Antimicrobial activity of superoxidized water.

We tested the antimicrobial activity of superoxidized water against methicillin-sensitive Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, Staphylococcus epidermidis, Serratia marcescens, Escherichia coli, Pseudomonas aeruginosa and Burkholderia cepacia. The number of bacteria was reduced below detection limit following incubation in superoxidized water for 10 s. The bactericidal activity of superoxidized water was similar to that of 80% ethanol, but superior to that of 0.1% chlorhexidine and 0.02% povidone iodine. We conclude that superoxidized water is a low cost but powerful disinfectant.

[Invasive pulmonary aspergillosis caused by aspiration of polluted water after nearly drowning].

A 21-year-old male nearly drowned in a reservoir by a traffic accident and he aspirated a large mount of polluted water containing Aspergillus fumigatus. On admission to our hospital, he was alert but cyanotic. Chest rentogenograms showed scatter infiltrative shadows in bilateral lung fields. We administered methylpredonizolon and antimicrobial agents immediately because of respiratory failure which was rapidly progressing. During the following six days, infiltrative shadows diminished but multiple nodular shadows in both lung fields appeared. The diagnosis of pulmonary aspergillosis was confirmed by serological and microbiological studies. Intravenous amphotericin B and oral itraconazol were administrated, and clinical improvement was observed.

[A study of virulence factors produced by MRSA strains isolated from blood samples].

Toxic shock syndrome toxin-1 (TSST-1) and enterotoxins are important virulence factors produced by Staphylococcus aureus. It is reported that these toxins are associated with septic shock and toxic shock syndrome. We investigated the toxin production and coagulase types of 701 MRSA strains isolated in Sasebo City General Hospital between 1994 and 1996 TSST-1 or/and enterotoxins were detected in 67% of all MRSA strains, and those were detected in 88% of MRSA strains isolated from blood samples. 45% of all MRSA strains produced both TSST-1 and enterotoxin C, and 70% of MRSA strains obtained from blood produced those toxins. Frequency of TSST-1 or/and enterotoxin production by MRSA strains isolated from blood samples was significantly higher than that by MRSA strains isolated from urine and pharynx (p < 0.05), and frequency of both TSST-1 and enterotoxin C production by MRSA isolates from blood was significantly higher than that by MRSA strains isolated from pharyngeal sample (p < 0.05). This study indicated that investigation of virulence factors produced by MRSA might give the useful information on prevention and treatment of MRSA infection.

[The clinical evaluation of MTD false-positive & false-negative results].

The usefulness of MTD (Amplified Mycobacterium Tuberculosis Direct Test) for a rapid diagnosis of tuberculosis was evaluated. A total of 400 clinical samples obtained from July, 1995 to June, 1997 were tested by MTD, direct microscopy and culture. The results of MTD and smear/culture were coincident in 387 out of 400 samples. Eight samples (2%) were MTD false-positive (i.e. they were MTD positive but smear and culture negative), and 5 (1.25%) were MTD false-negative (i.e. MTD negative but smear and/or culture positive). Despite a careful review of the clinical data of those patients whose samples showed discrepant results, the reasons of discrepancy were not clear in 2 (0.5%) of the 8 false positives and 3 (0.75%) of the 5 false negatives. In the other cases, the MTD false positives may be accounted for the presence of previous M. tuberculosis infection, the influence of anti-tuberculous medication and so on, and the MTD false negatives are most likely due to the presence of inhibitors (blood, for example) or to the small number of organisms in the specimens. It can be concluded that adequate samples should be obtained, and that MTD should be repeated in case of discrepant results.

Potential effects of erythromycin on host defense systems and virulence of Pseudomonas aeruginosa.

We evaluated several potential effects of erythromycin (EM) on host defense systems and the virulence of Pseudomonas aeruginosa. Peritoneal macrophages obtained from mice given 250 mg of EM per kg of body weight for 7 days by the intraperitoneal, intravenous, subcutaneous, or oral route produced significantly greater amounts of thymocyte-activating factors. These data suggest that EM enhances the in vivo production of cytokines, such as interleukins 1 and 6. Treatment of P. aeruginosa D4 with subinhibitory concentrations of EM enhanced the association of bacteria with murine Kupffer cells in vitro and increased bacterial clearance from the blood in mice. EM suppressed the in vitro production of exotoxin A, total protease, elastase, and phospholipase C by P. aeruginosa D4; exotoxin A production by P. aeruginosa PA-103; and total protease production by P. aeruginosa B16 and PAO1 in a generally dose-dependent manner. These data demonstrate that EM produces various effects in addition to its direct antimicrobial activity, suggesting that it has potential as an immunomodulator or bacterial virulence-suppressing agent against P. aeruginosa and other infections.

Comparative in vitro exoenzyme-suppressing activities of azithromycin and other macrolide antibiotics against Pseudomonas aeruginosa.

