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Biomedical subjects

R Yogev

Publications and source records attributed to R Yogev.

At least 109 records · Page 6Linked to original sources

In vitro interaction between rifampin and clindamycin against pathogenic coagulase-negative staphylococci.

The MICs and MBCs for 90% of strains tested (MIC90 and MBC90, respectively) of rifampin for 75 clinical isolates of pathogenic coagulase-negative staphylococci (PCNS) were 0.03 and 0.25 microgram/ml, respectively, while the MIC90 and MBC90 of clindamycin were both greater than 25 micrograms/ml. Although no synergy between rifampicin and clindamycin was found among the 15 strains studied by the checkerboard method, 6 of 12 selected strains showed synergy by the kill-curve method. No antagonism was observed by either method. All 30 strains rapidly developed resistance to rifampin in vitro, and this could be prevented by the simultaneous presence of 1.0 microgram of clindamycin per ml in the 24 methicillin-susceptible PCNS strains. The synergy between rifampin and clindamycin observed in vitro for some strains of PCNS, together with the prevention of emergence of resistance to rifampin by clindamycin, suggests that this antibiotic combination may be useful for the treatment of infections caused by methicillin-susceptible PCNS.

Clindamycin↗

Spiramycin alone and in combination with trimethoprim against Haemophilus influenzae.

Following determination of MICs and MBCs of spiramycin and trimethoprim by the broth microdilution method for 16 typable (including 13 type b) and 15 nontypable H. influenzae isolates, bactericidal synergy was tested by the chequerboard method and the time-kill curve methods. Nineteen (13 typable and six nontypable) of 31 strains demonstrated synergy by the chequerboard method. Ten strains showed indifference, and two manifested antagonism. In contrast, 12/13 strains tested by the time-kill method showed synergy and 1/13 demonstrated indifference. Of note was the finding that seven isolates that showed indifference by chequerboard method (three typable, four nontypable) manifested synergism by the kill-curve method. Of the two nontypable strains showing antagonism by chequerboard, one manifested synergy and the other indifference by the time-kill method. Our studies show that in-vitro synergy between spiramycin and trimethoprim against H. influenzae strains is frequently demonstrable. In-vivo studies may be helpful in confirming these in-vitro observations.

Drug Therapy, Combination↗

Pediatric cerebral abscess.

Fifty-four consecutive cases of children with cerebral abscess from 1958 to 1987 are reviewed. Their average age was 6.6 years, ranging from 3 days to 19 years. A wide range of organisms and underlying diseases was encountered. The predominant mode of surgical therapy was craniotomy with resection of the abscess. Aspiration and craniotomy with drainage-evacuation were also employed in our series. No underlying disease was found in 10 (19%) of the children. Cyanotic heart disease (CHD) was present in 13 (24%) of the children. Four children had dental abscesses and 1 had otitis media. Seven (13%) children had abscesses secondary to hydrocephalus/shunt infections. Sinusitis and otitis accounted for 5 cases (9%). Four children (7%) had tuberculomas. One abscess was associated with a nasal dermal sinus and one was congenital. Fourteen (26%) patients had negative cultures. Fourteen (26%) abscesses contained streptococci of various types. Staphylococci were found in only 5 (9%) of the abscesses. The congenital abscess was caused by salmonella. Two abscesses (7%) were fungal. Both of these patients died. Six children (11%) were treated without surgical intervention. Three of them died. Forty-eight children had surgical intervention; 12 underwent aspiration, 14 underwent open evacuation of the abscess, and 22 had abscesses resected. Mortality in the aspiration group was twice that of the evacuation or resection group (17, 7 and 9%), respectively). The factor which correlated best with mortality was the patient's clinical status on admission. The advent of CT scan at our facility improved mortality by facilitating accurate diagnosis and surgical intervention. Overall mortality rates decreased from 31 to 5.7% and surgical mortality fell from 21 to 2.9%.

Adolescent↗

Haemophilus influenzae type b immunization of children with sickle cell diseases.

