PubMed Health⌕ Search

Biomedical subjects

R L Marier

Publications and source records attributed to R L Marier.

33 records · Page 2Linked to original sources

Comparative clinical trial of imipenem-cilastatin (N-formimidoyl-thienamycin-dehydropeptidase inhibitor) and cefazolin.

One hundred and eighty-six patients were randomized to receive either imipenem-cilastatin (94 patients) or cefazolin (92 patients). Imipenem-cilastatin (250 mg 6 hourly iv) or cefazolin (1000 mg 6 hourly iv) were given for 5 to 14 days. An assessment of efficacy could be made in 141 patients, 72 of whom received imipenem-cilastatin and 69 of whom received cefazolin. Reasons for exclusion included failure to isolate a causative organism (20 patients), less than 5 days of treatment (16 patients), inadequate follow up or culture (5 patients), concomitant administration of another antibiotic (1 patient), and resistance to the study drug (3 patients, all of whom were in the cefazolin group). No isolates resistant to imipenem were found. Sites of infection included skin and soft tissue (91 patients), lower respiratory tract (21 patients), urinary tract (16 patients), bone and joint (8 patients), primary bacteraemia (4 patients) and miscellaneous other sites (1 patient). Bacteria isolated included Staphylococcus aureus (65 patients), group A streptococcus (42 patients), Escherichia coli (17 patients), other Gram-negative bacilli (37 patients), anaerobic bacteria (34 patients) and other bacteria. Imipenem was more active than cephalothin in vitro against pathogenic bacteria isolated from evaluable patients. Cure or improvement was seen in 68 of the 72 imipenem-cilastatin patients (94%) and in 68 of the 69 cefazolin patients (99%). Relatively few abnormal laboratory tests and adverse experiences were noted, and there were no differences in this between the two treatment groups. We concluded that imipenem-cilastatin is safe at the dose used. It is as effective as cefazolin in mild to moderate infections caused by common pathogens.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Susceptibility of anaerobic bacteria to beta-lactam antibiotics and beta-lactamase production.

We examined the susceptibility of various anaerobes to four beta-lactamase susceptible (ampicillin, amoxycillin, cyclacillin, and penicillin G) and two beta-lactamase resistant (moxalactam, and N-F-thienamycin) beta-lactam antibiotics and measured beta-lactamase production. Members of the Bacteroides groups were most resistant to the six antibiotics. N-F-thienamycin was the most effective antimicrobial agent against all the test strains, moxalactam the next most effective, and penicillin G the least. Beta-lactamase production was mainly confined to Bacteroides species. Cephalosporinase was the most common beta-lactamase produced; penicillinase was detected less often. About two thirds of the penicillin-resistant isolates produced cephalosporinase. N-F-thienamycin and moxalactam were the most active agents against those anaerobes that were resistant to many beta-lactam antibiotics.

Amoxicillin↗

Interlaboratory variation of antibiograms of methicillin-resistant and methicillin-susceptible Staphylococcus aureus strains with conventional and commercial testing systems.

Laboratory-prepared (conventional) and commercial susceptibility testing systems were compared by using a group of methicillin-resistant (MR) and methicillin-susceptible (MS) strains of Staphylococcus aureus. A group of 25 MR and 15 MS S. aureus strains were coded and tested blindly by disk diffusion, agar dilution, broth microdilution, Sensititre, Micro-Media, Sceptor, API 3600S, MicroScan, Autobac I, and MS-2 systems. All systems were incubated at 35 degrees C and read with either a manual or automated reader at the recommended times. Where applicable, systems were also read at 48 h. Among the conventional assays, the broth and agar dilution methods were comparable, both detecting 88% of the MR strains at 24 h and detecting 92 and 96%, respectively, at 48 h. The disk diffusion method was less efficient, detecting only 36 and 72% at 24 and 48 h, respectively. Detection of cephalothin resistance was low for all systems at both time periods, with agar dilution and disk diffusion being the most and least efficient, respectively. Some variability was also seen with detection of resistance to clindamycin and gentamicin. Among the MS strains, variability among the conventional systems occurred with methicillin, gentamicin, ampicillin, and penicillin. Comparison of the commercial systems with manual readers with the broth microdilution method (reference method) showed that for MR strains, the Sceptor system gave identical results at 24 and 48 h. Sensititre detected 68 and 88% of the MR strains, whereas Micro-Media was least effective detecting 12 and 80% at 24 and 48 h, respectively. None of the commercial systems detected cephalothin resistance well, with only one strain being indicated by the Sceptor and Sensititre systems at 48 h. Slight differences were also seen among the systems with clindamycin and gentamicin. With regard to the MS strains, variability among the systems was seen with methicillin, penicillin, ampicillin, clindamycin, and gentamicin. Among commercial systems with automated readers, the API system detected a greater number of MR strains than did the reference method at 24 and 48 h, 96 and 100%, respectively. The MicroScan method was comparable to the reference method detecting 80 and 88% of the MR strains at both time periods, respectively. Both Autobac I and MS-2 were much less effective in detecting MR strains, noting only 32 and 16%, respectively, at the 3- to 6-h readings. Poor detection of cephalothin resistance among MR strains was evident in all systems. Variability also occurred among the systems with clindamycin, gentamicin, and ampicillin. A single strain of the MR group was reported to be vancomycin resistant by the API system. Among the MS group, the greatest variability was seen with methicillin. Less variability occurred with penicillin, ampicillin, gentamicin, and vancomycin.

