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Biomedical subjects

C W Stratton

Publications and source records attributed to C W Stratton.

At least 19 recordsLinked to original sources
PubMed1997

Avoiding fluoroquinolone resistance. Strategies for primary care practice.

The therapeutic usefulness of fluroquinolones for serious and difficult-to-treat infections is well documented. However, with increasing reports of organisms becoming resistant to the agents (most often the pseudomonads, staphylococci, and streptococci), the usefulness of this class of antibiotics is being threatened. Appropriate and judicious prescribing of this class of antimicrobials can greatly aid in preserving the therapeutic value of fluoroquinolones for the treatment of infections in the future.

Anti-Bacterial Agents↗
PubMed1996

Lactobacillus bacteremia: description of the clinical course in adult patients without endocarditis.

Lactobacillus bacteremia in the absence of endocarditis is a rare entity, and the clinical relevance of such bacteremia remains unclear. The clinical courses of lactobacillus bacteremia without endocarditis in 43 previously described patients and 12 new patients were reviewed. Bacteremia with Lactobacillus alone occurred in 34 (62%) of the patients, and 12 (22%) of the patients had bacteremia with other organisms, including Lactobacillus. Lactobacillus was isolated from another site in 18 (33%) of these patients. Intravenous catheter infections were not noted in these patients. Underlying conditions included cancer (6 patients), organ transplantation (9), diabetes mellitus (4), and recent surgery (12). Fever occurred in all patients, and eight (15%) of the patients experienced a sepsis syndrome. The mortality rate was 14%; however, only three deaths were attributed soley to lactobacillus sepsis. Lactobacillus bacteremia is an uncommon condition that usually occurs in patients with severe underlying illnesses and is frequently seen as a part of a polymicrobial infection. Blood cultures positive for Lactobacillus represent true infection and not contamination. Although resistance to commonly used antibiotics is common, the mortality rate associated with this bacteremia appears to be low.

Adult↗
PubMed1996

Effective treatment of multidrug-resistant enterococcal experimental endocarditis with combinations of cell wall-active agents.

The efficacy of treatment with a combination of ampicillin, imipenem, and vancomycin was compared with that of two-drug combinations or monotherapy in a model of experimental endocarditis using a strain of Enterococcus faecium with high-level resistance to vancomycin and moderate intrinsic resistance to ampicillin and imipenem. In vitro time-kill synergy studies demonstrated bactericidal synergistic activity only for the triple combination. In vivo, monotherapy with vancomycin was not effective. Treatment with either ampicillin or imipenem alone or in combination with vancomycin resulted in <4 log10 reduction in colony-forming units (cfu) per gram of vegetation. The combination of ampicillin with imipenem was highly active (an additional 5 log10 reduction in cfu per gram of vegetation compared with the most active single agent), but efficacy was not increased by the addition of vancomycin to ampicillin and imipenem. Therapy with the combination of ampicillin and imipenem may be effective for some strains of multidrug-resistant enterococcal infections.

Ampicillin↗
PubMed1995

Diminished activity of ceftizoxime in comparison to cefotaxime and ceftriaxone against Streptococcus pneumoniae.

Previous reports documenting the essentially identical spectra of activity of ceftizoxime, cefotaxime, and ceftriaxone prompted our hospital formulary committee to replace the latter two drugs with ceftizoxime on the basis of cost differences. However, we subsequently observed that every one of 60 isolates of Streptococcus pneumoniae tested was less susceptible to ceftizoxime than to either cefotaxime or ceftriaxone. The difference between minimal inhibitory concentrations (MICs) was greatest for strains moderately or fully resistant to penicillin, which at our institution represent approximately 32% of all isolates of S. pneumoniae. Ten isolates with cefotaxime and ceftriaxone MICs of 2.0-6.0 micrograms/mL had ceftizoxime MICs of > or = 256 micrograms/mL. Time-kill kinetic studies assessing bactericidal activity confirmed the diminished activity of ceftizoxime against penicillin-resistant isolates of S. pneumoniae. Ceftizoxime should not be used to treat proven or suspected pneumococcal infection in areas where resistance to penicillin is prevalent.

