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Biomedical subjects

M I Marks

Publications and source records attributed to M I Marks.

At least 109 records · Page 6Linked to original sources

Activities of various beta-lactams and aminoglycosides, alone and in combination, against isolates of Pseudomonas aeruginosa from patients with cystic fibrosis.

The inhibitory and bactericidal activities of carbenicillin, ticarcillin, moxalactam, cefoperazone, azlocillin, piperacillin, ceftazidime, and three aminoglycosides, alone and in various combinations, were determined against 60 isolates of Pseudomonas aeruginosa from the sputum of patients with cystic fibrosis. Ceftazidime was the most active beta-lactam, with minimum inhibitory and bactericidal concentrations for 90% of isolates of 4 micrograms/ml. Moxalactam was the least active of the new beta-lactams, with activity equivalent to that of carbenicillin; each had a minimum inhibitory concentration for 90% of isolates of 64 micrograms/ml and a minimum bactericidal concentration for 90% of isolates of 128 microgram/ml. All combinations of an aminoglycoside plus a beta-lactam showed favorable inhibitory effects. Combinations of beta-lactams showed mostly addition or indifference. Although little antagonism was seen with combinations of beta-lactams or with aminoglycoside-beta-lactam combinations, no consistent advantage of beta-lactam combinations was demonstrated in vitro. These results suggest several single drugs and combinations that merit clinical evaluation in cystic fibrosis patients with Pseudomonas pulmonary infections.

Amikacin↗

In vitro activity of antibiotics commonly used in the treatment of otitis media against Streptococcus pneumoniae isolates with different susceptibilities to penicillin.

Susceptibilities of 82 clinical isolates of Streptococcus pneumoniae, including 25 from the middle-ear fluid, were evaluated against antibiotics commonly used in the treatment of acute otitis media. Potentially significant resistance occurred in 6% of the isolates to erythromycin and an erythromycin-sulfisoxazole combination. The combination of trimethoprim and sulfamethoxazole was synergistic for 95% of the isolates. Only 2.5% of all of the isolates were resistant to both erythromycin-sulfisoxazole and trimethoprim-sulfamethoxazole. The presently used drug regimens should be effective against the majority of S. pneumoniae isolates in otitis media.

Anti-Bacterial Agents↗

In vitro activity of moxalactam and cefoperazone against Streptococcus pneumoniae with differing susceptibilities to penicillin.

In vitro studies were performed to examine the potential usefulness of two new drugs, moxalactam and cefoperazone, for the treatment of infections caused by Streptococcus pneumoniae. 34 isolates of S. pneumoniae with differing susceptibilities to penicillin were examined by disk diffusion, agar and microbroth dilution methods. Isolates highly resistant to penicillin (MIC greater then 1 microgram/ml) were also resistant to moxalactam (MIC = 128 micrograms/ml) but were sensitive to cefoperazone (MIC = 2--4 micrograms/ml). All isolates relatively resistant to penicillin (MIC 0.25--0.5 micrograms/ml) were sensitive to cefoperazone (MIC 0.25--1 microgram/ml) and had moxalactam MICs of 4--16 micrograms/ml for 10/12 isolates. The disk diffusion test was unreliable for detecting strain relatively resistant to moxalactam. These studies showed that cefoperazone is more active than moxalactam in vitro against S. pneumoniae regardless of the penicillin susceptibility of these bacteria.

Cefoperazone↗

Induction of immunity against lethal Haemophilus influenzae type b infection by Escherichia coli core lipopolysaccharide.

Efforts to prevent Haemophilus influenzae type b (HIB) infections in infancy have been hampered by the low immunogenicity of capsular polysaccharide vaccines in children younger than 18 mos. In searching for alternate immunogens, we have studied the protective potential of polysaccharide-poor, lipid-rich endotoxin (LPS) core in experimental HIB infections. Because all gram-negative bacteria have similar LPS core structures, we were able to use as vaccine the J5 mutant of Escherichia coli 0111, the LPS of which consists only of core components, and thus to avoid problems in interpretation arising from vaccine contamination with non-LPS HIB immunogens. Mice were given graded inocula of HIB and developed lethal infection analogous to human HIB disease when virulence was enhanced with mucin and hemoglobin. After active immunization with heat-killed E. coli J5, 40/50 (80%) of infected mice survived, compared with 14/50 (28%) of saline-immunized controls (P less than 0.005). Passive immunization with rabbit antiserum against E. coli J5 prevented lethal HIB infection when administered 24 or 72 h before or 3 h after infection. This protection was abolished by adsorption of antiserum with purified J5 LPS, with survival reduced from 14/24 to 0/24 (P less than 0.005). Furthermore, rabbit antiserum to purified J5 LPS gave just as potent protection against death as antiserum to whole J5 cells. These studies demonstrate that immunity to core LPS confers protection against experimental murine HIB infection and provide the framework for a new approach to prevention of human disease from HIB.

