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Biomedical subjects

L O Gentry

Publications and source records attributed to L O Gentry.

At least 73 records · Page 4Linked to original sources

Ticarcillin plus clavulanic acid (Timentin) therapy for osteomyelitis.

Timentin is an exciting new antibiotic agent that is a combination of ticarcillin and clavulanic acid. Forty-seven patients with osteomyelitis received 3.1 g of Timentin intravenously every six hours. The mean duration of therapy was 32 days. The diagnosis was made by bone biopsy; bone biopsy was repeated at the completion of therapy. The bacterial etiology was predominately gram-positive organisms. Of the organisms isolated, Staphylococcus aureus was the most common isolate and represented 39 percent of the total isolates. Streptococcus species were isolated in 13 percent, Group D Enterococcus in 15 percent, Pseudomonas aeruginosa in 10 percent; 23 percent of the isolates were other gram-negative organisms. All but one organism were initially sensitive to Timentin. Three resistant organisms were isolated during therapy. Twenty-seven patients were classified as having a cure, based on no growth on repeat bone biopsy cultures and clinical signs of bone healing. Twenty-two patients returned for follow-up (one to nine months after therapy) and had no evidence of infection; however, because of the short follow-up period, these patients were classified as showing improvement. Six patients had adverse reactions to Timentin: two had mild allergic phenomena and two had prolonged bleeding times. In all four, therapy was discontinued. Two patients had a transient, mild elevation in the level of serum glutamic-pyruvic transaminase (less than twice normal levels). This new agent looks exciting for therapy of both gram-positive and gram-negative bacterial osteomyelitis.

Adolescent↗

Treatment of skin, skin structure, bone, and joint infections with ceftazidime.

The collective experience with ceftazidime in the treatment of skin, soft tissue, bone, and joint infections is presented. Patients were treated with dosages ranging between 25 and 150 mg/kg per day for between five and 42 days. A total of 570 patients with skin and skin structure infections were treated with ceftazidime. Comparative studies, using either cefamandole or tobramycin plus ticarcillin as control drugs, included 239 patients. There were 600 evaluable patients in five categories of skin or skin structure infection: 252 patients had cellulitis, 107 had wound infections, 103 had abscesses, 90 had skin ulcers, and 48 had other miscellaneous infections. Bacteriologic etiologies were gram-negative rods in 303 episodes, gram-positive cocci in 241, anaerobes in 14 episodes, and miscellaneous other organisms in 48 episodes. Overall bacteriologic efficacy was 90 percent in ceftazidime-treated infections and 76 percent in control-treated infections. The clinical efficacy of ceftazidime against infections caused by the gram-positive cocci, particularly Staphylococcus species, was surprisingly good (85 percent) and similar to the efficacy achieved in the cefamandole-treated patients (85 percent). The overall clinical efficacy for ceftazidime was 93 percent. One hundred thirty-four patients with bone or joint infections received ceftazidime. The dosages were similar, but the duration of treatment was the longest in this group. Ceftazidime treatment was compared with standard dosages of tobramycin and ticarcillin in 11 patients. Osteomyelitis was cured in 58 of the 101 patients who received ceftazidime. In five patients, osteomyelitis failed to respond: in two, a resistant Pseudomonas strain emerged; the other three failures were due to persistent bone sequestra. Thirty-eight patients showed improvement. Of those in the tobramycin and ticarcillin group, nine of 10 evaluable patients (90 percent) showed either cure or improvement. The one failure was due to a persistent sequestrum. Thirteen patients with septic arthritis and seven with bursitis were also treated with ceftazidime; the overall cure rate was 75 percent. Adverse reactions to ceftazidime were severe, and the drug was discontinued in 13 of 570 (2.3 percent) patients with skin or skin structure infections and in five of 134 (3.7 percent) patients with bone and joint infections. These data suggest that ceftazidime is effective as monotherapy in the treatment of skin, skin structure, bone, and joint infections, and that it may be more efficacious against staphylococcal infections than predicted from in vitro data.

Abscess↗

Imipenem/cilastatin in the treatment of osteomyelitis.

Thirty-four patients with osteomyelitis were treated for a mean of 32.5 days with 2 to 4 g per day of imipenem/cilastatin. Twenty-six infections involving the lower extremities were associated with accidents and prosthesis implantation, and 19 of 34 patients had more than one organism isolated. Gram-positive and gram-negative organisms were equally represented, but follow-up bone culture samples showed only 11 percent of gram-positive organisms persisted versus 23 percent of gram-negative organisms. Seventy-four percent of patients were cured or improved, and failures were related to resistant organisms and the inability to perform adequate surgical debridement. Adverse drug side effects included nausea, diarrhea, liver enzyme elevations, and neutropenia, but discontinuation of treatment was required in only three patients. Imipenem/cilastatin holds promise as monotherapy in complicated polymicrobial osteomyelitis.