Ceftizoxime↗
PubMed1995

Utilization of time-kill kinetic methodologies for assessing the bactericidal activities of ampicillin and bismuth, alone and in combination, against Helicobacter pylori in stationary and logarithmic growth phases.

Assessment of in vitro susceptibility testing of Helicobacter pylori is difficult because of the fastidious, slowly growing nature of this microorganism. The high rate of relapse observed clinically and a possible subpopulation of cells that are not actively replicating suggest the potential need for bactericidal therapy in order to eradicate H. pylori. We used modified time-kill kinetic methodology in order to evaluate the bactericidal activities of ampicillin and bismuth, alone and in combination, against three strains of H. pylori in both a stationary (slow) growth phase and a logarithmic (rapid) growth phase. We found that ampicillin produced a decrease in CFU per milliliter (2 to 4 log10 units) for three strains of H. pylori when tested in logarithmic growth phases but was less inhibitory (< 1-log10-unit decrease in CFU per milliliter) when tested in a stationary growth phase. In contrast, bismuth, when tested in a logarithmic growth phase, produced little inhibitory effect, as the CFU for all strains tested increased above the inoculum. However, when tested in a stationary growth phase, bismuth produced a decrease in CFU per milliliter of < 1 to > 3 log10 units). The activities of these two agents when combined mimicked the activity of the most active drug alone for that growth phase. We conclude that the clinical use of ampicillin combined with bismuth has been more effective than that of either agent used alone because ampicillin targets replicating cells, whereas bismuth targets cells that are not actively replicating.

Ampicillin↗
PubMed1995

Use of time-kill methodology to assess antimicrobial combinations against metronidazole-susceptible and metronidazole-resistant strains of Helicobacter pylori.

Optimal therapy for Helicobacter pylori infection to date, consists of metronidazole, bismuth, and tetracycline. This combination, however, is less effective against metronidazole-resistant organisms. We used a time-kill kinetic methodology to assess the bactericidal effects of selected agents, alone and in combination, to a metronidazole-susceptible and a metronidazole-resistant strain of H. pylori. single, double, and triple agents showed increasing bactericidal activity. The combination of metronidazole, bismuth, and tetracycline showed maximal killing effect (no detectable regrowth) against the susceptible strain, but against the resistant strain this combination showed less killing. The time-kill methodology may therefore offer an in vitro approach to the initial selection of agents to be evaluated for the treatment of H. pylori infections.

Anti-Bacterial Agents↗
PubMed1995

In vitro pharmacodynamics of piperacillin, piperacillin-tazobactam, and ciprofloxacin alone and in combination against Staphylococcus aureus, Klebsiella pneumoniae, Enterobacter cloacae, and Pseudomonas aeruginosa.

