Infectious complications in experimental small bowel transplantation.
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Biomedical subjects
Publications and source records attributed to P Marone.
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We compared the in vitro activity of daptomycin, a new lipopeptide antibiotic, with that of vancomycin and other selected agents against 95 coagulase negative staphylococci (CNS) isolates causing septicemia or foreign-body infections in immunocompromised patients. These strains were classified as follows: 51 methicillin-susceptible CNS (23 slime producers); 44 methicillin-resistant CNS (23 slime producers). We also investigated the activity of daptomycin against 50 Enterococcus faecalis isolates. Minimal inhibitory concentrations (MICs) were determined by the broth microdilution method. Daptomycin at a concentration of 2 mg/L was inhibitory for all the evaluated strains. Vancomycin and ciprofloxacin showed good activity: 90% of the strains were inhibited by these agents at 8 mg/L. The activity of netilmicin, rifampin and trimethoprim-sulfamethoxazole was instead limited. Resistance to the antimicrobial agents tested was seen with increased frequency among slime producing strains. Daptomycin and teicoplanin were the most active agents tested against E. faecalis (MIC90 0.25 mg/L and 0.12 mg/L).
The adherence of Bordetella pertussis to respiratory cilia and its survival in neutrophils and macrophages is crucial to the pathogenesis of whooping cough. To investigate the role of endogenous interferon (IFN)-gamma in acute infection, levels of IFN-gamma in bronchoalveolar lavage (BAL) fluid of mice infected intranasally with B. pertussis were determined. Since pertussis toxin is released during infection by B. pertussis either locally or systemically, serum levels of IFN-gamma in mice injected intravenously with pertussis toxin were also determined. A persistent and significant increase of IFN-gamma levels with concomitant peripheral blood lymphocytosis was observed after 5 and 10 days. The results of this study showed an early but transitory production of endogenous IFN-gamma in BAL fluid of mice infected with B. pertussis.
A combination of clarithromycin, ciprofloxacin, and amikacin for the treatment of Mycobacterium avium-Mycobacterium intracellulare bacteremia was evaluated in 12 AIDS patients. Mycobacteremia cleared in all patients by 2 to 8 weeks of treatment, and symptoms resolved. Four patients died; all had negative blood cultures until death, and disseminated M. avium-M. intracellulare complex infection was not considered the primary cause of death.
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The use of teicoplanin was evaluated in a group of 33 patients, which included 18 prosthetic infections, seven with osteomyelitis, five skin and soft tissue infections, and three cases of septic arthritis. The bacterial pathogens isolated were 27 isolates of Staphylococcus aureus (methicillin sensitive 18; methicillin resistant 9), Staph. hominis (2), Staph. epidermidis (1), Staph. haemolyticus (2), Enterococcus faecalis (1), Streptococcus pyogenes (1), Peptococcus spp. (1). Eleven patients had polymicrobial infections (Gram-positive plus Gram-negative and/or anaerobic bacteria). In ten cases (nine polymicrobial infections) teicoplanin was used in combination with other antibiotics. Teicoplanin was administered intravenously 400 mg every 24 h in 26 cases, 200 mg every 24 h in six cases and 600 mg every 24 h in one case. The duration of the treatment ranged from 9 to 73 days with a mean of 27.3. Efficacy was evaluable in 30 patients, because in three patients treatment was stopped because of adverse reactions. Cure or improvement was noted in 28 patients (93%). Bacteriological cure occurred in 25 patients (83.3%).
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Synergy between cefotaxime and desacetyl-cefotaxime was evaluated against 12 strains (9 Enterobacteriaceae and 3 Bacteroides fragilis) by the chequerboard technique. A 1:1 combination of cefotaxime and desacetyl-cefotaxime was synergistic against two-thirds of the 12 strains tested. The in vitro activity of the combination was compared with that of four other beta-lactam antibiotics against 96 recent clinical isolates: 78 Enterobacteriaceae, 8 Haemophilus influenzae, 10 B. fragilis. The MICs of the combination for Gram-negative bacilli were similar to those of ceftazidime. Cefotaxime/desacetyl-cefotaxime was more active than cefotetan, cefonicid and piperacillin against Enterobacteriaceae and H. influenzae.
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Recent evidence would suggest that HTLV-III may be neurotropic. We have found oligoclonal IgG bands by isoelectric focusing in the CSF of a homosexual man with AIDS and encephalitis. Subsequent analysis revealed that such bands contained anti-HTLV-III activity, suggesting that neurologic symptoms in AIDS patients may be caused by replication of HTLV-III inside the CNS.
In this study we report about the efficacy and tolerability of ofloxacin in the treatment of 15 patients with severe and moderately severe infections including osteomyelitis (5), soft tissue infections (5), salmonellosis in AIDS patients (2), acute or chronic pulmonary infections (2) and mediastinitis (1). The following organisms were isolated in culture specimens: Staphylococcus aureus (4), Pseudomonas aeruginosa (4), Staphylococcus epidermidis (3), Serratia marcescens (1), Escherichia coli (1), Aeromonas hydrophila (1), Klebsiella oxytoca (1), Klebsiella pneumoniae (1), Salmonella cholerae-suis (1), Salmonella sp. (1), Enterobacter cloacae (1). All isolates were sensitive to the drug. Of 5 cases with osteomyelitis, 2 were cured and 3 improved clinically (with bacteriological eradication of the pathogens). The best results were obtained in patients with soft tissue infections: 4 patients were cured and 1 improved. Two patients with salmonella bacteremia and AIDS experienced a recurrence 1 month and 2 months respectively after stopping therapy. The patient with mediastinitis was successfully treated. Improvement was recorded for 2 patients with bronchiectasis and exacerbation of chronic bronchitis. The drug was well tolerated, only one episode of mild nausea and vomiting was reported and did not require discontinuation of the therapy. The study indicates that ofloxacin is a safe and effective agent in the treatment of various infections.