Adult↗

Role for newer beta-lactam antibiotics in treatment of osteomyelitis.

Monotherapy of osteomyelitis with the newer broad-spectrum beta-lactam antibiotics has become attractive because of the efficacy, safety, and cost of these antibiotics when compared with conventional combination therapy. Imipenem/cilastatin is a recent and promising addition to this antibiotic family. Experience with imipenem/cilastatin and that reported for cefotaxime, ceftazidime, and ceftizoxime in the treatment of biopsy-proved osteomyelitis was compared, using data from published reports from five centers. Two hundred forty-three patients were evaluable: 34 were treated with imipenem/cilastatin, 84 with cefotaxime, 122 with ceftazidime, and 33 with ceftizoxime. Staphylococcus aureus was isolated by 80 bone cultures and was the most common single species encountered. There were 75 isolates of Pseudomonas aeruginosa, 113 mixed Enterobacteriaceae species, 115 mixed gram-positive and -negative isolates of miscellaneous species, and 30 anerobic isolates. Polymicrobial infection was present in 101 cases (41.6 percent). Failure rates were similarly low in all groups (10 to 30 percent). However, resistance developed during therapy in all groups with P. aeruginosa. Side effects were predictably few, but reversible neutropenia, pseudomembranous colitis due to Clostridium difficile, and nausea required therapy to be discontinued in seven patients. Imipenem/cilastatin should prove to be a very effective and relatively safe single agent for treatment of osteomyelitis.

Adult↗

Effects of apalcillin on platelet function in normal volunteers.

We investigated the effects of apalcillin on blood coagulation and platelet function. The drug was administered to 21 human volunteers in daily intravenous doses of 75, 150, and 225 mg/kg. These doses evoked abnormalities in platelet aggregation similar to those found with piperacillin and mezlocillin and less striking than those produced by carbenicillin and ticarcillin. Plasma coagulation as measured by prothrombin time, activated partial thromboplastin time, thrombin time, and fibrinogen concentration was not affected. There were consistent and major reductions in plasma antithrombin III activity, particularly at the two higher dose levels. Of 21 patients, 7 (33%) also manifested maculopapular skin rashes which resolved after discontinuation of the drug.

Adult↗

Successful treatment of invasive aspergillosis in a heart transplant patient.

Infection continues to be a major cause of mortality in cardiac transplant patients, and even though there has been significant progress in diagnosing and treating many infectious disease problems, invasive aspergillosis in the transplant patient represents a serious and usually fatal complication. Even with successful early diagnosis, the use of free amphotericin B (a polyene antibiotic) has failed to cure disseminated infection. We report the case of a 46-year-old transplant patient who failed to respond to treatment with free amphotericin B after a 7-day period of treatment for biopsy-proven pulmonary aspergillosis. However, a subsequent substitution of a liposomal form of amphotericin B was used, and the patient responded well to a total dose of 1.5 mg. After 7 months, the patient continues free of infection. This experience suggests that the introduction of liposomal amphotericin B may give new hope for treating an otherwise lethal infection.

Journal Article↗

Inhibition of povidone-iodine's bactericidal activity by common organic substances: an experimental study.

An in vitro study demonstrated that some organic substances commonly present in the surgical field inhibit the bactericidal activity of dilute povidone-iodine solutions. The degree of inhibition was inversely proportional to the concentration of the povidone-iodine solutions and it was greatest by blood, followed by pus, fat, and glove powder. The pattern of bacterial kill was virtually identical for all the strains tested. The most likely explanation for this phenomenon is that iodine is bound by the organic substances, decreasing the iodine available for bacterial kill. To obtain an optimal benefit, we suggest eliminating these substances from the operative site or wound when possible before the use of povidone-iodine solution.

Bacteria↗

Perioperative antibiotic therapy for penetrating injuries of the abdomen.