The time-kill curve methodology was used to determine the pharmacodynamics of piperacillin, ciprofloxacin, piperacillin-tazobactam and the combinations piperacillin-ciprofloxacin and ciprofloxacin-piperacillin-tazobactam. Kill curve studies were performed for piperacillin, ciprofloxacin, and piperacillin-tazobactam at concentrations of 0.25 to 50 times the MICs for 13 strains of bacteria: four Pseudomonas aeruginosa, three Enterobacter cloacae, three Klebsiella pneumoniae, and three Staphylococcus aureus isolates (tazobactam concentrations of 0.5, 4, and 12 micrograms/ml). By using a sigmoid Emax model and nonlinear least squares regression, the 50% lethal concentrations and the maximum lethal rates of each agent were determined for each bacterial strain. For piperacillin-ciprofloxacin and ciprofloxacin-piperacillin-tazobactam, kill curve studies were performed with concentrations obtained by the fractional maximal effect method (R. C. Li, J. J. Schentag, and D. E. Nix, Antimicrob. Agents Chemother. 37:523-531, 1993) and from individual 50% lethal concentrations and maximum lethal rates. Ciprofloxacin-piperacillin-tazobactam was evaluated only against the four P. aeruginosa strains. Interactions between piperacillin and ciprofloxacin were generally additive. At physiologically relevant concentrations of piperacillin and ciprofloxacin, ciprofloxacin had the highest rates of killing against K. pneumoniae. Piperacillin-tazobactam (12 micrograms/ml) had the highest rate of killing against E. cloacae. Piperacillin-ciprofloxacin with relatively higher ciprofloxacin concentrations had the greatest killing rates against S. aureus. This combination had significantly higher killing rates than piperacillin (P < 0.002). For all the bacterial strains tested, killing rates by ciprofloxacin were significantly higher than those by piperacillin-tazobactam (4 and 12 micrograms/ml had significantly higher killing rates than piperacillin alone (P < 0.02 and P < 0.004, respectively). The effect of the combination of piperacillin-ciprofloxacin, in which piperacillin concentrations were relatively higher, was not statistically different from that of piperacillin alone (p > or = 0.71). The combination of ciprofloxacin-piperacillin-tazobactam achieved greater killing than other combinations or monotherapies against P. aeruginosa. The reduction in the initial inoculum was 1 to 4 logs greater with ciprofloxacin-piperacillin-tazobactam at 4 and 12 micrograms/ml than with any other agent or combination of agents. On the basis of the additive effects prevalently demonstrated in the in vitro study, the combinations of piperacillin-ciprofloxacin and piperacillin-tazobactam are rational therapeutic options. Greater killing of P. aeruginosa was demonstrated with ciprofloxacin-piperacillin--tazobactam. Since treatment failure of P. aeruginosa pneumonia is a significant problem, clinical studies are warranted.

Anti-Infective Agents↗
PubMed1995

Factors affecting growth and susceptibility testing of Helicobacter pylori in liquid media.

In order to increase the database for in vitro growth and/or susceptibility testing in liquid media, we evaluated the growth of Helicobacter pylori in broth media containing 5% sheep blood. We also compared the effect of bismuth on the growth of H. pylori in broth media containing 10% fetal calf serum with the effect on growth in media containing 0.5% starch. In contrast to the result seen with agar, we found that sheep blood, whether whole or laked, inhibited the growth of H. pylori in broth media. In addition, we found that bismuth inhibited growth in media with starch but that this inhibition was negated in media with serum.

Agar↗
PubMed1994

Assessment of the bactericidal activity of sparfloxacin, ofloxacin, levofloxacin, and other fluoroquinolones compared with selected agents of proven efficacy against Listeria monocytogenes.

The search for alternative therapeutic agents for listeriosis includes the quinolone group. Accordingly, the bactericidal activity of ciprofloxacin, levofloxacin, lomefloxacin, ofloxacin, sparfloxacin, and temofloxacin, in comparison with that of ampicillin and sulfamethoxazole-trimethoprim, was evaluated against Listeria monocytogenes at 24 and 48 h of incubation using time-kill kinetic methodology. The inhibitory concentrations for each agent fell into a narrow range comparable with ampicillin. For example, the minimum inhibitory concentration (MIC) ranges, MIC90 (24 h), and MIC90 (48 h) of the most active quinolone, sparfloxacin, were 0.25-2, 2, and 2 micrograms/ml, respectively, with 4 micrograms/ml achieving > or = 99.9% killing of the inoculum at 24 h with no regrowth by 48 h. At 2-4 times the MIC, bactericidal activity for all quinolones tested was noted at 24 h, unlike the action of ampicillin, which only becomes bactericidal at 48 h. These concentrations are within the achievable range of serum concentrations for a number of these agents. Because selected new fluoroquinolones at two to four times the MIC show bactericidal activity at 24 h, these agents may prove useful as therapeutic alternatives for the treatment of listeriosis.

Ampicillin↗
PubMed1994

Production of A and C variants of staphylococcal beta-lactamase by methicillin-resistant strains of Staphylococcus aureus.

