Escherichia coli bacteremia in the squirrel monkey. I. Effect of cobra venom factor treatment.

Squirrel monkeys were significantly depleted of complement by a nontoxic protein constituent of cobra venom, and the influence of cobra factor (CoF) treatment on the course of Escherichia coli bacteremia was studied. Striking neutropenia occurred rapidly in control animals while the rate of occurrence of neutropenia was 20 to 30 times slower in the CoF-treated animals, suggesting that the E. coli-induced neutropenia was at least partially a complement-mediated response. In the CoF-treated monkeys, the initial rate of clearance of the E. coli from the circulation tended to be slower and the resultant levels of bacteremia were higher than in control animals. These observations are consistent with a hypothesis that complement-mediated neutrophilic leucocyte function is an important host defense mechanism in gram-ngeative bacillary bacteremia.

Inhibition of neutrophil chemotaxis by 4-hydroxycyclophosphamide.

4-Hydroxycyclophosphamide, phosphoramide mustard, and nor-nitrogen mustard are compounds considered as candidates for the biologically active, alkylating metabolite of cyclophosphamide. These compounds were tested for inhibition of chemotaxis in neutrophils from normal human donors. Of those tested, only 4-hydroxycyclophosphamide caused a significant (p less than 0.01) decrease in the chemotactic index. The chemical precursor of 4-hydroxycyclophosphamide, 4-hydroperoxycyclophosphamide, caused a barely significant (p less than 0.05) decrease; 4-ketocyclophosphamide had no effect.

Haemophilus parainfluenzae infective endocarditis.

Seven young to middle-aged patients with Haemophilus parainfluenzae endocarditis are reported. Three patients had underlying heart disease and three patients had recent events predisposing for endocarditis. The clinical presentation was subacute or acute and new pathologic murmurs were uncommon. Diagnosis was prolonged because of difficulties in isolating the organism. Routine subculturing of blood cultures to chocolate agar with incubation in CO2 is recommended. A prominent complication, occurring in six patients, was major arterial occlusion secondary to emboli. Antibiotic control of infection was difficult and best achieved by the concomitant administration of ampicillin and gentamicin. Killing curves proved useful in assessing antibiotic efficacy. There were two medical failures and one death in the series. It appears H. parainfluenzae endocarditis is characterized by distinctive clinical features, difficult in vitro isolation of the organism, and the necessity for combination antibiotic therapy.

Oral ciprofloxacin therapy for chronic contiguous osteomyelitis caused by aerobic gram-negative bacilli.

Twenty adult patients with chronic contiguous osteomyelitis caused by aerobic gram-negative bacilli were enrolled in an open, prospective cooperative study to determine the effect of oral ciprofloxacin therapy in a dosage of 750 mg every 12 hours. There were 14 men and six women, with a mean age of 55 years. Fifteen of the 20 patients had undergone previous unsuccessful attempts at therapy; seven of the 20 patients had clinically important underlying diseases. Osteomyelitis involved the sternum in three patients and the bones of the lower extremity in 17 patients. Initial surgical debridement was performed in 15 of 20 patients. The predominant organism isolated was Pseudomonas aeruginosa, which was found as a single pathogen in 13 patients and as part of a polymicrobic flora in three patients. Based on posttreatment follow-up of seven to 21 months, clinical cure was achieved in 13 of 20 (65 percent) patients and bacteriologic cure was achieved in 14 of 20 (70 percent) patients. Minimal inhibitory concentrations of ciprofloxacin against P. aeruginosa increased during therapy in four of 16 (25 percent) patients. Minor gastrointestinal side effects occurred in five patients. Oral ciprofloxacin was an effective and safe therapy in patients with chronic contiguous osteomyelitis due to aerobic gram-negative bacilli.

A randomized comparison of the safety and efficacy of once-daily gentamicin or thrice-daily gentamicin in combination with ticarcillin-clavulanate.

