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Biomedical subjects

M F Parry

Publications and source records attributed to M F Parry.

At least 19 recordsLinked to original sources

Aztreonam susceptibility testing. A retrospective analysis.

Aztreonam is a structurally and immunologically unique beta-lactam antibiotic with activity exclusively against aerobic gram-negative micro-organisms. Between 1983 and 1988, its antimicrobial spectrum was evaluated against more than 5,800 fresh clinical isolates at a 300-bed community teaching hospital. Only 1.1 percent of Enterobacteriaceae isolates were resistant to aztreonam over the five-year study period, an incidence similar to that observed with aminoglycoside antibiotics. Aztreonam was found to be more active than third-generation cephalosporins and comparable with mezlocillin against Enterobacter spp., Morganella, and Citrobacter freundii. Although aztreonam was somewhat less active against nonfermenting gram-negative bacilli, such as Pseudomonas and Acinetobacter, overall more than 90 percent of Pseudomonas aeruginosa isolates were susceptible. Ceftazidime was the most active beta-lactam tested against nonfermenters. Against aerobic gram-positive cocci, aztreonam possessed no clinically useful activity. No significant change in susceptibility to aztreonam was observed over the five-year study period for Enterobacteriaceae. For third-generation cephalosporins, however, a trend toward increased resistance was noted, particularly for Enterobacter spp. and C. freundii. A 50 percent increase in resistance to aztreonam was observed over the five-year study period for nonfermenters, particularly P. aeruginosa and Acinetobacter anitratus. Similar increases in resistance were seen with other beta-lactams and gentamicin. Based on its potent in vitro activity, aztreonam appears to be a useful agent and a desirable alternative to aminoglycoside antibiotics for the treatment of pure aerobic gram-negative bacillary infections, or as a component in combination therapy against mixed infections.

Ampicillin

Quinolone resistance. Susceptibility data from a 300-bed community hospital.

Introduction of the fluoroquinolones has altered physician prescribing practices in the treatment of infectious diseases for both inpatients and outpatients. To evaluate the impact of unrestricted prescribing of these agents, the antimicrobial susceptibility of clinical isolates to ciprofloxacin and other commonly used antibiotics was prospectively studied in a 300-bed community teaching hospital. Only 0.6 percent (nine of 1,454 isolates) of fresh clinical isolates were resistant to ciprofloxacin (minimal inhibitory concentration value greater than 2 micrograms/ml) in an initial study conducted between 1984 and 1985. A similar pattern was observed in the second half of 1987 (0.5 percent, or five of 940 isolates), just prior to the release of ciprofloxacin. Throughout 1988, however, as quinolone usage rose, the incidence of ciprofloxacin resistance rose, reaching a peak of 4.0 percent in the last quarter of 1988. Of 63 ciprofloxacin-resistant isolates in 1988, 22 were Pseudomonas and 28 were staphylococci, representing resistance rates of 6.5 and 4.2 percent, respectively. Enterobacteriaceae remained exquisitely susceptible with only five of 1,720 isolates (0.3 percent) resistant to ciprofloxacin. Seventy-two percent of ciprofloxacin-resistant isolates were recovered from patients who had received a fluoroquinolone within the previous month. If these isolates are subtracted from the total number of resistant micro-organisms recovered, baseline fluoroquinolone resistance did not change significantly from 1984 to 1988. Soft-tissue infections (50 percent) represented the greatest source of ciprofloxacin-resistant organisms, including osteomyelitis, but urinary tract infections (26 percent), all associated with instrumentation, were also a significant source. Although the fluoroquinolones are extremely valuable antimicrobial agents, the emergence of drug resistance may be promoted when these drugs are used for treatment of chronic infections or when poorly drained abscesses, necrotic tissue, or indwelling foreign bodies are present.

Anti-Infective Agents

Epidemiology and mechanisms of antimicrobial resistance.

Bacterial evolution and the emergence of antimicrobial drug resistance continue to interfere with the successful treatment of infections by both community- and hospital-based physicians. Resistance has emerged to even the newer, most potent antimicrobial agents. Although generalizations can be made about the appropriateness of antimicrobial agents on the basis of published susceptibility patterns, significant regional, demographic, and interinstitutional variables exist that require each hospital to establish its own antibiotic data base and antibiogram. In particular, multiresistant pathogens occur infrequently in acute care community hospitals compared with tertiary care centers. Important clinical factors that promote the emergence of drug-resistant flora include prolonged therapy, the persistence of foreign bodies, sequestra, or prostheses, and the inadequate surgical debridement of necrotic tissue or abscesses. Antibiotic resistance may occur through changes in the permeability of the cell wall or outer membrane, by alteration of the antimicrobial binding or target site, and by inactivation or modification of the drug by bacterial enzymes. These mechanisms are reviewed. In particular, gram-negative beta-lactamases, methicillin-resistant staphylococci, multiresistant enterococci, and the emergence of fluoroquinolone resistance are discussed in detail.