Most methicillin-resistant Staphylococcus aureus (MRSA) strains produce beta-lactamase. To determine whether this enzyme(s) is identical to one or more of the four beta-lactamases produced by methicillin-susceptible strains, the beta-lactamases of 50 MRSA isolates were typed by using substrate profile analysis. Forty type A, no type B, ten type C, and no type D beta-lactamase-producing strains were identified. The beta-lactamase inhibitor sulbactam reduced the MICs of beta-lactamase-labile antibiotics, including ampicillin, penicillin G, and cefazolin, for type A and type C MRSA strains.

Anti-Bacterial Agents↗
PubMed1994

Blood cultures and immunocompromised patients.

The diagnosis of blood-borne infections in immunocompromised patients is a major challenge for the clinical microbiology laboratory. Isolation of blood-borne pathogens in these patients has profound clinical implications, yet is fraught with technical problems. Contamination of blood cultures by skin flora is particularly problematic in the immunosuppressed host as these low-virulence microorganisms can be the cause of infection. Careful skin preparation is necessary to minimize such contamination. Drawing at least two blood samples for culture improves the specificity of this test on an individual patient. If possible, blood for culture should not be obtained through indwelling vascular devices. The microbiology laboratory must be aware of the wide range of blood-borne pathogens in immunocompromised patients and have available suitable techniques for the isolation of prevalent microorganisms. For most hospitals, this now must include techniques for the isolation of mycobacteria. Newer blood culture techniques have made the isolation of unusual pathogens easier. These techniques include the use of fluorescent stains, special media, antigen assays, and DNA probes. Each laboratory must evaluate current techniques in terms of suitability for use in its individual setting. Each must also be aware of new technologic developments. When clinical infection is suspected despite negative blood cultures, staff in the microbiology laboratory should be aware of special blood culture techniques or adjunctive procedures such as bone marrow and liver biopsies. These techniques may assist the clinician in making a diagnosis. Due to the practical limitations of blood culture technology as well as to economic constraints, the microbiology laboratory cannot routinely offer blood cultures suitable for the isolation of all blood-borne pathogens. Therefore, the microbiology laboratory must act in consultation with the clinician to determine the optimal approach for blood cultures in the immunocompromised patient. Such a consultative role with special blood culture techniques made available for selected types of immunosuppressed hosts allows the cost-effective use of the latest technology.

Bacteremia↗
PubMed1993

Tuberculosis, infection control, and the microbiology laboratory.

The diagnosis of tuberculosis is an increasingly important problem confronting the clinical microbiology laboratory as well as hospital epidemiologists. The inherent delays in conventional laboratory procedures for the isolation and susceptibility testing of M tuberculosis may contribute directly to the spread of tuberculosis. Application of newer methods that are more rapid is essential if the spread of tuberculosis is to be limited. Hospital epidemiologists and clinical microbiology laboratories should work together to critically examine all of their current procedures for tuberculosis and take steps to correct or improve all omissions and delays in mycobacterial tests ordering, collection, testing, and reporting.

Culture Media↗
PubMed1993

Clarithromycin as monotherapy for eradication of Helicobacter pylori: a randomized, double-blind trial.

UNLABELLED: Current regimens to eradicate Helicobacter pylori usually consist of metronidazole plus a bismuth compound, as well as a third agent such as tetracycline. Such regimens are not ideal because organisms may be metronidazole-resistant, side-effects occur, and compliance is often poor. This randomized, double-blind study was designed to assess the ability of clarithromycin, a new macrolide antimicrobial, as monotherapy to eradicate H. pylori. Thirty-seven healthy volunteers who were H. pylori positive by 13C-urea breath test plus histology and/or culture completed 14 days of oral therapy with clarithromycin in one of three dosages. Eradication, defined as all three tests negative at 4-6 wk after the end of therapy, was achieved in 2/13 (15%) with clarithromycin 500 mg bid, 4/11 (36%) with 1000 mg bid, and 7/13 (54%) with 500 mg qid. Isolates of H. pylori were resistant to clarithromycin prior to therapy in 12% of subjects, and became resistant during therapy in 21% of subjects. Taste perversion, the most common side effect, resulted in one subject terminating therapy. CONCLUSIONS: Whereas clarithromycin is a promising antimicrobial in the eradication of H. pylori, it is not sufficient to be used as monotherapy.