The inhibitory effects of azithromycin (AZM), a new 15-membered macrolide antibiotic, on the production of exotoxin A, total protease, elastase, and phospholipase C by Pseudomonas aeruginosa were determined, and the virulence-suppressing effects of AZM were compared with those of erythromycin (EM), roxithromycin (RXM), and rokitamycin (RKM). The effect of exposure of P. aeruginosa PA103 or B16 in cultures to sub-MICs of these macrolide antibiotics on the production of exoenzymes was determined. AZM suppressed the in vitro production of extracellular and intracellular exotoxin A by P. aeruginosa PA103 more than did EM, even at a concentration of only 2 micrograms/ml. At concentrations of between 4 and 32 micrograms/ml, AZM also inhibited total protease, elastase, and phospholipase C production by P. aeruginosa B16 more than did EM, RXM, and RKM. AZM was effective in suppressing exotoxin A and total protease production through 24 h of incubation in the presence of drug at sub-MICs, but it had no significant effect on either the growth of P. aeruginosa or its total protein production. Moreover, at a concentration of 4 micrograms/ml, AZM suppressed exoenzyme production by other strains of P. aeruginosa more than did EM. These findings indicate that AZM, EM, RXM, and RKM each has an inhibitory effect on exoenzyme production separate from the antimicrobial effect and that, of these macrolides, AZM has the strongest virulence-suppressing effect.

Trends in antimicrobial resistance of Streptococcus pneumoniae in Japan.

A total of 184 isolates of Streptococcus pneumoniae were recovered from the sputa of patients over a 5-year period in the Nagasaki area and were examined. A total of 30 strains were resistant to penicillin (MIC, > or = 0.10 micrograms/ml), 13 of which belonged to serotype 19B. These strains showed decreased susceptibility to other antimicrobial agents. Vancomycin, cefpirome, and imipenem were the most active agents tested.

In vitro and in vivo activities of sparfloxacin against Mycoplasma pneumoniae.

The in vitro and in vivo activities of sparfloxacin against Mycoplasma pneumoniae were compared with those of erythromycin, levofloxacin, ofloxacin, and minocycline. The MICs of sparfloxacin, erythromycin, levofloxacin, ofloxacin, and minocycline for 90% of the 43 M. pneumoniae strains tested were 0.063, 0.016, 0.5, 1, and 0.5 microgram/ml, respectively. In the experimental pulmonary M. pneumoniae infection model in Syrian golden hamsters, sparfloxacin was as effective as erythromycin when orally administered at 15 mg/kg twice daily for 5 days and more effective than erythromycin when orally administered at 10 mg/kg once daily for 5 days. Sparfloxacin was more effective than levofloxacin and ofloxacin in both dosing regimens. The peak concentrations of sparfloxacin in hamster sera after administration of single oral doses of 15 mg/kg were almost the same as those in human sera after administration of single oral doses of 200 mg (the usual clinical dose), and the half-life of sparfloxacin in hamster serum was shorter than that in human serum after administration of a single oral dose of 200 mg. These results suggest that sparfloxacin may be clinically useful for the treatment of M. pneumoniae infections.

In vitro and in vivo activities of macrolides against Mycoplasma pneumoniae.

We investigated the in vitro and in vivo activities of macrolides against Mycoplasma pneumoniae. In vitro MICs of azithromycin, erythromycin, clarithromycin, and roxithromycin were determined. Azithromycin was the most potent antimicrobial agent tested in vitro. Its MIC for 90% of the strains was 0.00024 micrograms/ml. MICs for 90% of the strains of erythromycin, clarithromycin, and roxithromycin were 0.0156, 0.0078, and 0.03125 micrograms/ml, respectively. In vivo activities were assessed in a pulmonary infection model with Syrian golden hamsters. We evaluated the in vivo effects on reduction of viable M. pneumoniae cell counts and on reduction of microscopic and macroscopic histopathologies for azithromycin, erythromycin, and clarithromycin given at 10 mg/kg once daily for 1 and 3 days and given at 15 mg/kg twice daily for 2.5 and 5 days. Azithromycin was significantly more effective than erythromycin or clarithromycin in the same regimens. Especially at 10 mg/kg once daily for 1 day, only azithromycin was significantly effective in the reduction of viable M. pneumoniae cells and histopathologies. These results show that azithromycin is more efficacious than the other drugs tested against M. pneumoniae pneumonia in hamsters. These data suggest that clinical studies of macrolides in human patients are warranted.

In-vitro and in-vivo activity of a new quinolone AM-1155 against Mycoplasma pneumoniae.

We investigated the in-vitro and in-vivo activity of a new quinolone AM-1155 against Mycoplasma pneumoniae, and compared it with ofloxacin, ciprofloxacin, lomefloxacin, tosufloxacin, erythromycin and minocycline. AM-1155 was the most potent agent in vitro of the quinolones tested. Its pre-treatment minimal inhibitory concentrations for 90% of the 41 strains (MIC90) was 0.06 mg/L. In contrast, pre-treatment MIC90 values for ofloxacin, ciprofloxacin, lomefloxacin, tosufloxacin, erythromycin, and minocycline were 1, 1, 2, 0.5, 0.0156, and 0.5 mg/L, respectively. Post-treatments MIC90s, which may reflect mycoplasmacidal potency, of AM-1155, ofloxacin, ciprofloxacin, lomefloxacin, tosufloxacin, erythromycin and minocycline were 0.125, 1, 2, 4, 0.5, 0.125 and 4 mg/L, respectively. In-vitro activities of antimicrobial agents were assessed in an experimental pulmonary infection model in Syrian golden hamsters. AM-1155 was the most effective agent among five antimicrobial agents (AM-1155, ofloxacin, tosufloxacin, erythromycin, minocycline) tested in terms of reduction in viable M. pneumoniae cells and in reducing macroscopic lung lesions. These results suggest that AM-1155 will be a useful antimicrobial agent for the treatment of M. pneumoniae infections.