PURPOSE: The primary purpose of the clinical trial was to assess the safety and efficacy of once-a-day compared with three-times-a-day gentamicin in patients with serious infections who had protocol-determined peak serum aminoglycoside concentrations. PATIENTS AND METHODS: A total of 249 hospitalized patients with suspected or proven serious infections were randomized in a 2:2:1 ratio to gentamicin given three times a day with ticarcillin-clavulanate (TC), gentamicin once a day with TC, or ticarcillin-clavulanate (TC) alone. The gentamicin once-a-day dosage for patients with estimated creatinine clearance values of > or =80 mL/min was 5.1 mg/kg. With lower creatinine clearance estimates, the mg/kg dosage of gentamicin was decreased, and the dosage intervals (once daily or three times a day) were maintained. Evaluability required documentation of achievement of protocol-defined peak serum gentamicin levels. RESULTS: Of the total 175 evaluable patients, there were no significant differences found between treatment regimens with respect to clinical or microbiologic efficacy. Bedside audiometry proved impractical due to the frequency of altered mental state in ill patients. Based on the traditional increase in serum creatinine values from baseline values, no differences in renal toxicity between the treatment groups was identified. When changes in renal function were reanalyzed based on maintaining, as opposed to worsening, of renal function, preservation of renal function was better in the gentamicin once-a-day patients as opposed to the gentamicin three-times-a-day patients, P <0.01. CONCLUSIONS: Gentamicin once a day plus TC, gentamicin three times a day plus TC, and TC alone had similar effects in seriously ill hospitalized patients. The incidence of nephrotoxicity was similar in the three treatment groups. Using a nonvalidated post-hoc analysis, renal function was better preserved in gentamicin once-a-day + TC and TC-only patients as opposed to gentamicin three-times-a-day + TC.

Prophylactic antibiotics and the insertion of permanent transvenous cardiac pacemakers.

Prophylactic antibiotics are prescribed frequently for patients requiring permanent transvenous cardiac pacemakers, despite a paucity of data indicating effectiveness. A 10 year retrospective analysis was performed of 298 pacemaker insertion procedures involving 204 patients. On the basis of prestudy criteria relating to timing and dosage of antibiotics, the use of prophylactic antibiotics was judged as adequate or inadequate. There were no postoperative infections in the 108 battery pack replacement procedures despite no or inadequate use of antibiotics in 49 procedures. There were nine infections in the 190 battery pack plus pacing wire procedures for an infection rate of 5 percent. There was no significant difference in infection rate between the group given prophylactic antibiotics and the group given no or inadequate prophylactic antibiotics. Of the 190 battery pack plus pacing wire procedures, no infections occurred in the 50 procedures in which surgical drains were not used (p less than 0.003). In the 140 procedures in which drains were used, there was no correlation between wound infection and absent or inadequate coverage with prophylactic antibiotics. Two severe bacteremic Staphylococcus aureus infections occurred in two patients not given prophylactic antibiotics. The other seven infections were clinically indolent. These results suggest the following: (1) There is no need for prophylactic antibiotics in battery pack replacement procedures; (2) prophylactic antibiotics may decrease the severity of infection in battery pack plus pacing wire procedures; (3) surgical drains should be avoided in battery pack plus pacing wire procedures. A prospective controlled study is necessary to confirm these results.

Surgical approach to extensive suppurative thrombophlebitis of the central veins of the chest.

Suppurative thrombophlebitis is a potentially lethal intravascular infection associated with the usage of intravenous catheters. Conventional approaches to management include ligation and excision of involved venous structures. These measures may not be feasible in all situations. This paper describes the successful medical/surgical management of a patient with suppurative thrombophlebitis of the major vessels of the chest. When suppurative thrombophlebitis extends into the large central veins and antibiotic therapy fails, surgical intervention may be necessary.

Mycobacterium gordonae in fiberoptic bronchoscopes.

