacteroides fragilis group, a comparison of rates of resistance to selected antimicrobial agents by using two susceptibility tests was performed in two medical institutions. The broth microdilution method produced MICs significantly lower than those determined by the agar dilution method. With ceftizoxime and cefoxitin, 88 and 18%, respectively, of the MICs were greater than or equal to 2 twofold dilutions apart. These differences in MIC results produced major interpretive discrepancies for ceftizoxime and cefoxitin, whereas no significant differences in resistance rates were noted for clindamycin and metronidazole.

Anti-Bacterial Agents↗
PubMed1990

Discordant results between the broth disk elution and broth microdilution susceptibility tests with Bacteroides fragilis group isolates.

Susceptibility testing of 161 clinical isolates of the Bacteroides fragilis group was performed to compare interpretive results generated by the broth disk elution and broth microdilution methods recommended by the National Committee for Clinical Laboratory Standards. Among the cephalosporin-cephamycin compounds tested, correlation was poorest for ceftizoxime (71%), ceftriaxone (57%), and cefotaxime (47%); when the tests did not correlate, false resistance was seen 92, 95, and 93% of the time, respectively. Cefotetan and cefoperazone showed lack of correlation in 19 and 20% of the tests, respectively. For cefotetan, false resistance was more frequent, while with cefoperazone, false susceptibility occurred more often. Cefoxitin produced the fewest discrepancies; 10% of the disk elution tests produced either false-resistance or false-susceptibility results. Mezlocillin and piperacillin showed lack of correlation in 8 and 14% of the tests, respectively, and discrepancies were due primarily to false-resistance results. Overall with the beta-lactams, 84% of the discordant interpretive results were false resistance by the broth disk elution test. Clindamycin had a discrepancy rate of 10%, with the majority of discrepancies being false susceptibility disk elution results. Because of the high number of discrepancies noted with ceftizoxime, ceftriaxone, and cefotaxime, we recommend that these drugs not be tested by the disk elution method and that they be tested by a quantitative MIC method such as the broth microdilution test. Furthermore, caution should be exercised when interpreting broth disk elution results with all the beta-lactams included in this study except imipenem. These data indicate the lack of correlation of results between these two tests for many beta-lactams and suggest the need for a reexamination of the disk elution method to provide a more accurately standardized test.

Bacteroides fragilis↗
PubMed1990

An update on the in vitro activity of ceftizoxime and other cephalosporin/cephamycin antimicrobial agents against clinically significant anaerobic bacteria.

The in vitro activity of certain beta-lactam agents against aerobic and anaerobic bacteria is influenced by the method and medium used for susceptibility testing. The in vitro activity of ceftizoxime and cefoxitin against Bacteroides fragilis group strains varies when either the broth microdilution or agar dilution method is used. In general, minimal inhibitory concentration values from broth microdilution are two- to fourfold lower than those from agar dilution. Broth microdilution test results with ceftizoxime have recently been shown to correlate more closely with clinical outcome in patients than those from agar dilution testing. Broth microdilution has become the recommended method of the National Committee for Clinical Laboratory Standards for testing ceftizoxime. Using broth microdilution testing, the in vitro activity of ceftizoxime has been shown to be as good as or better than that of cefoxitin, cefotetan, and cefotaxime against anaerobes, including the B fragilis group. Ceftizoxime also had good activity against B fragilis group strains resistant to cefoxitin or cefotetan. Time-kill kinetic studies have shown that the bactericidal activity of ceftizoxime is equal to or greater than that of cefoxitin or cefotetan against both cefoxitin-susceptible or cefoxitin-resistant strains of the B fragilis group.

Bacteria, Anaerobic↗
PubMed1990

In vitro anaerobic data on ticarcillin/clavulanate. A review of an ongoing survey.

Although a number of new antimicrobial agents described as "broad spectrum" have been introduced during the past several years, it should be recognized that each of them has its own unique spectrum of activity, strengths and weaknesses that define its appropriate clinical use. This report reviews the comparative susceptibility data on 495 bacterial isolates obtained from obstetric and gynecologic patients and on 522 Bacteroides fragilis group isolates. Susceptibility testing was conducted with broth microdilution using twofold dilutions of antimicrobials. The overall minimal inhibitory concentrations-90 (MIC90) for the 495 isolates were very low, and few resistant isolates were found. The MIC90 for cefotetan was 16 times greater than that for ticarcillin/clavulanate and ampicillin/sulbactam. Cephalosporins showed good activity against anaerobic cocci but variable activity against anaerobic gram-negative rods. A relatively high percentage of B fragilis group isolates were also resistant to clindamycin. The addition of 2 mg/mL of clavulanate to ticarcillin caused a 4- to 32-fold decrease in the MIC90 for various Bacteroides species. Less than 2% of the strains tested were resistant to clavulanate plus ticarcillin or amoxicillin. These results suggest that monotherapy with such agents could replace combination antibiotic therapy for mixed obstetric and gynecologic infections.