Humans↗

Treatment of systemic mycoses with ketoconazole: emphasis on toxicity and clinical response in 52 patients. National Institute of Allergy and Infectious Diseases collaborative antifungal study.

The pharmacology, in vitro mycologic activity, toxicity, and efficacy of ketoconazole were studied in a Phase-II evaluation by the National Institutes of Health and National Institute of Allergy and Infectious Disease Mycoses Study Group. This report emphasizes the toxicity and clinical response data in 52 patients with the following systemic mycoses: blastomycosis in 16 patients; nonmeningeal coccidioidomycosis in 13; histoplasmosis in 8; nonmeningeal cryptococcosis in 7; sporotrichosis in 7; and both blastomycosis and nonmeningeal coccidioidomycosis in 1. Maximum daily doses of ketoconazole were 100 mg in 1 patient; 200 mg in 23; 400 mg in 12; and 600 mg in 16. In 52% of the patients, duration of therapy ranged from less than 1 to 6 months, whereas in 35%, duration ranged from 7 to 12 months, and in 13%, from 12 to 22 months. In 35 patients (67%), evidence of toxicity was not seen. Nausea, anorexia, or vomiting occurred in 21%. Cure or marked improvement was shown in 27 patients (52%), whereas failure of the primary course was seen in 14 (27%) and relapse after ketoconazole was discontinued in 11 (21%). Although this evaluation did not provide clear-cut clinical response data, our results indicate that ketoconazole, in the dosage regimens used, was more effective in patients with histoplasmosis and nonmeningeal cryptococcosis than in patients with blastomycosis and nonmeningeal coccidioidomycosis, and least effective in patients with sporotrichosis.

Adolescent↗

Piperacillin v Carbenicillin in the therapy for serious infections.

One hundred seven patients were treated with either piperacillin (56) or carbenicillin (51) in an open randomized trial of hospitalized patients with pleuropulmonary (40), urinary tract (26), gynecologic (21), skin and soft-tissue (eight), joint (five), bone (three), and miscellaneous other infections (four). Patients with urinary tract infections were given 150 mg/kg/day of piperacillin sodium or 200 mg/kg/day or carbenicillin sodium in divided doses every six hours intravenously. Patients with other infections were given 250 mg/kg/day of piperacillin sodium and 450 mg/kg/day of carbenicillin sodium; 53/56 (95%) patients treated with piperacillin and 45/51 (88%) patients treated with carbenicillin were cured clinically. In general, the drugs were well tolerated. There were, however, more adverse experiences in the groups taking carbenicillin. Of special interest was the finding of liver function test abnormalities in 17/78 (21%) carbenicillin recipients (evaluative and nonevaluative cases). We concluded that piperacillin was effective and safe. It has potential for use in a great variety of infections.

Adult↗

N-formimidoyl thienamycin (MK0787): in vitro activity against anaerobic bacteria.