Anti-Bacterial Agents

Epidemiologic factors affecting antimicrobial resistance of common bacterial isolates.

The pattern of antimicrobial resistance of common bacterial isolates obtained from various groups of patients at a large tertiary-care center was compared with the pattern of resistance seen at a primary-care community hospital. At the tertiary-care center, significant differences in susceptibility were seen between pediatric and adult groups. In the tertiary-care center, the inpatients were more likely than the outpatients to have resistant staphylococcal and enterobacterial strains. Comparison of the overall resistance at the tertiary-care center and the primary-care hospital showed that resistance to cephalosporins, piperacillin, and aminoglycosides was significantly higher at the tertiary-care hospital than at the community hospital. Striking differences were noted in the resistance of nosocomial Enterobacter and Citrobacter isolates. Hospitals should be cautious in extrapolating nationwide data to their particular institutions.

Adolescent

Oral ciprofloxacin therapy of infections due to Pseudomonas aeruginosa.

The efficacy and safety of oral ciprofloxacin, a fluoroquinolone, were evaluated in the treatment of infection due to Pseudomonas aeruginosa. 96 infections in 71 patients were treated. Substantial underlying disease was present in most of the patients, and 25 (35%) were seriously ill. 52% of pseudomonas isolates were carbenicillin-resistant, and 31% gentamicin-resistant. The overall clinical response rate was 77%-28 of 35 exacerbations of cystic fibrosis respiratory disease, 17 of 19 urinary infections, 4 of 6 osteomyelitis, and 11 of 15 soft tissue infections. The bacteriological cure rate was 34%-0 of 35 cystic fibrosis, 4 of 17 respiratory infections, 17 of 19 urinary infections, 4 of 6 osteomyelitis, and 8 of 15 soft tissue infections. Ps aeruginosa developed resistance to ciprofloxacin in 25 of 96 infections. Side-effects were generally slight with nausea in 14 (15%) the most common, and there were only two substantial superinfections.

Administration, Oral

Pseudomembranous colitis caused by topical clindamycin phosphate.

Pseudomembranous colitis was observed on two occasions in the same patient and was associated with the topical administration of clindamycin phosphate. Assay for Clostridium difficile toxin was positive, and the patient was ultimately cured by oral vancomycin hydrochloride and the withdrawal of clindamycin therapy.

Acne Vulgaris

The epidemiology of hepatitis B infection in housestaff.

Ninety-nine medical and surgical house officers were prospectively evaluated during internship and residency for the development of hepatitis B virus (HBV) infection. The overall incidence of hepatitis B was 10.2% per year. Eighty-six percent of episodes were subclinical. The greatest risk factor appeared to be frequent hand-to-mouth activity such as smoking or licking requisition labels. The presence of a hemodialysis or transplantation unit may be an additional institutional risk factor. HBV infection was not associated with a history of needle-sticks or contact with known antigen-positive patients. Educational efforts to minimize HBV infection should concentrate on handwashing techniques and discouragement of hand-to-mouth activity in patient care areas.

Habits

Therapy of serious infections with cefamandole.

Forty-four patients with serious bacterial infections were treated with cefamandole in a dose 1--2 g every four to six hours. Thirty-two patients were cured and six were markedly improved. Three of six failures were due to superinfection with cephalothin-resistant microorganisms. The over-all bacteriologic response was 80%. In 12 of 13 patients with bacteremia the blood was sterilized. Ten of 14 patients with gram-negative bacillary infections responded to treatment. Six of these were due to cephalothin-resistant microorganisms, three of which responded. Fifteen patients who were treated had a history of penicillin allergy. There were no serious reactions although skin rash did develop. Phlebitis was uncommon.

Adolescent

A comparative study of ticarcillin plus tobramycin versus carbenicillin plus gentamicin for the treatment of serious infections due to gram-negative bacilli.

