Penetration of moxifloxacin into bone in patients undergoing total knee arthroplasty.

OBJECTIVES: To investigate plasma and bone moxifloxacin concentrations following oral administration of a single or double dose of the drug, in order to consider its potential role in the treatment of osteomyelitis. PATIENTS AND METHODS: Thirty consecutive patients undergoing total knee arthroplasty were recruited. Three groups, of ten patients each, were formed: group A received moxifloxacin 400 mg orally 2 h (range 1.5-2.5) preoperatively, group B received moxifloxacin 400 mg orally 4 h (range 3.5-4.5) preoperatively and group C received moxifloxacin 400 mg orally 14 h preoperatively, followed by a second dose 2 h (range 1.5-2.5) preoperatively. During surgery, at the time of bone removal, a blood sample and aliquots of cortical and cancellous bone were collected and moxifloxacin concentrations were measured by HPLC. RESULTS: Mean plasma, cancellous bone and cortical bone concentrations were, respectively: 3.45, 1.89 and 1.43 mg/L for group A; 3.73, 1.81 and 1.56 mg/L for group B; and 6.26, 2.97 and 2.54 mg/L for group C. CONCLUSIONS: These data show a good penetration of moxifloxacin into both cancellous and cortical bone, with concentrations, after double dosing, exceeding the MIC90 for most pathogens involved in osteomyelitis and the clinic susceptibility breakpoint for Mycobacterium tuberculosis.

[Importation dengue]. / Dengue d'importazione.

We describe two cases of dengue fever (DF) serologicaly confirmed. In both, the clinical features are characterized by: fever, severe headache, myalgias and arthalgias, transient macule-papule rash, leukopenia and thrombocytopenia. The entire illness last few days and terminates abruptly without therapy. A history of travel to dengue-endemic areas and occurrence of other cases in a community are important reminders to include this disease in the differential diagnosis. The hemoagglutination inhibition test for DF at the Laboratory of Virology of the Istituto Superiore di Sanità on two collected sera, during the acute and convalescent phases, has showed a seroconversion. A problem is to advise patients to avoid endemic areas because the second exposure could induce DHF/dengue shock syndrome.

Penetration of rufloxacin into the cerebrospinal fluid in patients with inflamed and uninflamed meninges.

Forty-four patients scheduled for lumbar puncture (LP) were recruited to determine the level of penetration of orally administered rufloxacin into cerebrospinal fluid (CSF). The patients were divided into three clinical groups: those with normal CSF (groups A(1d) and A(7d)), those with aseptic meningitis (group B), and those with bacterial meningitis (group C). Members of group A(1d) received a single 400-mg rufloxacin dose, while group A(7d), B, and C constituents had a multiple-dose regimen (one 400-mg dose, followed by one 200-mg dose daily for 6 days). LP was performed on group A(1d) members 5 h after they had received treatment, while for group A(7d) it was undertaken 5 h after administration of the last dose. For group B, LP was performed 5 h after the first and the last doses, whereas for group C it was undertaken after the first, fourth, and last doses. Concentrations of rufloxacin in simultaneously collected CSF and plasma samples were determined. Mean CSF/plasma rufloxacin concentration ratios ranged from 0.57 to 0.84, depending on the study group. A higher, but not statistically significant, degree of penetration into CSF was observed in patients with bacterial meningitis than in those with normal CSF or aseptic meningitis. These data indicate that rufloxacin diffuses efficiently into the CSF of patients with either inflamed or uninflamed meninges.

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.

Norfloxacin prophylaxis for neutropenic patients undergoing bone marrow transplantation.

To prevent bacterial infections in the neutropenic post-transplant period, norfloxacin 400mg twice daily was administered as oral prophylaxis to 44 marrow recipients isolated in laminar airflow rooms (LAFRs). Patients had a mean age of 30 years (8-50) and a male/female ratio of 29/15. The mean duration of prophylaxis was of 41 days (20-80), that of neutropenia (PMN less than 1000 x 10(6)/l) of 31 days (6-76) and that of severe neutropenia (PMN less than 100 x 10(6)/l) of 19 days (10-55). All but two patients developed one or more febrile episodes (total episodes: 71), 33 of which were documented infections. Eighteen bacteraemias occurred and all were caused by Gram-positive cocci: five by coagulase-negative staphylococci (three methicillin resistant), four by coagulase-positive (one methicillin resistant), seven by streptococci (four S. sanguis, one S. milleri, one group B, one group C), and two by enterococci. All streptococcal and enterococcal strains, but only one MR coagulase-positive staphylococcus, proved to be resistant to norfloxacin. Norfloxacin was well tolerated and no prophylactic course had to be interrupted because of side effects. In conclusion, norfloxacin adequately prevents infections caused by Gram-negative bacilli in bone marrow recipients isolated in LAFRs, but Gram-positive infections still remain a problem in these patients indicating the need for improving this prophylactic regimen.

