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Biomedical subjects

M B Pasticci

Publications and source records attributed to M B Pasticci.

At least 19 recordsLinked to original sources

Treatment of post-traumatic hand Staphylococcus aureus osteomyelitis with oral linezolid.

The Authors report on the use of linezolid for the treatment of three patients with osteomyelitis. All three patients had post-traumatic multisensitive hand bone methicillin-susceptible Staphylococcus aureus osteomyelitis, which did not respond to antimicrobial regimens including drugs in vitro active against the isolated strains. Clinical cure and microbiologic eradication was obtained with oral linezolid in all three patients. Linezolid was well tolerated. Mild thrombocytopenia was observed in one patient at the end of the third week of treatment and it was promptly resolved after the discontinuation of linezolid. Linezolid minimum inhibitory concentrations (MICs) consisted of 2 mg/l for all three S. aureus isolates while the bactericidal activity in vitro was not present up to the linezolid concentration of 32 mg/l. In spite of a lack of in vitro bactericidal activity, linezolid was effective in curing the patients and eradicating the infection. Trough and peak plasma concentrations of linezolid were above the MICs of the isolates. These values ranged from 3.93 to 14.95 mg/l at trough and 5.03 to 25.91 mg/l at peak. The oral bioavailability, pharmacokinetic profile and antibacterial spectrum of linezolid make this oxazolidonone antimicrobial an attractive drug for the treatment of chronic osteomyelitis. Prolonged administration requires careful surveillance for side effects, until these complications are better understood.

Acetamides↗

Clinical efficacy and tolerability of caspofungin in a renal transplant patient with Aspergillus flavus lung infection: case report.

Organ transplant recipients are at increased risk for severe invasive aspergillosis, and amphotericin deoxycholate has been the standard treatment for many years. Currently, however, lipid formulations are preferred due to their few side effects. Also, a number of new antifungal drugs have been developed including new azoles and echinocandins. Caspofungin is the first of the echinocandin derivatives patented to treat patients with invasive aspergillosis who are refractory or intolerant to other therapies. A renal transplant patient on immunosuppressive treatment with chronic hepatitis B virus infection was admitted with fever, hemophthisis and lung consolidation, diagnosed to be probably caused by Aspergillus flavus. The patient developed cholestatic hepatitis most likely related to itraconazole. Clinical failure and in vitro itraconazole resistance of the isolate was also documented while the patient was receiving itraconazole at a reduced dosage. Caspofungin was administered once a day as ambulatory treatment and was well tolerated. Clinical improvement was observed after 6 weeks of treatment and no hepatic toxicity was documented. Caspofungin seems to be a potentially useful antifungal agent in renal transplant patients with invasive aspergillosis. Further evaluation of the efficacy of caspofungin is needed.

Antifungal Agents↗

Fluconazole susceptibility and strain variation of Candida albicans isolates from HIV-infected patients with oropharyngeal candidosis.

Over a 16 month period we conducted a prospective study in a cohort of 45 HIV-positive patients to detect the development of resistance to fluconazole and to analyse the epidemiology of oropharyngeal candidosis (OPC). Each episode was treated with fluconazole 100 mg/day po for 10 days. All yeast isolates were tested for their in-vitro susceptibility to fluconazole. Multiple strains of Candida albicans simultaneously isolated from a given patient were typed by electrophoretic karyotyping. Overall, 106 episodes of OPC were diagnosed among the 45 patients: 18/45 patients (40%) had only one episode, 11/45 (24%) had two episodes, and the remaining 16/45 (36%) had three or more episodes (range 3-7). Cure (complete resolution of signs and symptoms and negative post-treatment cultures) and improvement (complete resolution of signs and symptoms but positive post-treatment cultures) were observed in 30/106 (28%) and 69/106 (65%) episodes of OPC, respectively. Failure (absence of improvement or exacerbation of signs and symptoms) was observed in seven episodes (7%) from four patients. In two of these four patients a significant and progressive increase in fluconazole MICs was observed: from 0.25 to 16 mg/L in one patient, and from < or = 0.125 to 32 mg/L in the second one. Tests on multiple colonies from individual isolation plates showed that it was not unusual to obtain different fluconazole MICs, indicating that, in order to avoid misleading results, one should perform in-vitro susceptibility testing by using a multiple colony inoculum rather than an inoculum made from a single colony. A total of 213 strains of C. albicans isolated from seven patients who suffered from four or more episodes of OPC through the course of the study were typed by electrophoretic karyotyping. Five individuals (71%) were infected with yeasts with only one DNA type, while the other two patients showed the presence of two or three different DNA types. The simultaneous presence of multiple types was found only in one of the seven subjects. Our data confirm the efficacy of fluconazole 100 mg/day for the treatment of OPC in HIV patients. Isolation of fluconazole-resistant strains of C. albicans with this regimen is rare. The vast majority of HIV patients are infected with a unique strain of C. albicans throughout each episode of infection. A minority of patients, however, can harbour strains of C. albicans with variable patterns of fluconazole susceptibility simultaneously.