The combination of ticarcillin plus tobramycin (TT) or carbenicillin plus gentamicin (CG) was used to treat 82 patients with severe systemic gram-negative infection in a prospective, randomized study. Pseudomonas aeruginosa was the primary pathogen in 7 (93 per cent) of these patients. Patients treated with TT responded more frequently (92 per cent or 37 of 40) than patients treated with CG (71 per cent or 30 of 42) (p is less than 0.05). This difference was primarily due to a greater response to TT in patients with pulmonary infections (93 per cent versus 68 per cent) and infections due to Pseudomonas (92 per cent versus 70 per cent). Severity of underlying disease was also an important determinant of response. Except for a greater incidence of hepatotoxicity with CG (23 per cent versus 3 per cent; p is less than 0.02), there was no difference in toxicity, colonization with drug-resistant microorganisms or superinfection between the two treatment groups. The combination of TT appears to be superior to CG for the treatment of pulmonary infections due to Pseudomonas aeruginosa.

Anti-Bacterial Agents

Acute interstitial nephritis associated with carbenicillin therapy.

Although acute interstitial nephritis has been documented during therapy with many antibiotics of the penicillin class, it has not previously been reported in association with carbenicillin therapy. We report here the case of a patient who developed the characteristic clinical features of this form of injury while receiving prolonged large doses of carbenicillin. Histologic examination confirmed the presence of a striking interstitial nephritis. Carbenicillin should be considered a potential cause of renal damage in patients who develop rash, eosinophilia, and microscopic hematuria in association with deterioration of renal function.

Acute Disease

Treatment of pulmonary infections in patients with cystic fibrosis: a comparative study of ticarcillin and gentamicin.

The effectiveness of ticarcillin against Pseudomonas aeruginosa in acute exacerbations of pulmonary infection in patients with cystic fibrosis was evaluated. Seventy-one percent of patients treated with ticarcillin alone responded favorably. The response rate was similar in patients treated with a combination of ticarcillin plus gentamicin or with gentamicin alone. Severity of the underlying disease was the most important determinant of response to treatment. Ticarcillin-resistant organisms were recovered during treatment in 50% of patients who received this drug; recovery of them was not prevented by the inclusion of gentamicin in the therapeutic regimen nor did they interfere with clinical improvement. The ticarcillin-resistant strains persisted at follow-up, two to six months after completion of therapy, in only one of ten patients. No serious toxicity to ticarcillin was noted during the study period.

Adolescent

Effect of N-acetylcysteine on antibiotic activity and bacterial growth in vitro.

The antibiotic bacerial inactivity of N-acetylcysteine (NAC) and its interaction with penicillin and aminocyclitol antibiotics was evaluated. NAC inhibited growth of both gram-negative and gram-positive bacteria. Strains of Pseudomonas aeruginosa were more susceptible than other microorgainsms tested. P. aeruginosa strains were inhibited synergistically by NAC and carbenicillin or ticarcillin. However, NAC antagonized the activity of gentamicin and tobramycin. These findings have implications for the combined clinical use of NAC and aerosolized antibiotics and are also important for the processing of sputum specimens in the microbiology laboratory.

Acetylcysteine

Pharmacokinetics of ticarcillin in patients with abnormal renal function.

The pharmacokinetics of ticarcillin were determined in patients with abnormal renal function. In individuals with rates of creatinine clearance of greater than 60 ml per min, the half-life (+/- standard deviation) of ticarcillin was 71 +/- 6 min after intravenous administration. In patients with rates of creatinine clearance of 30-60 ml per min, 10-30 ml per min, and less than 10 ml per min, ticarcillin had a half-life of 3.0 +/- 0.6 hr, 8.5 +/- 2.1 hr, and 14.8 +/- 3.7 hr, respectively. Urinary concentrations of ticarcillin after intravenous administration were adequate at all levels of renal function. Ticarcillin was removed by hemodialysis with a reduction in half-life to 3.4 +/- 0.8 hr, but peritoneal dialysis was minimally effective in removing the drug. A program for the use of ticarcillin patients with renal insufficiency was outlined.

Clinical Trials as Topic

Tobramycin and ticarcillin therapy for exacerbations of pulmonary disease in patients with cystic fibrosis.

Patients who had cystic fibrosis and acute infectious exacerbations of pulmonary disease produced by Pseudomonas aeruginosa were treated with a combination of tobramycin and ticarcillin. P. aeruginosa recovered from patients was inhibited by lower concentrations of both of these drugs than of gentamicin or carbenicillin. Thirteen courses of treatment were administered to 11 patients (mean, 14.4 days). A favorable response was seen in 11 of 12 completed courses of treatment. Improvement was associated with decreases in white blood cell count, temperature, and sedimentation rate. Adverse reactions were uncommon. Although P. aeruginosa was not eradicated from the sputum, the clinical results suggest that the combination of tobramycin and ticarcillin may be particularly useful for treatment of acute exacerbations of pulmonary disease in patients with cystic fibrosis from whom P. aeruginosa is isolated.

Adolescent