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.

[Study on the presence of Cryptosporidium in Umbria]. / Indagine sulla presenza del cryptosporidium in Umbria.

Cryptosporidium is an intestinal protozoan parasite belonging to the same family as Isospora and Toxoplasma. Cryptosporidium can cause severe, life-threatening enteritis in immunocompromised patients; he can also cause much less severe diarrhea in immunocompetent humans and in several animal species. Cryptosporidiosis has been diagnosed by identification of characteristic cocysts in fecal smear. In order to detect the small numbers of oocysts excreted, a modified Teleman-Miyagawa concentration technique was used. After, the faecal smears were stained by means of the dimethyl-sulfoxide (DMSO) acid-fast method. During 12 months, 157 specimens of faeces of patients with diarrhoea and 75 stool samples of asymptomatic humans were examined. Cryptosporidium was identified, only, in 2 of 157 stools of patients with diarrhoea. These two patients were less than 2 years of age. Cryptosporidial oocysts not were seen in the faeces of 75 asymptomatic humans and of 35 (only 20 with diarrhoea) immunocompromised patients. Failure to detect the agent in immunosuppressed patients in likely related to poor number of examinated cases. In conclusion, routine laboratory studies to identify Cryptosporidium in the stools of immunocompromised patients seem justified, since the parasite causes in these patients severe opportunistic also extra-intestinal infections.

[Bacteriostatic and bactericidal activity, resistance and tolerance of 16 strains of thermophilic Campylobacter to 12 antibiotic drugs]. / Attività batteriostatica e battericida, resistenza e tolleranza di 16 ceppi di Campylobacter termofilo verso 12 chemio-antibiotici.

The majority of gastrointestinal infections due to "thermophilic" Campylobacter is self limiting and does not need antibiotic treatment. Anyhow there are some serious cases (sepsis, persistent and relapsing gastroenteritis, severe immunodeficient patients) which require appropriate therapy. The susceptibility of 15 strains of Campylobacter jejuni and of 1 strain of C. coli, isolated from patients with acute gastroenteritis, has been studied against 12 antibiotics with the broth microdilution method at two different inocula (10(3)-10(4) CFU/ml and 10(7)-10(8) CFU/ml), and with the standard agar disk diffusion test, modified to allow sensitivity testing of Campylobacter. For each antibiotic, the geometric mean of MIC and of MBC and the concentrations of the various drugs needed for inhibition and killing of 50 and 90% of the strains (MIC-MBC50 and MIC-MBC90 respectively) have been calculated. Finally the percentage of resistant strains and the percentage of tolerant strains (ratio MBC/MIC: greater than or equal to 32) at low and high inoculum was determined. Erythromycin and aminoglycosides resulted the most active antibiotics against Campylobacter, being bactericidal as well as bacteriostatic at both low and high inoculum. Among the beta-lactams, cefotaxime was the most active, followed by piperacillin and ampicillin. Ceftazidime, aztreonam and rifampin were inactive. Ciprofloxacin, cotrimoxazole and tetracyclines showed some activity against Campylobacter at low inoculum. The agar disk diffusion method cannot be used for the "routinary" assay of susceptibility of Campylobacter, because it is a "naggy" microaerophilic organism.

Effect of protein concentration and blood clots on the "in vitro" anti-Pseudomonas aeruginosa activity of cefoperazone.

The effect of the protein content in the medium and blood clots on the anti-Pseudomonas aeruginosa activity of cefoperazone was studied and its activity against strains of the bacteria in the blood clots investigated. Medium protein content, blood clots and the localization of the microorganism all appeared to effect the antibacterial activity of cefoperazone: the therapeutic implications of these findings are briefly discussed.