Antibody Formation↗

Pediatric nocardiosis.

Characteristics of Nocardia infection, which occurred in ten Oklahoma children between 1975 and 1980, are described. Fatal N asteroides infection occurred in three immunocompromised patients. Pneumonia was the presenting feature in each; one patient had disseminated disease. The first reported case of shunt-associated N asteroides ventriculitis occurred in a 2-month-old girl, who was successfully treated with oral trimethoprim-sulfamethoxazole. N brasiliensis was isolated from six immunologically competent children, five of whom had localized, uncomplicated, cutaneous infections. The sixth child developed osteomyelitis following a compound skull fracture. Based on this experience and a review of the literature, N asteroides infections are associated with immunocompromised hosts, and usually are seen as pneumonia with occasional dissemination to other sites. In contrast, N brasiliensis infections are more common than previously thought and usually occur in otherwise normal children as acute posttraumatic pyoderma.

Adolescent↗

Oral chloramphenicol in the treatment of Haemophilus influenzae meningitis.

We conducted a prospective, randomized evaluation of oral chloramphenicol administration for completion of therapy of Haemophilus influenza type b meningitis in 44 children: 21 received drug by this route after the second day of therapy, the remainder continued to receive the drug intravenously. Resolution of clinical manifestations and cerebrospinal fluid indicators of meningitis was equivalent with both routes in 43 patients. One infant failed to achieve efficacious serum concentrations by either route of administration. Paired analysis of the area under the serum concentration versus time curve in 13 patients after oral and intravenous administration indicated equivalent bioavailability. Neutropenia was the only observed drug-related toxicity and correlated with the highest observed serum concentration. We conclude that: (1) chloramphenicol can be used by the oral route to complete treatment of H. influenzae type b meningitis; (2) a dose of 75 mg/kg/day is effective and less likely than higher doses to cause neutropenia; and (3) the measurement of serum chloramphenicol concentrations is important, regardless of route of administration.

Administration, Oral↗

Susceptibility of group A beta-hemolytic Streptococcus isolates to penicillin and erythromycin.

We have reevaluated the antibiotic susceptibilities of group A beta-hemolytic streptococci in view of recent reports of a high prevalence of erythromycin resistance in Japan and of an increase in penicillin treatment failures in the United States. A total of 474 isolates recovered during a 2- to 3-month period in 1980 were tested. All were susceptible by microtiter broth dilution to a penicillin concentration of less than or equal to 0.03 micrograms/ml (minimal inhibitory concentration), and 473 were killed by less than or equal to 0.06 micrograms/ml (minimal inhibitory concentration). Erythromycin minimal inhibitory concentrations showed a bimodal distribution: 95% were less than or equal to 0.06 micrograms/ml, and 5% were greater than or equal to 1 microgram/ml. Of the minimal bactericidal concentrations, 21% were greater than or equal to 1 microgram/ml and 3% were greater than or equal to 16 micrograms/ml. Group A beta-hemolytic streptococci remain susceptible to the inhibitory and bactericidal actions of penicillin, thus providing no in vitro explanation for the bacteriological relapses reported in some clinical studies. Unlike the Japanese experience, only 5% of our isolates were resistant to erythromycin (minimal inhibitory concentration, greater than or equal to 1 microgram/ml); however, 22% were tolerant (ratio of minimal inhibitory/bactericidal concentrations, greater than or equal to 32).

Erythromycin↗

New concepts in viral gastroenteritis.

The use of negative contrast electronmicroscopy of stool suspension in the investigation of the aetiology of childhood gastroenteritis has led to the recognition of a number of candidate viral agents. There is convincing evidence that rotavirus is the single most important cause of community acquired gastroenteritis, and is responsible for some nosocomial outbreaks. The epidemiology of rotavirus acqusition, differential clinical susceptibilities of young and older infants, pathogenesis of disease, mechanisms of immunity and breast milk protection, and the role of different viral serotypes are aspects as yet poorly understood; and attempts to propagate human rotavirus in tissue culture have met with only limited success. Moreover, the aetiologically unaccountable one third of cases of infantile diarrhoea, and the association of enteritis with up to six other virus-like particles add to the complexity of the problem. This review considers the available data from human and animal studies, and based on the experience of ourselves and others comments on the present state of knowledge and trends in continuing research.

Diarrhea, Infantile↗