Haemophilus influenzae type B vaccine is recommended for children 1.5 to 6 years of age with sickle cell anemia, but the adequacy of their response is unknown. A total of 69 children with sickle cell syndromes, 1.5 to 5.6 years of age, were immunized with two vaccines alternatively, single blind. PRP vaccine was given to 36 children and a diphtheria toxoid conjugated vaccine, PRP-D, was given to 36. Coded pre- and postvaccine sera were tested by radioimmunoassay for anti-PRP antibody. The groups did not differ in age distribution or type of sickle hemoglobinopathy. Preexisting antibody levels were low in both vaccine groups; 65% were less than 0.15 microgram/mL. The vaccines were safe but associated with frequent minor reactions. PRP-D gave higher geometric mean titers and mean fold titer increase than PRP in all children (15.58 micrograms/mL [234-fold] v 2.63 micrograms/mL [29-fold]) and in the subgroups 1.5 to 2.5 years of age or with pretiter values less than 0.15 microgram/mL. Titers for 64% of children receiving PRP and 94% receiving PRP-D were greater than or equal to 1.0 microgram/mL. Thus, both vaccines were useful in this population, but PRP-D was more immunogenic. Duration of antibody levels postvaccination, booster responses, and PRP-D immunogenicity in younger children with sickle cell syndromes all require further study.

Antibody Formation↗

Suppurative intracranial complications of upper respiratory tract infections.

Suppurative intracranial complications of respiratory infections are relatively rare in children. These complications occur more often in association with chronic sinusitis and chronic otitis media. Because symptoms and signs of the intracranial complications can be nonspecific, a high index of suspicion by the physician is important for early diagnosis. The routine cerebrospinal fluid examination often does not distinguish between the various complications, and radiologic procedures such as radionuclide brain scan, arteriography and computer-assisted tomographic scan should be used. Computer-assisted tomographic scan is very useful in detecting early complications allowing trial with medical treatment alone. Appropriate selection of antibiotics must be made on the basis of the likely pathogens in the particular setting and the ability of the antibiotic to penetrate the affected area. Appropriate early management of suppurative intracranial complications should result in a favorable outcome.

Brain Abscess↗

Dissociation of virulence and protection from infection by mutant analysis in Haemophilus influenzae type b.

A Haemophilus influenzae type b (Hib) outer membrane protein with an apparent molecular weight of 98,000 (98K) previously has been shown to react with antibodies that protect against experimental Hib disease. A mutant lacking the ability to synthesize this 98K protein was produced by chemical mutagenesis and identified in a colony blot-radioimmunoassay by its failure to react with a 98K protein-specific monoclonal antibody. DNA from this mutant was used to produce a 98K protein-negative transformant of the wild-type parental strain. Comparison of the relative degree of virulence of the parental strain and the 98K protein-negative transformant in an animal model system revealed no differences in the abilities of these two strains to produce bacteremia after intranasal challenge. These results indicate that the Hib surface-exposed 98K outer membrane protein that reacts with protective antibodies plays no detectable role in the expression of virulence by Hib in an animal model system.

Animals↗

Combination antibiotic therapy in pediatrics.

Combinations of beta-lactam and aminoglycoside antibiotics are frequently used in the treatment of pediatric infections. At our institution, amikacin has been the sole aminoglycoside utilized for the past five years. Such regimens are used empirically in specific patient populations to treat the pathogens most likely to be responsible for a symptom complex, e.g., sepsis in the immunocompromised host, pneumonitis in patients with cystic fibrosis, neonatal infections such as sepsis or meningitis, and infections in patients with intestinal perforations. Beta-lactam and aminoglycoside combinations are employed as definitive therapy when synergistic interactions can be predicted, such as in systemic Pseudomonas infections, viridans streptococcal endocarditis, or enterococcal infections. In all of these circumstances, we have utilized amikacin extensively as the sole aminoglycoside, with highly satisfactory results. In vitro antibiotic synergy studies, including those employing aminoglycosides such as amikacin, may be used to predict in vivo antibiotic interactions. However, definitions of in vitro synergy vary with the laboratory method used to evaluate synergy. Furthermore, recent data from our laboratory suggest that the absence of demonstrated in vitro synergy between amikacin and imipenem may not correlate with improved survival of neutropenic rats with gram-negative sepsis that are treated with both agents. Thus, in vitro studies of synergy may underestimate the frequency of improved outcomes with combination antibiotics, especially with amikacin and imipenem. There are potential risks associated with the use of multiple, broad-spectrum antibiotics, including fungal or bacterial superinfection and increased drug toxicity. Although the former is common in pediatric patients, aminoglycoside (amikacin) toxicity has rarely been a problem. Combination antibiotic regimens that include an aminoglycoside such as amikacin continue to have an important role in pediatrics and should be used empirically or definitively for the specific indications discussed.