From 1979 through 1981, 152 patients with penetrating injuries of the intra-abdominal gastrointestinal tract were placed on one of three different perioperative antibiotic regimens in a prospective randomized fashion. The three regimens were A) cefamandole 2 grams every 4 hours, B) cefoxitin 2 grams every 6 hours, and C) ticarcillin 3 grams every 4 hours and tobramycin 1.5 mg/kg every 8 hours. Antibiotics were administered intravenously before and for 48 hours following surgical exploration and repair. The three treatment groups were similar with respect to age, average number of organ injuries, and distribution of organ injuries. Cefoxitin-treated patients experienced uneventful recoveries more often than cefamandole-treated patients (94% vs. 80.3%, p less than 0.05) when the incidence of gram-negative wound infection and intra-abdominal abscess formation was considered, while the number of patients who experienced uneventful recoveries in the ticarcillin-tobramycin group was not statistically different from the other two groups of patients. Bacteroides fragilis was isolated from three of the six abscesses occurring in the cefamandole-treated group, while no anaerobes were isolated from abscesses in patients treated with either of the other two regimens. The results of this study suggest that the most effective perioperative antibiotic regimen for patients with penetrating gastrointestinal wounds should possess activity against both aerobic and anaerobic flora of the bowel.

Abdomen↗

Latex agglutination test for detection of Candida antigen in patients with disseminated disease.

A latex agglutination test has been devised which allows detection of a circulating antigen in patients with systemic infection due to Candida albicans, Candida tropicalis and Candida parapsilosis. Latex is sensitized with serum from rabbits immunized with whole heat killed Candida albicans blastoconidia. The active component of this serum is IgG. Control latex, used to differentiate non-specific agglutination, is sensitized with the same dilution of serum from a rabbit without antibody to Candida species. Sera from a number of patient groups were tested. While none of the hundred normal controls had an antigen titer of greater than or equal to 1:4, 30 of 33 patients with documented disseminated candida infection had antigen titers of 1:4 to 1:32. Two of the 33 gave false negative results, and one caused nonspecific agglutination. In all patients who recovered after antifungal therapy antigen levels returned to within the range found in normal controls.

Adult↗

A random comparative trial of 0.25, 0.5 and 1.0 g ceftazidime twice daily in urinary tract infection.

One hundred and sixty-six patients with complicated and uncomplicated urinary tract infections were randomized to therapy with either 0.25, 0.50 or 1.00 g of ceftazidime im or iv twice daily for five days. Bacteriological data were complete in 138 patients. Escherichia coli caused 50% of all infections, Klebsiella and Enterobacter spp. caused 10.9%, Pseudomonas spp caused 10.9%, Proteus spp. caused 10.7%, and 8.7% were caused by other Gram-negative bacteria. Staphylococcus and Streptococcus spp. caused 9.4%. Cure rate was lowest in infections caused by Pseudomonas (53.3%) and Proteus spp. (64.3%); however, most of these infections were complicated. No significant dose-related difference in efficacy was observed, but the 0.25 g dose had the lowest cure rate in each category. Nausea was the only side effect. The most common laboratory abnormalities were elevated liver function tests. Minimal changes in haematological and renal function were seen.

Adult↗

Double-blind comparison of bismuth subsalicylate and placebo in the prevention and treatment of enterotoxigenic Escherichia coli-induced diarrhea in volunteers.

Enterotoxigenic Escherichia coli cause most traveler's diarrhea in Third World countries. We tested bismuth subsalicylate as prophylactic therapy and as treatment for enterotoxigenic E. coli-induced diarrhea. Thirty-two healthy hospitalized volunteers were challenged orally with enterotoxigenic E. coli, strain H10407 (serotype 078:K80:H11). Administration of 600-mg doses of bismuth subsalicylate or placebo was begun 8 h before bacterial challenge. Doses were taken at 8 h and 2 h before, and at 2 h and 4 h after, the E. coli challenge and were continued four times a day for 3 additional days. The maximum prophylactic bismuth subsalicylate dose was 9.6 g. Those experiencing diarrhea were rerandomized to receive bismuth subsalicylate or placebo, given as 300 mg every 30 min for a total of 2.4 g of bismuth subsalicylate, in eight doses. Diarrhea occurred in 9 of the 16 (56%) subjects receiving placebo and in 2 of the 15 (13%) subjects receiving bismuth subsalicylate, p less than 0.03. This study confirms the effectiveness of bismuth subsalicylate in preventing traveler's (enterotoxigenic E. coli) diarrhea, and shows that bismuth subsalicylate in other than liquid form is effective. Enterotoxigenic E. coli were recovered less frequently from those receiving bismuth subsalicylate than from those receiving placebo, suggesting that bismuth subsalicylate prevents diarrhea by reducing the number or multiplication of enterotoxigenic E. coli. In vitro studies revealed that bismuth subsalicylate and its components each were bactericidal at concentrations possibly attained during the clinical trial.