The in vitro activity of N-formimidoyl thienamycin (MK0787) was tested against 239 anaerobic bacteria clinical isolates: 70 of Bacteroides fragilis, 18 of B. distasonis, 16 of B. thetaiotaomicron, 10 of B. vulgatus, 24 of Bacteroides spp., 22 of B. melaninogenicus (all three subspecies), 26 of Fusobacterium spp., 10 of Peptococcus spp., 15 of Peptostreptococcus spp., 15 of Clostridium perfringens, and 13 of Clostridium spp. Ninety-five percent of the isolates were inhibited by less than or equal to 0.125 microgram/ml, and all were inhibited by less than or equal to 4 micrograms/ml.

Anaerobiosis↗

Moxalactam in the therapy of serious infections.

Sixty-seven patients were treated with moxalactam in a noncomparative trial of hospitalized patients; 32 had endometritis or chorioamnionitis, 12 had skin and soft tissue infections, 5 had osteomyelitis, 5 had pneumonia, 5 had urinary tract infections, 4 had arthritis, 2 had sepsis from an unknown source, 1 had endocarditis, and 1 had peritonitis. Bacteremia was present in 12 of these patients. Patients were given 3 to 12 g of moxalactam per day (mean, 6.24 g/day) in divided doses every 6 to 8 h. Seven patients were given intramuscular treatment for 3 to 20 days for part or all of their therapy. The rest were given intravenous treatment exclusively. Treatment was continued for 2 to 42 days (mean, 10 days). The dose and the duration of therapy were determined by the type of infection and the response of each patient. There were four treatment failures and one enterococcal-clostridial superinfection. Moxalactam was well tolerated. Allergic reactions led to the discontinuation of the antibiotic in three patients. Prolonged prothrombin and partial thromboplastin times were observed in 2 of 11 patients tested; in both instances in patients had severe underlying diseases, including malnutrition and alcoholism. Pain on intramuscular injection was noted in two patients receiving 1,500 mg, but not in five receiving a lower dose; in one case the pain forced the use of intravenous therapy after one dose, and in the other case the pain was mild and the patient was treated for 20 days. We concluded that moxalactam was effective in the treatment of the types of infections included in this study and produced few adverse reactions.

Bacterial Infections↗

Elevated mannose levels detected by gas-liquid chromatography in hydrolysates of serum from rats and humans with candidiasis.

We have developed a gas-liquid chromatographic method for identification of mannose in serum hydrolysates by utilizing peracetylated aldononitrile derivatives. Experimentally infected rats and human subjects with candidiasis were studied. Peaks in unknown samples were identified by co-chromatography of reference carbohydrates. Inositol was used as an internal standard. Mannose was identified in hydrolysates of normal rat (391.85 +/- 66.18 micrograms/ml) and human (297.87 +/- 77.81 micrograms/ml) sera. Significantly increased concentrations of mannose (greater than 526.21 micrograms/ml) were demonstrated in hydrolysates of sera from 26 of 36 (72%) experimentally infected rats tested 1 or more days after onset of infection. Significant increases (greater than 453.49 micrograms/ml) were also seen in humans with localized (6/15), transient (2/2), and disseminated (5/7) candidiasis. The concentrations were highest in patients with candidemia occurring either transiently or as part of disseminated infection. The concentrations in patients with localized candidiasis were lower but were still significantly greater than control. These data suggest that changes in mannose concentration, as measured, may serve as markers of candidiasis. The amount of mannose present may be in part a function of the extent of the infection.

Adult↗

Apparent ketoconazole failure in candidal cholecystitis.

Fungal acalculous cholecystitis is a rarely recognized complication of disseminated candidal infections. We report such a case of systemic candidiasis that developed in a man who was diabetic while he was receiving broad-spectrum antibiotic therapy for an infected foot ulcer. Ketoconazole, a new imidazole antifungal agent, was used successfully to treat the systemic candidal infection but it failed to eradicate the fungus in the biliary tract.

Antifungal Agents↗

Single-dose cefaclor therapy of urinary tract infection. Evaluation of antibody-coated bacteria test and C-reactive protein assay as predictors of cure.