Ampicillin↗
PubMed1989

Fusobacterium necrophorum sepsis with cerebral infarction.

We have described the case of a 23-month-old female child in whom Fusobacterium sepsis progressed to cerebral infarction despite therapy with intravenous chloramphenicol and ampicillin. Some clinical improvement was noted upon addition of metronidazole to the treatment regimen. The child survived, but has severe neurologic sequelae. Physicians should suspect anaerobic infection in children who have signs of severe neurologic infection and in whom cultures are negative for aerobes. In selected cases, early treatment with metronidazole may be helpful.

Cerebral Infarction↗
PubMed1989

Multicenter in vitro evaluation of SM-7338, a new carbapenem.

A new carbapenem, SM-7338, was compared with imipenem, cefotaxime, and ceftazidime at five medical centers. Nearly 6,000 strains were tested by reference methods of the National Committee for Clinical Laboratory Standards, and SM-7338 inhibited the largest percentage of gram-negative bacilli. Its spectrum included all members of the family Enterobacteriaceae (99.7% were susceptible to less than or equal to 4 micrograms/ml), Pseudomonas spp. (but not Xanthomonas maltophilia), and Acinetobacter spp. The potency and spectrum of SM-7338 against the gram-positive organisms were less than those of imipenem and superior to those of ceftazidime. Only the enterococci and some oxacillin-resistant staphylococci were less susceptible to SM-7338 (MICs for 90% of isolates, greater than or equal to 8 micrograms/ml). Organisms resistant to ceftazidime were generally susceptible to SM-7338 and imipenem (76%). However, for one-third of the imipenem-resistant gram-negative bacilli (MICs, greater than 8 micrograms/ml), SM-7338 MICs were less than or equal to 4 micrograms/ml. Some endemic differences in patterns of SM-7338 activity against selected gram-negative species were found among some medical centers.

Anti-Bacterial Agents↗
PubMed1988

Multicenter in vitro evaluation of lomefloxacin (NY-198, SC-47111), including tests against nearly 7,000 bacterial isolates and preliminary recommendations for susceptibility testing.

Lomefloxacin (NY-198 or SC-47111) is a difluoro-quinolone derivative having a C-methyl at the 3-position of the piperazine ring, thus minimizing its metabolic alteration in vivo. In our research, its antimicrobial activity was most similar to that of difloxacin, enoxacin, fleroxacin, and norfloxacin but usually less than that of ciprofloxacin and ofloxacin against most species. Lomefloxacin shared cross-resistance with other 4-quinolones but remained very active against ceftazidime-resistant organisms, including stably derepressed beta-lactamase producing Gram-negative bacilli. Lower pH increased the lomefloxacin MICs. MBCs were usually identical to the measured MIC, and the lomefloxacin MICs were not significantly increased by high inoculum concentrations. The Enterobacteriaceae were found to have a very low rate of spontaneous mutation to lomefloxacin resistance (10(-8)-10(-9). In vitro tests by 5-micrograms and 10-micrograms lomefloxacin disks and dilution methods were correlated, and the 10-micrograms disk was recommended for clinical trials using a less than or equal to 4 micrograms/ml susceptible breakpoint. The quality assurance guidelines for dilution tests were determined by a multilaboratory study.

4-Quinolones↗
PubMed1987

RO23-6240, a new orally absorbed quinolone: in vitro comparison with other broad-spectrum oral antimicrobial agents and imipenem.

A total of 626 clinical isolates were tested for their susceptibility to RO23-6240 and other broad-spectrum antimicrobial agents. RO23-6240 showed good activity against strains of Enterobacteriaceae, Acinetobacter, and P. aeruginosa. RO23-6240 MIC90s ranged from 0.032 to 4 micrograms/ml for these strains. RO23-6240 also showed good activity against staphylococci, both methicillin-susceptible and -resistant strains. The activity in vitro of RO23-6240 was comparable with that of norfloxacin and ofloxacin, and more active than imipenem, trimethoprim-sulfamethoxazole, cefaclor, and amoxycillin/clavulanate potassium. As with the other quinolones tested, increases in inoculum size produced moderate increases in the MICs and MBCs of RO23-6240.

Anti-Bacterial Agents↗