Sadao Tamada

Procalcitonin and severity of community-acquired pneumonia

The purpose of this study was to clarify the relationship between procalcitonin and the severity and prognosis of community-acquired pneumonia. The subjects were 162 patients with community-acquired pneumonia (disease severity, mild, 39 patients; moderate, 81 patients; severe, 37 patients; and super severe, 5 patients) in whom we examined the serum procalcitonin concentration at the start of treatment; we determined the relationship of procalcitonin status with disease severity and prognosis. The results showed that procalcitonin was positive in 12.8% of the patients with mild disease, 27.1% of the patients with moderate disease, 59.5% of the patients with severe disease, and 80.0% of the patients with super severe disease. The mortality of procalcitonin-positive patients was 37.7%, whereas that of the procalcitonin-negative patients was 12.8%. Based on the above findings, it is concluded that the more severe the community-acquired pneumonia, the higher is the positivity rate for procalcitonin, and the prognosis in procalcitonin-positive patients is worse than that in procalcitonin-negative patients.

Clinical features of Proteus mirabilis pneumonia

In this study, we clinically reviewed 13 patients with Proteus mirabilis pneumonia who were admitted for treatment to Kawasaki Medical School Kawasaki Hospital, Okayama, Japan, between April 2006 and July 2009. Clinical features were retrospectively reviewed. Results showed that: (1) hospital-acquired pneumonia occurred in elderly patients with underlying diseases such as cerebrovascular disease; (2) some patients had complications of urinary tract infection due to P. mirabilis; (3) preadministration of antibacterial agents did not become a risk factor; (4) resistance for levofloxacin (LVFX) was observed; (5) prognosis was comparatively good (effective rate 84.7%).

Clinical features of Escherichia coli pneumonia

Escherichia coli pneumonia was clinically reviewed. Twenty-two patients with E. coli pneumonia were admitted for treatment to Kawasaki Medical School Kawasaki Hospital, between January 2006 and December 2008. Clinical features were retrospectively reviewed. Results showed that: (1) hospital-acquired pneumonia occurred in elderly patients with underlying diseases, such as cerebrovascular disease, diabetes mellitus, or chronic obstructive pulmonary disease; (2) more patients had complications of urinary-tract infection or alimentary infection due to E. coli; (3) previous administration of antibacterial agents did not become a risk factor; (4) resistance to ampicillin (ABPC) and levofloxacin (LVFX) was observed; and (5) mortality was 22.7%.

Sparfloxacin, a New Generation Fluoroquinolone against S. pneumoniae Respiratory Infections

Streptococcus pneumoniae is an important pathogen in acute respiratory tract infection. Until now, there have been no fluoroquinolones with sufficient activity against S. pneumoniae infections. Sparfloxacin, a newly developed fluoroquinolone, has potent antimicrobial activity against various kind of respiratory pathogens, including S. pneumoniae.[l,2] We investigated the in vitro activity [minimum inhibitory concentration (MIC)] of sparfloxacin against clinically isolated strains of S. pneumoniae and compared it with the in vitro activities of other fluoroquinolones. The activity of sparfloxacin was also studied in experimental S. pneumoniae infections in mice. In addition, the clinical efficacy of sparfloxacin against S. pneumoniae infection was evaluated in a nationwide multicentre collaborative clinical trial involving 117 patients. The activity of sparfloxacin against S. pneumoniae was superior to that of other new fluoroquinolones at an MIC distribution of 0.0125 to 100 mglL (table I). Male ICR mice were infected with approximately lOs colony-forming units (CFU) of S. pneumoniae (J4 strain) and treated with sparfloxacin, ofloxacin, and bacampicillin. Treatment was initiated 12 hours postinfection. At 12-hourly intervals for 5 days, mice received the following oral dosage regimens: sparfloxacin 5, 10 or 20 mg/kg; ofloxacin 5, 10 or 20 mg/kg; or bacampicillin I or 5 mg/kg. The survival rate of mice treated with sparfloxacin was higher than that with ofloxacin at any of the dosages. The survival rate of mice treated with sparfloxacin 20mg twice daily (75%) was similar to that of mice treated with bacampicillin 5mg twice daily (62.5%). Mice treated once daily with sparfloxacin 20mg showed higher survival rates than those treated with sparfloxacin lOmg twice daily (fig. 1). In the clinical study of sparfloxacin for the treatment of various S. pneumoniae infections, a high efficacy rate of 89.1 % was obtained with sparfloxacin 100 to 300mg daily for 14 days. The

Effects of Fluoroquinolones on Experimental Pneumonia Caused by Penicillin-Resistant Streptococcus pneumoniae in Mice

The in vitro and in vivo activities of several fluoroquinolones, ampicillin and cefteram-pivoxil were investigated against penicillin-resistantStreptococcus pneumoniae (PRSP). The MIC90s of sparfloxacin, levofloxacin, tosufloxacin, AM-1155, ampicillin, and cefteram-pivoxil for 13 PRSP strains were 0.78, 3.13, 0.39, 1.56, 3.13, and 3.13 μg/mL, respectively. An experimental fatal pneumonia was induced by intranasal inoculation of PRSP No. 65 in CBA/J mice. The fluoroquinolones were effective against the experimental pneumonia, but ampicillin and cefteram-pivoxil were not sufficiently effective. The oral 50% effective doses (ED50) of sparfloxacin, levofloxacin, tosufloxacin, and AM-1155 on the experimental pneumonia were 6.09, 49.3, 5.07, and 8.59 mg/kg/dose, respectively, when treatment was initiated 3 hours after infection and were 30.0, >50, 17.7, and 45.9 mg/kg/dose, respectively, when treatment was initiated 24 hours after infection. These results suggest that some fluoroquinolones such as sparfloxacin, tosufloxacin and AM-1155 may be effective in the treatment of pneumonia due to PRSP in humans.

Nonimmunocompromised Mouse Model of Penicillin-Resistant Streptococcus pneumoniae Pneumonia

Penicillin-resistant strains ofStreptococcus pneumoniae (PRSP) are a growing problem, both in Japan and elsewhere. To study therapeutic approaches to respiratory infection by these resistant bacteria, we identified two clinically isolated PRSP strains which exhibit strong virulence against nonimmunocompromised CBA/J mice. Most mice infected with these strains die of pneumonia within two weeks. In infections by one strain, survival rates were slightly improved by bacampicillin doses of 20 mg/kg/day for five days but not by lower doses. Survival rates following infection by the other strain were unaffected by bacampicillin at any dose tested. We believe that our animal model of PRSP pneumonia using these two strains can be useful for evaluating therapy of PRSP infections.