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Biomedical subjects

W J Holloway

Publications and source records attributed to W J Holloway.

At least 19 recordsLinked to original sources

Minimal inhibitory concentrations and minimal bactericidal concentrations of quinupristin/dalfopristin against clinical isolates of Corynebacterium jeikeium and Listeria monocytogenes.

Thirty clinical isolates of Listeria monocytogenes and 30 clinical isolates of Corynebacterium jeikeium were tested against quinupristin/dalfopristin by the NCCLS broth macrodilution technique for determination of MICs. MBC testing was also performed on the 60 isolates. Quinupristin/dalfopristin MIC90 values against L. monocytogenes and C. jeikeium were 1.6 mg/L and 0.2 mg/L, respectively. Quinupristin/dalfopristin was bacteriostatic against these organisms.

Anti-Bacterial Agents

Clinical applications of a new parenteral antibiotic in the treatment of severe bacterial infections.

Cephalosporins are one of the mainstays of antibiotic therapy, and third-generation cephalosporins are first-line agents for the treatment of many types of serious infections, including those of nosocomial origin. Gaps in activity of currently available third-generation cephalosporins such as cefotaxime, cefoperazone, ceftriaxone, and ceftazidime, and increasing reports of gram-negative bacilli resistance to some of these agents, especially Klebsiella pneumoniae, Pseudomonas aeruginosa, and Enterobacter spp., make it necessary to investigate new compounds. Cefepime, a fourth-generation cephalosporin with a wide range of activity against gram-positive and gram-negative bacteria, including multi-resistant strains of Enterobacteriaceae, was evaluated in comparison with ceftazidime for the treatment of serious infections in hospitalized patients. Ceftazidime is a commonly prescribed third-generation cephalosporin used for empiric treatment of serious infections such as pneumonia, urinary tract infection, and skin and skin-structure infection. This investigation was an open, randomized comparative study involving 882 patients in North America. Cefepime 2 g every 12 hours demonstrated similar efficacy to that of ceftazidime 2 g every 8 hours for the treatment of pneumonia and urinary tract infection (including cases associated with concurrent bacteremia), and skin and skin-structure infections. The bacteriologic responses were generally >85%. The most common pathogens isolated were Escherichia coll, Streptococcus pneumoniae, P. aeruginosa, K. pneumoniae, Haemophilus influenzae, Staphylococcus aureus, and Streptococcus, group B. Overall, approximately 94% of pathogens isolated in pretreatment cultures were susceptible to cefepime and ceftazidime. Cefepime and ceftazidime were well tolerated; only 3% of patients in each group discontinued therapy because of an adverse event. The most common adverse events were headache, diarrhea, nausea, vomiting, pruritus, and rash. The results of this study indicate that cefepime is a promising, effective, and safe single-agent therapy for serious infections in hospitalized patients.

Acute Disease

In vitro activity of LY333328, an investigational glycopeptide antibiotic, against enterococci and staphylococci.

The in vitro activities of LY333328 were compared with those of vancomycin, teicoplanin, and quinupristin-dalfopristin (Synercid) against 219 strains of enterococci and staphylococci, including vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus. MICs and MBCs were determined by a microtiter dilution protocol. LY333328 demonstrated superior activity against vancomycin-resistant enterococci and was the only antibiotic which was bactericidal. Its potency was comparable or superior to those of other antibiotics tested against methicillin-resistant staphylococci.

Anti-Bacterial Agents

A multicenter comparative study of meropenem and imipenem/cilastatin in the treatment of complicated urinary tract infections in hospitalized patients.

The safety and efficacy of meropenem and imipenem/cilastatin were compared in the treatment of hospitalized patients with complicated urinary tract infections (UTIs) in a prospective, multicenter, open, parallel-group trial. Patients were randomized to receive 500-mg intravenous doses of either meropenem every 8 hours (n = 116) or imipenem/cilastatin every 6 hours (n = 119). Data from 95 patients given meropenem and 82 patients given imipenem/cilastatin were included in the evaluation of efficacy. Meropenem produced satisfactory clinical and bacteriologic responses in 99% and 90% of cases, respectively. These results were similar to those obtained with imipenem/cilastatin, which produced clinical improvement in 99% of cases and bacteriologic improvement in 81%. Two patients given meropenem and five patients given imipenem/cilastatin developed superinfections. The rate of relapse was similar in the two groups. Patients who received meropenem had fewer drug-related adverse reactions than did recipients of imipenem/cilastatin (8% vs. 19%). The results of this study demonstrate that meropenem is a safe and effective alternative to imipenem/cilastatin in the treatment of hospitalized patients with complicated UTIs.