AIDS-Related Opportunistic Infections↗

[Susceptibility of P. aeruginosa and enterobacteriaceae isolated from 1986 to 1994 in the Microbiology laboratory of the Infectious Diseases Institute of Perugia University].

From 1986 to 1994, 812 P. aeruginosa, 1997 E. coli, 437 P. mirabilis, 400 Klebsiella spp., 238 Enterobacter spp., 130 Serratia spp. strains were isolated from clinical materials in the Microbiology laboratory of the Infectious Diseases Institute of Policlinico Monteluce, Perugia University. During the study period the Authors observed the following variations in the susceptibility patterns: increased resistance of P. aeruginosa to piperacillin from 20.8% to 27.2% (P<0.05), amikacin from 11.9% to 17.5% (P<0.05), netilmicin from 11.8% to 28.6% (P<0.01), pefloxacin from 74.4% to 87.8% (P<0.01); E. coli to norfloxacin, ciprofloxacin and pefloxacin, respectively from 1.3% to 3.6% (P<0.001), from 1.5% to 3.6% (P<0.05) and from 3.2% to 9% (P<0.001); Serratia spp. to ceftazidime from 14% to 33.3% (P<0.05); Enterobacter spp. to norfloxacin from 5.1% to 13.6% (P<0.05), cotrimoxazole from 12.8% to 23.5% (P<0.05) and chloramphenicol from 19.4% to 31.8% (P<0.05). Moreover cephalotin resistant strains of E. coli decreased from 29.3% to 21.3% in the last 4 years (P<0.001).

English Abstract↗

Ceftriaxone versus imipenem/cilastatin as empirical monotherapy for infections in cancer patients.

We conducted a prospective randomized clinical trial to compare the efficacy and tolerability of monotherapy with ceftriaxone (active ingredient of Rocephin) (CRO) versus imipenem/cilastatin (I/C) in febrile cancer patients with or without neutropenia. 120 febrile episodes were randomized and 89 (75%) were evaluable for efficacy analysis. The overall response rates to both regimens were good (86 and 79% improved in response to CRO and I/C, respectively). Overall mortality was low and similar in the two groups. Both regimens were well tolerated. Our preliminary data corroborate the efficacy of CRO or I/C as empirical monotherapy for febrile episodes in cancer patients. It will be up to future investigations to show whether one of these regimens is superior to the other.

Adult↗

Susceptibility of gram positive cocci to teicoplanin. Three year survey (1984-1986) at Perugia University.

From 1984 to 1986, 1038 Gram positive cocci (865 Staphylococci and 173 Enterococci) have been tested for sensitivity to teicoplanin by the agar diffusion method: only one strain (Staphylococcus haemolyticus) resulted to have no zone of inhibition around the teicoplanin disk. All Staphylococcus haemolyticus strains showed higher MIC: 2.79 mcg/ml after 24h of incubation and 20.50 mcg/ml after 48h. The reduced teicoplanin sensitivity of Staphylococcus haemolyticus was not detected by the agar diffusion test.

Anti-Bacterial Agents↗

Technical factors influencing the bactericidal activity of teicoplanin against staphylococci.

Considering 99.9% Killing after 24h of incubation, mean bactericidal activity of teicoplanin against 48 clinical isolates of Staphylococci resulted to be 67.7 micrograms/ml. Fortyfour out of 48 strains (91.7%) resulted tolerant. The high percentage of tolerant was dependent on survivors above the 0.1% allowed in several tube dilutions. Prolonged incubation consistently reduced this number. Only 37.5% of our strains remained tolerant after 48h of incubation. Bactericidal activity of teicoplanin was also significantly influenced by other technical factors. Human serum enhanced the killing of teicoplanin. For 9 strains of Staphylococcus aureus geometric mean MBC decreased from 49.9 muug/ml to 3.9 micrograms/ml (p less than 0.05); also actively growing bacteria demonstrated a higher killing rate, resulting in lower MBCs (mean 3.8 micrograms/ml). Micromethod technique was greatly influenced by the carryover phenomenon. The spot subculture technique is not accurate for bactericidal studies. A standardized technique for determining the minimal bactericidal activity is needed.