The in vitro activity of antibiotic combination of teicoplanin and gentamicin (or netilmicin) and teicoplanin and cephalotin on Staphylococcus aureus was evaluated using the checkerboard method and time-kill curves. With few exceptions neither antagonism nor synergism was seen for the combination of teicoplanin and aminoglycosides using the checkerboard method. Using time-kill curves synergism was often found for the combination of teicoplanin and netilmicin (even at sub-minimal inhibitory concentrations of netilmicin) and for the combination of teicoplanin and cephalotin. No antagonistic interactions occurred.
Two cases of unsuspected Strongyloides stercoralis infection were elucidated by the displacement of bacterial colonies on primary plating media. Observation of primary plates inoculated for the diagnosis of bacterial pneumonia or gastroenteritis revealed that normal flora colonies had been moved and were aligned in a pathway, or track. This unusual colony alignment prompted us to request a stool for the examination of parasites, and S. stercoralis was found. It was concluded that the parasite is capable of motility on agar surfaces, resulting in the displacement of bacterial colonies that make up the normal flora.
The kinetics of RV11 (propionyl erythromycin mercaptosuccinate) in serum and bronchial secretions was investigated in heterogeneous bronchopneumopathic patients requiring diagnostic bronchoscopy. A single oral dose, equivalent to 500 mg of erythromycin base, was administered to all patients and the bronchial secretion and plasma concentrations were determined after 2, 3 and 4 hr. The bronchial secretion and plasma levels consistently exceeded those reported previously for erythromycin per os, suggesting that RV11 may have an unusually high affinity for bronchial secretions in humans. The results of this study also suggested that RV11 might have different kinetics in bronchial secretions and serum, though further studies are required to provide definitive evidence.
Resistance of Enterobacter, Serratia and pseudomonas strains to newer cephalosporins is often associated with stable derepression of synthesis of the chromosomal betalactamases. Similar resistance is developed by enzyme inducible strains in response to betalactamases inducers. This finding poses many clinical problems including emergence of resistance during therapy with the drugs. In this study we evaluated the MICs of several new betalactam compounds against 76 Enterobacter, Serratia and Pseudomonas strains before and after cefoxitin-induction of betalactamases. The MICs against several Enterobacter strains (45%) after cefoxitin induction were elevated four fold or more. Serratia strains showed no significant variations of the MICs after cefoxitin induction. The MICs of piperacillin against many Pseudomonas strains (78%) after cefoxitin induction were elevated four fold or more. These data were confirmed using cefoxitin disk approximation test. Outbreaks of nosocominal infection with these multiresistant bacteria and spread of the strains throughout the hospital are already being seen. Control of these problems can only be achieved through the judicious and restricted use of these new antibiotics.
In this study we have evaluated the bactericidal activity kinetics of some cephalosporins, ureidopenicillins and aminoglycosides against 41 gram negative clinical isolates. Aminoglycosides, particularly gentamicin, showed the better bactericidal activity which appeared already at the second-third hour after the addition of the antibiotic. The bactericidal activity of cefotaxime, ceftazidime and cefotetan was remarkable but it appeared only at the sixth-eight hour. This difference was statistically significant. Carbenicillin and piperacillin showed a low bactericidal activity against Pseudomonas aeruginosa. We noted a wide variability of the antibiotic bactericidal activity against the isolates of the same bacterial species. Therefore we can argue that in serious infections the determination of the antibiotic and serum bactericidal activity is necessary.
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In this study we report about the efficacy and tolerability of ceftazidime in the treatment of 10 cases of pseudomonal meningitis (nine Pseudomonas aeruginosa and one Pseudomonas cepacia). The 10 patients had a pseudomonal infection of the central nervous system (CNS) complicating neurosurgical procedures or developed on a preexisting immunodepressing condition; four patients were of pediatric age. All isolates were sensitive to ceftazidime with MICs ranging from 0.39 to 3.12 micrograms/ml. Ceftazidime was given intravenously at the dosage of 100-150 mg/kg/day. In seven cases amikacin was associated by intralumbar or intraventricular instillation. The duration of ceftazidime treatment ranged from 9 to 49 days with a mean of 22.2. Eight cases out of ten were cured bacteriologically and clinically, while the remaining two were cured after treatment with other antibiotics. Concentrations of ceftazidime in serum and in lumbar and/or ventricular cerebrospinal fluid (CSF) were obtained in four cases; the mean concentration in lumbar CSF was 12.2 micrograms/ml and in ventricular 3.3 micrograms/ml. The study demonstrated that ceftazidime is effective in the treatment of Pseudomonal meningitis.