Bacteria

In vitro synergy studies with Clostridium difficile.

Agar dilution anaerobic susceptibility studies using rifampin, vancomycin, metronidazole, and bacitracin individually and in combination were performed with Clostridium difficile. Fifty-five strains of C. difficile were studied. Eighty-five percent of strains tested (29 of 34) were synergistically inhibited by the combination of bacitracin and rifampin (fractional inhibitory concentration, less than or equal to 0.50).

Bacitracin

Cefmetazole treatment of intra-abdominal infection.

Seventy-nine patients were enrolled in a study comparing cefmetazole and cefoxitin as single agent antibiotic therapy for intra-abdominal infection. Thirty-seven patients had appendicitis, 16 patients had perforated peptic ulcer while 26 patients had a variety of other infectious processes. The clinical response to both antibiotics was good and tolerance was equivalent. Four patients with Pseudomonas aeruginosa isolated from the initial culture experienced microbiological failure. Three patients treated with cefmetazole had prolongation of the prothrombin time.

Abdomen

Infection in women. Clinical experience with beta-lactamase inhibitors.

Because of the high incidence of beta-lactamase production among bacteria that are found commonly in pelvic infections in women, beta-lactamase-inhibiting antibiotics should prove effective in treating those infections. In a randomized, comparative study of 47 women with intraabdominal infections, 23 received ticarcillin disodium/clavulanate potassium, and 24 received cefoxitin. Among the infections treated were endometritis, pelvic inflammatory disease, amnionitis, salpingitis, septicemia, intraabdominal abscess and pelvic abscess. The bacteriologic response to ticarcillin disodium/clavulanate potassium was 88.8% success as compared with 87.5% for cefoxitin. Clinical cures were achieved in 98.8% of patients treated with ticarcillin disodium/clavulanate potassium and 90.9% of patients treated with cefoxitin. The adverse reactions were diarrhea, transient eosinophilia and transient thrombocytosis.

Adult

Management of sepsis in the elderly.

Mortality due to serious infections is significantly higher among elderly patients than among younger patients. This differential is particularly striking in some subsets of patients; for example, the mortality rate among older patients with afebrile bacteremia is 65 percent, compared with 25 to 35 percent in younger patients. Although serious underlying disease is an important reason for older patients' difficulties with infection, other problems of these patients include a tendency to deny the presence of disease and some obstacles to interaction with the health care system. Older patients with infection are less likely to present with typical symptoms, which makes early recognition difficult for physicians. For example, typical findings of sepsis (mental obtundation, tachycardia, and fever) may be absent in an elderly patient; the only clue may be the patient's failure to eat. Once sepsis is recognized, its source must be identified. Urinary tract infection is the most common cause of sepsis in the elderly and responds best to antibiotic therapy. Pneumonia is the next most common cause and leads to the highest mortality in this age group; rapid (sometimes invasive) methods must be utilized to identify the etiologic agent. In this life-threatening infection, initial antibiotic therapy should include an aminoglycoside, such as amikacin, to ensure the broadest coverage against the common pathogens. Supportive measures should be instituted for patients with sepsis, including careful monitoring of fluid intake and output and special attention to adequate oxygenation. Fluid volume replacement must be carried out in patients with septic shock, and hemodynamic monitoring with a Swan-Ganz catheter should be performed frequently. Careful consideration should be given to the use of corticosteroids and inotropic agents. After appropriate cultures have been obtained, antibiotics should be started; the time from initial presentation to the administration of the first dose of antibiotic should not exceed one hour. Important considerations in antibiotic selection include the patient's history and environment (community, nursing home, or hospital), anatomic location of the infection, and the pathogen. In our institution, initial empiric antibiotic therapy consists of a combination of amikacin and cefotaxime. When older patients are treated, adjustments in dosing should be based on estimates of kidney function.

