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Biomedical subjects

C G Cobbs

Publications and source records attributed to C G Cobbs.

At least 19 recordsLinked to original sources

In vitro activity of sparfloxacin and three other fluoroquinolones against methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis.

Fluoroquinolones are variably active against methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant Staphylococcus epidermidis (MRSE). The purpose of this study was to test the in vitro susceptibility of 50 isolates each of MRSA and MRSE to four of the new fluoroquinolones--sparfloxacin, ciprofloxacin, ofloxacin and norfloxacin--and to see if resistance could be induced in five susceptible strains of each species by serial passages with increasing concentrations of drug. A standard microdilution technique was used to determine minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) of each drug for each isolate. Agar dilution plates were also prepared containing concentrations of drug varying from one-half of the reported MIC to 128 times the reported MIC, and microorganisms persisting were serially passaged. Initially, 98% of the strains of MRSA were susceptible to the fluoroquinolones. MBCs were essentially identical to MICs. Similarly, 96% of the strains of MRSE were susceptible. Following exposure to increasing concentrations of each fluoroquinolone, resistance appeared to emerge less rapidly to sparfloxacin and ofloxacin than to norfloxacin and ciprofloxacin.

Anti-Infective Agents

In vitro comparison of cilofungin alone and in combination with other antifungal agents against clinical isolates of Candida species.

Cilofungin, a lipopeptide antifungal agent, was tested for in vitro activity alone and in combination with ketoconazole, itraconazole, flucytosine and amphotericin B against 102 clinical isolates of Candida species. At 48 hours all isolates of Candida albicans, Candida tropicalis, Candida paratropicalis and Candida glabrata were inhibited by less than or equal to 5 meg/ml of cilofungin. In contrast, the MIC90 for Candida krusei was 10 mcg/ml and for Candida parapsilosis greater than 40 mcg/ml. The interaction of combinations of cilofungin with amphotericin B, itraconazole, ketoconazole and flucytosine was additive or indifferent at 48 hours for 100%, 88%, 78% and 70% of all Candida species isolates, respectively. Overall, cilofungin demonstrated good activity in vitro against most Candida species isolates.

Amphotericin B

Comparison of cilofungin and amphotericin B for therapy of murine candidiasis.

We compared the efficacies of cilofungin and amphotericin B treatment in a murine model of disseminated candidiasis. Three different dosages of each drug plus controls were evaluated. Statistically improved survival was noted only among mice treated with 1 mg of amphotericin B per kg of body weight (P less than 0.05). While all amphotericin B regimens and the two lower-dosage cilofungin regimens significantly reduced yeast cell counts in kidneys compared with the controls, the amphotericin B-treated mice had a significantly higher percentage of sterile kidneys following therapy compared with those treated with cilofungin (P = 0.0001).

Amphotericin B

Diseases that mimic herpes simplex encephalitis. Diagnosis, presentation, and outcome. NIAD Collaborative Antiviral Study Group.

A total of 432 patients underwent brain biopsy for presumptive herpes simplex encephalitis. Three patient groups were identified. The first group, 195 patients (45%), had herpes simplex encephalitis confirmed by the isolation of herpes simplex virus from brain tissue at biopsy (193 patients) or autopsy (2 patients). The second group, 95 patients (22%), had diseases that were identified but that were not caused by herpes simplex virus. Three subgroups were recognized: (1) 38 patients (9%) with treatable disease, (2) 40 patients (9%) with nontreatable but diagnosed viral infection, and (3) 17 patients (4%) with identified diseases neither of viral etiology nor treatable. The third group, 142 patients (33%), remained without a diagnosis. Clinical presentation of patients in the second group was similar to that of those with herpes simplex encephalitis and those without a diagnosis. Patients in the subgroup with nontreatable but diagnosed viral infections had the greatest likelihood of returning to normal.

Adolescent

Bacteriostatic versus bactericidal activity.

Antibiotics alone or in combination may either inhibit or kill bacteria. Laboratory methods are available to determine the activity of various antimicrobial agents and can aid the physician in selecting appropriate antimicrobial therapy for specific infectious disease disorders. A few infectious processes appear to require bactericidal antimicrobial therapy for cure. Additional multicenter trials of the ability of a standardized SBT to predict therapeutic outcome in specific bacterial diseases are required.

Animals

Q fever endocarditis.

Q fever endocarditis, which is seen most often in Great Britain and Australia, has been rarely observed in the United States. A patient with an eight month febrile illness who had signs and symptoms of endocarditis and serologic studies diagnostic of Q fever endocarditis is reported. A history of extensive travel makes it unclear where he originally contracted the disease. Q fever endocarditis is probably underdiagnosed and should be looked for in any case of culture negative endocarditis or chronic fever of unknown origin.

Aged

Pseudallescheria boydii infection of the central nervous system in a cardiac transplant recipient.

We have described a cardiac transplant recipient with fatal Pseudallescheria boydii infection of the central nervous system. Unusual features included meningitis without brain abscess and noncommunicating hydrocephalus due to exuberant growth of the organism in the ventricular fluid. Long-term amphotericin B administration may have played a role in the development of this infection.

Adult

In vitro activity of piperacillin, ticarcillin, and mezlocillin alone and in combination with aminoglycosides against Pseudomonas aeruginosa.