Adult↗
PubMed1993

Bactericidal testing.

Recognition of the importance of bactericidal activity in certain clinical settings has generated a great deal of interest in bactericidal testing. Indeed, bactericidal testing can be of great use in a number of settings, but it also has the potential for being overutilized. Moreover, there are biologic and technical pitfalls inherent in bactericidal testing. This article addresses these issues and summarizes the progress toward standardization of these methods. Thoughtful and deliberate application of standardized bactericidal testing should make this controversial test much more useful in the future.

Microbial Sensitivity Tests↗
PubMed1993

Focused microbiologic surveillance by specific hospital unit: practical application and clinical utility.

Focused microbiologic surveillance by specific hospital intensive care units (ICUs) revealed important differences in the occurrence of pathogens among units and at different times. Moreover, there were striking differences between the antibiogram summaries from certain ICUs and those from the hospital as a whole. Accordingly, an ongoing focused microbiologic surveillance was conducted for hospital ICUs to define unit-specific problems more clearly. To apply these data practically, results of focused surveillance were given to the ICU medical directors. The directors were able to institute unit-specific modifications of antimicrobial usage based upon the prevalent pathogens and their susceptibility patterns within each unit. After 1 year of this approach, the susceptibility patterns of Pseudomonas aeruginosa to imipenem and other antipseudomonal beta-lactam agents were improved in a number of ICUs that had previously noted resistance problems of several years' duration. Susceptibility of P aeruginosa was markedly improved in the medical ICU. The susceptibility patterns of Enterobacter cloacae were less affected, if at all. A review of antimicrobial use revealed that the use of most antipseudomonal agents in the medical ICU had decreased by approximately 50% or more. It is concluded that modification of antimicrobial use in ICUs based on focused microbiologic surveillance is a promising way to detect and minimize problems with resistance.

Drug Resistance, Microbial↗
PubMed1992

Blastomycosis in patients with the acquired immunodeficiency syndrome.

OBJECTIVE: To describe the clinical, demographic, radiographic, diagnostic, and therapeutic aspects of blastomycosis in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN: A retrospective survey. SETTING: Ten university medical centers and community hospitals, six in geographic areas endemic for Blastomyces dermatitidis, and four outside the endemic area. PATIENTS: We identified 15 patients with blastomycosis and positive serologic test results for human immunodeficiency virus (HIV). MEASUREMENTS: A diagnosis of blastomycosis was based on a positive culture (14 patients) or typical histopathologic features (one patient) for B. dermatitidis in clinical specimens. RESULTS: Twelve of 15 patients had a previous or concomitant AIDS-defining illness at the time of diagnosis of blastomycosis, and only one patient had a CD4 lymphocyte count of greater than 200 cells/mm3. Two patterns of disease emerged: localized pulmonary involvement (seven patients), and disseminated or extrapulmonary blastomycosis (eight patients). Central nervous system involvement was common (40%). Six patients died within 21 days of presentation with blastomycosis, including four patients with disseminated and two with fulminant pulmonary disease. Among the nine patients who survived longer than 1 month, all received amphotericin B as initial antifungal therapy, and most received subsequent therapy with ketoconazole. Only two of these nine patients died with evidence of progressive blastomycosis. CONCLUSIONS: Blastomycosis is a late and frequently fatal infectious complication in a few patients with AIDS. In these patients, overwhelming disseminated disease including involvement of the central nervous system is common, and it is associated with a high early mortality. Initial therapy with amphotericin B is appropriate in patients with AIDS and presumptive blastomycosis.

Acquired Immunodeficiency Syndrome↗