The efficacy of single-dose (cefaclor, 2 g orally) and multidose (cefaclor, 250 mg orally three times a day for 10 days) antibiotic regimens in the therapy of acute uncomplicated urinary tract infections (UTI) in nonpregnant women were compared. The patient's clinical status and results of urine cultures were compared in retrospect with the results of the antibody-coated bacteria (ACB) test and C-reactive protein (CRP) test in order to determine if either test would predict the patient's response. Overall, 10 of 30 patients (33 percent) and 18 of 22 patients (81 percent) given single doses and multidoses, respectively, had negative urine cultures four weeks after completion of therapy. A negative urine culture at four weeks correlated with a negative ACB test utilizing the less inclusive criteria for negativity (less than 5 bacteria with fluorescence in 5 minutes of search) but not with a negative ACB test utilizing the more inclusive criteria (less than 10 percent bacteria with fluorescence) or with a negative CRP test. The cure rate in the ACB-negative single-dose group (7 of 9 patients) utilizing the less inclusive criteria for negativity was similar to the cure rate in the ACB-negative multidose group (8 of 10 patients). This study suggests that the ACB test, if properly standardized, might permit identification of a population of patients with UTI who would respond to single-dose cefaclor therapy.

Adult↗

Microbiologic and antibiotic aspects of infections in the oral and maxillofacial region.

An overview of infection as it applies to the oral and maxillofacial region has been provided. The following conclusions are drawn: odontogenic infections are caused by microbes found in the host's oral flora; cultures of purulent material generally will yield three to six anaerobes and one aerobe, (the aerobe is usually a Streptococcus species); Gram stains of purulent material can aid in therapeutic strategies; anaerobic as well as aerobic cultures are necessary to isolate all pathogens; pathogens found in infections of bite wounds reflect the oral flora of the aggressor; early postoperative wound infections are caused by the host's own flora, whereas later infections may be caused by hospital-acquired bacteria; and hepatitis B and herpes simplex virus are occupational hazards. Recommendations have been made for antimicrobial prophylaxis and for treatment. We recognize that some of these selections may be controversial. For instance, the value of prophylactic antibiotics in orthognathic surgery is not well defined; recommendations were made only in certain instances. However, in severe penetrating maxillofacial injuries with devitalized tissue, recommendations for antibiotics were for broad and prolonged coverage. In this instance, use of antibiotics is considered therapeutic and not prophylactic. In each instance, we tried to validate the selection. Our rationale has been to choose the antibiotics most active against the likely pathogens; additionally, consideration was given to drug toxicity and adverse reactions. We regard penicillin as the preferred agent for prophylaxis and treatment of most odontogenic infections. Alternative drugs include cephalosporins, doxycycline, and clindamycin. Erythoromycin and tetracycline are considered less effective than the former agents. Finally, we believe that successful treatment of infection depends as much on changing the microenvironment of the infected tissue by debridement and drainage as on appropriate antimicrobial therapy.

Actinomycosis↗

Shigellosis in day-care centres.

Increasing numbers of outbreaks of shigellosis in day-care centres have been reported to the Center for Disease Control since 1972. Investigations reveal certain unique epidemiological features of shigellosis in this setting. Attack-rates tend to be higher than in outbreaks in primary schools, and epidemiologically these outbreaks resemble those in custodial institutions. Person-to-person transmission is the usual mode of spread; secondary spread within households is common, and there may also be significant spread to the community at large. Preventive measures should be directed at children, staff, and the day-care centre environment. Control of outbreaks may require closing the centre and must include separation of infected and uninfected persons, judicious use of antibiotics, and correction of deficiencies in hygiene and health education. Improved surveillance of shigellosis in day-care centres will be an aid in efforts toward controlling this increasingly important public-health problem.

Adult↗

Synergism of oxacillin and gentamicin against enterococci.

Strains of enterococci isolated from 34 patients were studied for susceptibility to oxacillin and gentamicin alone and in combination. The minimal bactericidal concentrations of oxacillin and gentamicin for these strains ranged from 16 to 250 mug/ml (median 32 mug/ml) for oxacillin and 12 to 48 mug/ml (median 24 mug/ml) for gentamicin. The minimal bactericidal concentration of oxacillin for 50% of strains in the presence of 12, 6, 3, and 1.5 mug of gentamicin per ml, respectively, was 2, 8, 16, and 32 mug/ml. The combination of oxacillin and gentamicin at clinically attainable serum levels was synergistically bactericidal against 27/34 (80%) of these strains using strict criteria. This report reconfirms the original observation that antibiotics which affect the synthesis of bacterial cell walls combine synergistically with aminoglycosides against enterococci. This is so even though enterococci are far more resistant to oxacillin than to penicillin or ampicillin. In addition, this report suggests that the combination of oxacillin and gentamicin administered in the usual dosages includes enterococci in its bactericidal spectrum.

Drug Synergism↗