A total of 103 isolates of Pseudomonas aeruginosa were studied to compare the in vitro effectiveness of three beta-lactam antibiotics (piperacillin, ticarcillin, and mezlocillin) when used alone and in combination with four aminoglycosides (tobramycin, gentamicin, amikacin, and netilmicin). All drugs were tested as single agents against a standard inoculum (5 X 10(5) CFU/ml). The three antipseudomonal penicillins were also tested against the isolates at a higher inoculum concentration (10(7) CFU/ml). Synergy testing was performed by the two-dimensional checkerboard method and was defined by a fractional bactericidal index of less than or equal to 0.5 and bacterial killing accomplished at antibiotic concentrations no greater than those achievable in serum. All combinations were assessed for synergy. The degree of synergy was further analyzed by dividing the isolates into groups based on their susceptibility and resistance to the individual agents in the combination. The overall effectiveness of the various aminoglycoside-antipseudomonal penicillin combinations was assessed regarding their ability to kill the isolates either as single agents or through synergy. Piperacillin was the most active antipseudomonal penicillin, and tobramycin and amikacin were the most active aminoglycosides when used as single agents. When tested against isolates at a higher inoculum concentration, ticarcillin was significantly more active than the other beta-lactams. The highest degree of overall synergy was noted with gentamicin-ticarcillin (78.2% of strains) and amikacin-piperacillin (77% of strains). When assessed for overall effectiveness, all combinations containing amikacin were the most active. The combination of amikacin-piperacillin was the most effective, with activity against 96% of all isolates.

Aminoglycosides

Indications for cardiac surgery in patients with active infective endocarditis.

Currently, absolute indications for valve replacement during active infective endocarditis include severe heart failure, the presence of an infecting microorganism that is not susceptible to available antimicrobial agents, and, in patients with an infected prosthetic valve, an unstable device. Relative indications include an etiologic microorganism other than a susceptible Streptococcus, relapse after presumed effective therapy, evidence of intracardiac extension of the infection, two or more systemic emboli, vegetations large enough to be demonstrated by echocardiography, and, in patients with an infected prosthetic device, early disease and periprosthetic leak. With use of data from the medical literature, a study generated by the cardiovascular surgical group at the University of Alabama School of Medicine, and a brief cost analysis, a point system was constructed to assist in decision-making concerning surgery in patients with active infective endocarditis. The usefulness of this system will depend on experience generated from its utilization in a larger number of patients as well as new data relative to a more complete understanding of the risks and benefits of surgery in this condition.

Actuarial Analysis

Cefotaxime aminoglycoside interactions.

Minimum inhibitory concentrations and minimum bactericidal concentrations were determined for cefotaxime, gentamicin, tobramycin and amikacin and for the combination of cefotaxime and each of the aminoglycosides in vitro against 200 strains of Enterobacteriaceae. 91% were susceptible to cefotaxime, 93.5% were susceptible to gentamicin, 89.5% were susceptible to amikacin and 68% were susceptible to tobramycin. There were 95 strains which could be evaluated for synergistic killing by the antimicrobial combinations. Synergism was shown against 78% of strains by cefotaxime and amikacin, against 71% by cefotaxime and tobramycin and against 64% by cefotaxime and gentamicin. In 19 of 22 instances where a bacterial strain was resistant to both cefotaxime and the aminoglycoside, synergistic killing with clinically achievable levels of both antimicrobial agents was demonstrated. There was no significant decrease in concentration of any of the three aminoglycosides after incubation with cefotaxime at 37 degrees C for 0, 4 or 24 h.

Aminoglycosides

Elevated serum D-arabinitol levels in patients with sarcoidosis.

D-Arabinitol has been found in the serum of patients with candidiasis in an incidence varying from 38 to 82%. While screening serum by gas chromatography for the presence of this sugar, we observed elevated concentrations in several patients with sarcoidosis. In an attempt to determine the significance of this chance observation, we tested serum from additional patients with sarcoidosis along with serum from patients with other clinical conditions known to be associated with elevated D-arabinitol levels. Of 53 patients with sarcoidosis, 27 (51%) had elevated concentrations of this compound. Only one of these patients had decreased renal function (creatinine, 2.5 mg/dl). We were unable to correlate elevated values with extent of the disease. Although the significance of this finding is not clear, it may represent a clue to the pathogenesis of sarcoidosis.

Adolescent

Prosthetic valve endocarditis.

Fifty-three (3.6%; actuarially 4.1% at 48 months) of 1465 consecutive in-hospital survivors of valve replacement from 1975 to July 1979 (aortic, mitral, or aortic and mitral, only one untraced) developed prosthetic valve endocarditis (PVE). Incremental risk factors for developing PVE were native valve endocarditis (p less than .0001), black race (p = .0001), mechanical prosthesis (vs bioprosthesis) (p = .005), male sex (p = .04), and longer cardiopulmonary bypass time (p = .09). In general, the hazard function for developing PVE was greatest at 3 weeks after valve replacement. Patients with native valve endocarditis had a tendency to develop PVE early after valve replacement, as did patients in whom mechanical prostheses were used. PVE associated with Staphylococcus epidermidis tended to appear within 6 months of valve replacement, whereas streptococcal PVE tended to appear later after valve replacement. PVE took an atypical form in some patients, but patients with possible PVE (n = 6) had the same findings as those with certain PVE (n = 47). In 11 patients bacteriologic confirmation of PVE was not obtained. The typical prosthetic and periprosthetic characteristics of PVE were present in 30 of the 40 cases in which observations were possible. PVE is a serious condition; 34 (64%) of our 53 patients died. Most deaths occurred within 3 months of the first evidence of PVE. Recovery of some patients is possible with appropriate medical and surgical treatment, but more intense preventive measures are indicated.

Endocarditis, Bacterial