Antidiarrheals↗

Endogenous endophthalmitis among patients with candidemia.

Thirty-eight patients with fungemia were examined prospectively for development of endophthalmitis. Endophthalmitis was present in 10 of 27 (37%) patients with Candida albicans fungemia. Only one patients with nonalbicans fungemia developed endophthalmitis. Of the preselected factors studied, only hemodialysis and parenteral hyperalimentation correlated with an increased incidence of endophthalmitis. Antibody titers by latex agglutination were of little predictive value for endophthalmitis. Antigen titers by latex agglutination were performed in four cases with endophthalmitis. Antigenemia was demonstrated in three of the four patients, all of whom had negative antibody serologies. Although inconclusive, the preliminary data indicate the test may prove to be of clinical value. Periodic ophthalmoscopic examinations should be considered mandatory in the evaluation of patients with fungemia.

Candidiasis↗

Plate method for detection of phospholipase activity in Candida albicans.

Intracellular phospholipase activity has previously been detected in Candida albicans. A plate method is described which allows rapid detection and measurement of the extracellular activity in a number of clinical isolates. The ratio of colony diameter to diameter of the dense white zone of precipitation around phospholipase positive colonies, (Pz value), correlates with hydrolysis of [14C]phosphatidylcholine by concentrated culture filtrates of selected test isolates. A large variation in phospholipase activity is found between different isolates of C. albicans, however the Pz value is constant for any one isolate regardless of the site from which it is recovered in the patient. Fifty five % of fresh blood isolates are positive and these are also the most potent phospholipase producers. Fifth % of wound isolates and 30% of urine isolates are also positive. A larger sample group must be studied, however, before it can be determined whether these differences are highly significant.

Blood↗

Prevalence of penicillin-resistant pneumococci in Houston, Texas.

Pneumococci resistant to penicillin have been reported in increasing numbers world-wide. A survey for resistance to penicillin G in 222 clinical isolates taken from patients in Houston is reported here. Thirteen (5.9%) of the isolates screened exhibited moderate levels of resistance with MIC's ranging from 0.125-0.5 microgram/ml. The authors recommend routine screening for pneumococcal resistance in isolates from blood, cerebrospinal fluid and tissue exudates.

Humans↗

Randomized comparative study of moxalactam and cefazolin in the treatment of acute urinary tract infections in adults.

Eighty-nine patients with clinical and laboratory evidence of acute urinary tract infection were randomized to therapy with either moxalactam (500 mg) or cefazolin (1 g) every 12 h. Escherichia coli was the predominant pathogen in both groups (92.6 versus 90.2%). Therapy was continued for 3 days after the patient defervesced. The minimum hospital stay was 5 days. Sequential urine cultures were obtained on day 3, at discharge, and 5 to 10 days after the cessation of therapy. THe average duration of hospital stay was 5.6 days for both groups of patients. THe incidence of recurrent infection was similar in uncomplicated patients (9.1 versus 10%) and in complicated patients with a condition predisposing them to urinary tract infections (43 versus 42%). Moxalactam-treated patients had a higher incidence of reversible hepatic enzyme elevation (36%) and Streptococcus faecalis superinfections (12.2%). Moxalactam is as effective as cefazolin for the elimination of gram-negative pathogens from the urine of patients with acute urinary tract infections, but it is associated with a higher incidence of reversible side effects.

Adult↗

Endogenous Candida albicans endophthalmitis in the rabbit. Chemotherapy for systemic effect.

Progressive endogenous Candida albicans endophthalmitis was established in rabbits by intravenous (IV) injection of blastospores (2.0 to 5.0 x 10/kg). Severity of infection was directly related to the strain and inoculum size. Intravenous amphotericin B (1.0 mg/kg/day), IV amphotericin B methyl ester ascorbate (5.0 mg/kg/day), and oral ketoconazole (80 mg/kg/day) effectively prevented or reduced the severity of infection when therapy was initiated 24 hours following inoculation of blastospores and continued for five to seven days. Intravenous miconazole (30 mg/kg/day) was ineffective in this model. Intravenous amphotericin B(1.0 to 2.0 mg/kg on alternate days), IV amphotericin B methyl ester ascorbate (5.0 mg/kg/day), and oral ketoconazole (80 mg/kg/day reduced the severity of C albicans endophthalmitis when therapy was initiated seven days following injection of blastospores and continued for 28 days. Oral flucytosine (75 and 150 mg/kg/day in four doses) produced uniformly fatal hepatic necrosis in uninfected rabbits.

Amphotericin B↗