Amikacin↗

The localization of urinary tract infection with 99mTc glucoheptonate scintigraphy.

A retrospective study was performed of 39 children at the Children's Memorial Hospital, Chicago, Illinois, who underwent technetium-99m glucoheptonate (99mTcGH) scintigraphy for evaluation of possible urinary tract infection. Clinical and laboratory criteria classified the children as having pyelonephritis, cystitis, or no urinary tract infection. Of 28 children classified as having pyelonephritis, 24 (86%) children had abnormalities on 99mTcGH scintigraphy. Only 8 of 19 (42%) renal ultrasound scans and 4 of 17 (24%) intravenous pyelography studies performed in these children demonstrated findings consistent with parenchymal disease. Only 9 of 19 (47%) cystograms demonstrated vesicoureteral reflux. Three children who underwent gallium-67 citrate scintigraphy had localization at the sites of focal defects with 99mTcGH scintigraphy. 99mTcGH scintigraphy is a sensitive and specific indicator of renal parenchymal involvement that helps localize urinary tract infection to the kidney.

Child↗

Correlation of antibiotic synergy in vitro and in vivo: use of an animal model of neutropenic gram-negative sepsis.

The predictive value of in vitro studies of antibiotic interaction for clinical drug interactions is unclear. Five clinical isolates (two Klebsiella, two Pseudomonas aeruginosa, and one Serratia marcescens) were evaluated by the time-kill curve method for in vitro synergy between amikacin and imipenem. When we used the stringent definition of synergy of Hallander et al., no synergy was present for any study strain; however, when we used a more-conventional definition of synergy, these drugs interacted synergistically against all study strains. The results of these in vitro studies were correlated with in vivo interactions by using neutropenic infant rats injected ip with study organisms and given various treatment regimens. For 80% of the study strains, treatment of rats with amikacin and imipenem resulted in significantly greater survival than did therapy with either drug alone or than could be predicted by addition of survival rates achieved with either agent alone (P less than .005). In vitro studies predicted this in vivo synergy in 80% of the cases when the more-conventional definition of synergy was used, whereas they were not predictive when the more-stringent definition of synergy was used. This rat model of neutropenia and gram-negative sepsis may provide more insight into in vivo drug interactions than do current methods.

Agranulocytosis↗

In vitro activity of antibiotics alone and in combination against Actinobacillus actinomycetemcomitans.

The MICs for 90% of the organisms tested (MIC90S) of 11 antibiotics against 24 clinical isolates of Actinobacillus actinomycetemcomitans were determined by the MIC 2000 system. The lowest MIC90S (16 micrograms/ml) were observed with ceftriaxone and rifampin. The next lowest MIC90S were found with cephapirin, tetracycline, and chloramphenicol (3.12 micrograms/ml). The MIC90S of penicillin, ampicillin, ticarcillin, piperacillin, and amikacin were each greater than or equal to 12.5 micrograms/ml. Antibiotic synergy was studied by the killing curve method and was defined as a greater than or equal to 2 log10 reduction in CFU when two antibiotics were used in combination at one-fourth the MBC for each compared with the effect of each antibiotic alone at one-half the MBC. Synergism between rifampin and penicillin, cephapirin, or ceftriaxone was tested for with 12 A. actinomycetemcomitans strains. In 7 of 37 instances, synergism was demonstrated for the combinations rifampin plus ceftriaxone (n = 3) or rifampin plus penicillin (n = 4); in 9 instances, an additive effect was noted, and impaired killing with drug combinations compared with the effect of a single antibiotic was suggested in 4 strains. The majority of strains were indifferent to the combinations. Similarly, variable results were observed when the combination of trimethoprim and cephapirin was tested against eight A. actinomycetemcomitans strains. Our data suggest that rifampin and cephapirin are the most active of the 11 antibiotics studied against A. actinomycetemcomitans. In addition, in vitro synergism between rifampin and other antibiotics or between trimethoprim and cephapirin was not consistently demonstrable.

Actinobacillus↗