Aged

Infectious disease emergencies.

Patient visits to the primary care physician are prompted most often by an infectious disease. The clinician must be aware of the common and serious infections present in the community and must institute proper diagnostic and therapeutic measures. Diagnosis and treatment of streptococcal infections, staphylococcal infections, pneumonia and upper respiratory tract infection, bone and joint infections, sinusitis, clostridial infections, and tetanus are discussed.

Anti-Bacterial Agents

Treatment of infections in hospitalized patients with ticarcillin plus clavulanic acid. A comparative study.

Ninety patients at the Wilmington Medical Center were enrolled in a comparative study to evaluate the efficacy and toxicity of ticarcillin plus clavulanic acid in the treatment of a variety of infections. Forty-seven women with obstetric or gynecologic infections were randomly assigned to receive ticarcillin plus clavulanic acid or cefoxitin. Forty-three patients with gram-negative septicemia or lower respiratory tract infection were given ticarcillin plus clavulanic acid or tobramycin plus piperacillin in a randomized fashion. Of the 47 women with obstetric or gynecologic infections, 23 were randomly assigned to receive ticarcillin plus clavulanic acid, and 24 were randomly assigned to receive cefoxitin. Several patients in each group had underlying diseases such as diabetes, obesity, and hypertension. Of the 27 pathogens isolated in the group receiving ticarcillin plus clavulanic acid, 26 (96 percent) were eradicated, including all three ticarcillin-resistant pathogens. In the cefoxitin-treated group, 31 of the 33 (94 percent) pathogens were eliminated, including all four ticarcillin-resistant organisms. Three reinfections or superinfections occurred, and cefoxitin therapy failed to eliminate an enterococcus isolate from the endometrium in one patient. The clinical response in both treatment groups was excellent. Either cure or clinical improvement was achieved for all 18 sites of infection in the ticarcillin plus clavulanic acid-treated group and for all 22 sites in the cefoxitin-treated group. There were no systemic drug reactions in either treatment group. In one patient in the cefoxitin-treated group, local phlebitis developed at the infusion site. This reaction responded to local therapy. There were no local reactions among the patients receiving ticarcillin plus clavulanic acid. Of the 43 patients with gram-negative septicemia or lower respiratory tract infection, 21 were randomly assigned to receive ticarcillin plus clavulanic acid and 22 were assigned to receive tobramycin plus piperacillin. Thirty-six patients had gram-negative sepsis, and seven patients had lower respiratory tract infection. Nine of the 36 patients suspected of having gram-negative sepsis were not evaluable because no pathogen was isolated prior to treatment. Twenty-two of the 27 patients treated for septicemia had good clinical and microbiologic responses. Three of the seven patients with pneumonia were not evaluable. Of the four evaluable patients, two had pneumococcus pneumonia; one was treated with tobramycin plus piperacillin and one with ticarcillin plus clavulanic acid. In both instances, the clinical and bacteriologic responses were considered good.

Adolescent

Serratia marcescens pyarthrosis and osteomyelitis.

We have reported a case of Serratia marcescens arthritis and osteomyelitis in a young man whose source of infection appeared to be a single episode of intravenous amphetamine use. Multiple antibiotics and aggressive surgical management were necessary to effect a cure. He eventually responded to a three-week course of amikacin and moxalactam given in conjunction with surgical debridement of all involved areas.

Adult

Spectinomycin.

Spectinomycin is a broad-spectrum aminocyclitol antibiotic that is highly effective in the treatment of uncomplicated gonorrhea. It is the drug of choice for the treatment of gonorrhea that fails to respond to other therapy and is a good alternative drug in the treatment of penicillin-allergic patients. Spectinomycin should be considered the drug of choice in the treatment of gonorrhea in areas where penicillinase-producing strains of Neisseria gonorrhoeae are prevalent. Spectinomycin is not predictably effective in the treatment of oral pharyngeal gonorrhea but may be used in penicillin-allergic patients with disseminated gonorrhea. While spectinomycin has some activity against other human pathogens, it is unlikely that this agent will be found useful in infections other than those due to Neisseria gonorrhoeae.

Bacteria