Anti-Bacterial Agents↗

Killing rate and serum bactericidal activity of oxacillin, rifampin and ciprofloxacin against Staphylococcus aureus.

The bacterial activity of oxacillin, rifampin and ciprofloxacin was examined at two concentrations by the serum bactericidal rate (SBR) technique against 5 strains of methicillin-susceptible Staphylococcus aureus. The activity of oxacillin plus ciprofloxacin and oxacillin plus rifampin was also determined for 5 strains of staphylococci examining in vitro the SBR and the serum bactericidal activity (SBA). We simulated SBR and SBA in vitro using pooled human serum containing know concentrations of antimicrobial agents. The rate at which the antibiotics kill S. aureus did not rise by increasing the concentrations over the MBC. The oxacillin-ciprofloxacin combination was indifferent when tested by the rate of killing, whereas an antagonistic interaction was frequently observed with the oxacillin-rifampin combination. The SBA was determined by two methods: the technique of the Mayo Clinic that uses Mueller-Hinton broth (MHB) as the diluent and the method of Stratton in which the diluent was prepared with MHB supplemented with Ca++ and Mg++ and combined with 50% pooled human serum. The activities of oxacillin and rifampin were decreased in the presence of human serum. These results were attributed to the high protein binding of these antibiotics. Rifampin in combination with oxacillin showed antagonism against S. aureus also by the SBA method. The inhibitory activity of drugs in combination remained substantially the same as the single more active one.

Ciprofloxacin↗

Imipenem/cilastatin in the treatment of severe hospital infections.

Imipenem/cilastatin as a single agent or in combination with amikacin was used as empirical treatment of severe hospital infections. Twenty-five patients were evaluable for efficacy and the overall response rate was 62% with imipenem/cilastatin alone and 80% with imipenem/cilastatin in combination with amikacin. The highest response rate was obtained in urinary tract infection (75%) and in pneumonia (70%) and the lowest response rate (50%) was observed in bacteremia of unknown origin and in skin and soft tissue infections. Eight failures were observed and seven of them occurred in patients treated with imipenem/cilastatin alone. Two deaths occurred, both in patients with bacteremia. Imipenem/cilastatin treatment was interrupted early in 3 patients because the pathogen developed resistance during therapy and in 2 other patients because of side effects. In our study imipenem/cilastatin proved to be efficacious and well tolerated. The addition of an aminoglycoside to imipenem/cilastatin might improve its efficacy and prevent pathogens from becoming resistant during therapy. Therefore this association would seem to be advisable for the therapy of bacteremic infections and for those caused by difficult pathogens.

Adult↗

Treatment of infections by staphylococci and other gram-positive bacteria with teicoplanin: an open study.

Teicoplanin, 200-400 mg (3-6 mg/kg) daily iv or im, was used to treat 71 episodes of infection. The average duration of treatment was 22 days. The 64 evaluable episodes comprised 24 skin/soft tissue, 20 osteoarticular, ten urinary tract and one ventriculo-atrial shunt infections; one case of primary bacteraemia, three of endocarditis, two of pneumonia and three of pleural empyema. Fifty-five episodes were treated with teicoplanin monotherapy and nine with teicoplanin in association to other antibiotics. Overall 61% (39/64) of the evaluable infections were cured, 25% (16/64) improved and 14% (9/64) failed. Staphylococcus aureus was the most frequent pathogen, with 46 isolates. Infections by both methicillin-sensitive and resistant Staph. aureus strains showed favourable clinical and microbiological responses to teicoplanin. Side effects were observed in eight of the 64 episodes (12.5%). Bronchospasm was observed in two other cases at the beginning of therapy and the antibiotic administration was discontinued. Teicoplanin is an effective and well tolerated antibiotic for infections by Gram-positive bacteria, and it is effective against methicillin-resistant staphylococci.

Adolescent↗