BACKGROUND: Failure of high-level disinfection of bronchoscopes has caused several outbreaks of nosocomial infection or pseudoinfection involving mycobacteria. METHODS: Inocula (10(5) colony-forming units/ml and 10(8) colony-forming units/ml) of a clinical Mycobacterium gordonae isolate were used to contaminate bronchoscopes. Glutaraldehyde, iodophor, and peracetic acid disinfectants were evaluated in manual and automated disinfection procedures after 10- to 20-minute exposures at 20 degrees and > or = 25 degrees C. RESULTS: Four of five manual disinfectant procedures failed to eliminate experimental M. gordonae infection after 10-minute exposure at 20 degrees C. All five manual procedures tested at 20 degrees C were effective after 20-minute exposure to the five disinfectants (two 2% alkaline glutaraldehyde preparations, 3.2% alkaline glutaraldehyde, 75 ppm iodophor, and 0.5% glutaraldehyde-0.03% phenolic). Three of four manual (one 2% glutaraldehyde, 3.2% glutaraldehyde, and 0.5% glutaraldehyde-0.03% phenolic) and three automated (one 2% glutaraldehyde, 0.5% glutaraldehyde-0.03% phenolic, and 0.2% peracetic acid) disinfectant procedures eliminated contamination after a 10- to 12-minute exposure at > or = 25 degrees C. Effective total cycle times for the three automated procedures ranged from 20 to 45 minutes. CONCLUSIONS: Previously Environmental Protection Agency-approved tuberculocidal agents may be ineffective against M. gordonae when used according to label claims under normal clinical conditions. A minimum 20-minute exposure time at 20 degrees C is necessary for manual disinfection methods. Higher temperatures may improve disinfectant efficacy. Newer automatic disinfection machines may be as effective as traditional manual methods and also may reduce hazards to employees.

Use of antimicrobial agents in renal failure.

Many antimicrobial agents are excreted primarily by the kidneys, and hence, to avoid toxicity and maintain efficacy, dosage adjustments are necessary. After estimating a patient's creatinine clearance, an appropriate dosage adjustment is easily accomplished. The adjustments for aminoglycosides are simplified by the use of a suggested once-daily, or once every other day dosage regimen.

Zidovudine pharmacokinetics in five HIV seronegative patients undergoing continuous ambulatory peritoneal dialysis.

A few reports in the literature describe zidovudine (AZT) pharmacokinetics in patients undergoing hemodialysis; however, the effect of continuous ambulatory peritoneal dialysis (CAPD) on the drug's disposition has not been studied. The pharmacokinetics of AZT were evaluated in five patients, age 37-62 years, who were seronegative for the human immunodeficiency virus and were undergoing CAPD. Serial plasma, urine, and dialysate samples were collected after oral administration of AZT 200 mg. Samples were assayed using radioimmunoassay (RIA). Model-independent analysis was used to determine total plasma clearance, apparent volume of distribution, mean residence time, and half-life. Net peritoneal dialysis clearance was calculated to measure the effect of CAPD on AZT disposition. We found wide interpatient variability in AZT pharmacokinetics. Peak serum concentrations ranged from 0.3-47.8 microns and area under the curve from 0.5-26.1 mg x hour/L. These differences resulted in corresponding differences in clearance (range 66-3176 ml/min/1.73 m2) and volume of distribution (range 16-825 L). Interpatient variability in glucuronidation may partially account for this variability. Net peritoneal dialysis clearance of AZT was 5 ml/minute. Although the effect of peritoneal dialysis on AZT disposition was negligible, clinicians should be aware of the large differences in the way in which individual patients with renal dysfunction handle this drug.

Study of different off-line sample processing procedures and the measurement of antibiotic and antiviral levels in human serum by high-performance liquid chromatography.

We attempted to devise a preparation method for clinical samples that could be used for all antibiotics and antivirals. We studied thirteen antibiotics, including five penicillins, four cephalosporins, metronidazole, ofloxacin, and sulfamethoxazole and four protease inhibitors including indinavir, retonavir, nelfinavir, and sequinavir. We compared four sample preparation techniques including solvent precipitation, filtration and resin column. We employ HPLC methods based on a minimal number of columns and mobile phases. We were unable to find one sample preparation method that could be used for all antibiotics and antivirals. But, we did develop an algorithm for determining optimal processing procedures for all drugs.