Acute Q fever is the generic name fbr febrile diseases such as pneumonia and bronchitis mainly occurring after transtracheal infection of Coxiella burnetii, an obligate intracellular parasite of Coxiella belonging to the Rickettsia family, in a broad sense, and difficult to differentiate from other respiratory infections by clinical features alone. In addition to respiratory ailments, diseases including hepatitis and fever of unknown origin are also observed. In many cases, acute Q fever is transient and febrile, showing influenza-like symptoms such as fever, malaise, and arthralgia mainly in summer, and is self-limiting with a good prognosis. Because it may lead to chronic Q fever and a poor prognosis in the form of endocarditis, it is desirable to progressively treat patients upon strong suspicion or definite diagnosis of the disease. Definite diagnosis is currently based on a significant increase in serum antibody titer, but many cases take a long time to achieve a sufficient increase in antibody titer, so it must be determined several times. The results of PCR using respiratory tract specimens in the acute phase are also very useful for diagnosis, but development of a rapid, highly sensitive, simple diagnostic method is much desired. In treatment, β-lactam antibiotics with low cell penetration are ineffective and tetracyclines is the drug of first-choice. Macrolides, new-quinolones, and rifampicin are also effective, but treatment must be continued one or two weeks after fever subsides in a few days after treatment is started.

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Although the MIC of antifungal agents is usually used as the recommended treatment dosage, determining the MIC using the turbidity method requires stirring and is non-quantitative. The newly developed imaging method for measuring MIC, which utilizes a CCD camera, does not have these drawbacks. We investigated the usefulness of the imaging method for measuring MICs for define and clinically obtained fungal strains by comparing our results obtained using the imaging method with those obtained using the standard turbidity method recommended by define and the Japanese Society for Medical Mycology. Using Candida albicans (ATCC 90028), Candida albicans (ATCC 90029), Candida glabrata (ATCC 90030), Candida parapsilosis (ATCC 90018), Candida krusei (ATCC 6258) and 60 other Candida strains (C. albicans: 22; C. glabrata: 10; C. parapsilosis: 19; C. tropicalis: 9) isolated from blood, the MIC of various was measured using “Yeast FP”(Eiken Kagaku). With this method, antifungal agents the attenuation of transmitted light produced by yeast aggregation was recorded using a CCD camera attached to a microscope. The intensity of the transmitted light was then determined using image processing to obtain the growth area; the growth endpoint was then determined from the growth area, and the MIC was calculated. The MICs were consistent with the values published by NCCLS M 27-T in six out of nine samples measured using the imaging and turbidity methods. However, the results of the turbidity method were more consistent with the values published by the Japanese Society for Medical Mycology than the results of the imaging method (14 out of 20 samples for the turbidity method vs. 17 out of 20 samples for the imaging method). The differences between the imaging-measured MICs and the turbidity-measured MICs were within one standard deviation of each other for all clinically isolated strains expect for C. albicans and C. parapsilosis; thus, the two measurement methods were highly correlated. MIC measurements in clinical isolates using the imaging method were not significantly different from those obtained using the conventional method. In view of the simplicity of its procedure, the imaging method may be very useful for calculating the MIC of antifungal agents in clinical isolates.

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Rats with subcutaneous infected pouches were treated with cefazolin (CEZ; 10mg/kg or 20mg/kg) using an intravenous bolus injection (IV) or drip infusion (DIV) for 1 or 2 hours. Samples of serum and infection exudate in the pouch were obtained at regular intervals after the administration of CEZ. Bacterial counts in the infection exudate were assessed using quantitative cultures. The concentration of CEZ in serum and infection exudate was measured using a bioassay. When rats were treated with the same dose, the effects of CEZ in the IV group were significantly stronger than those in the DIV groups. Moreover, the effects of CEZ in the 10 mg/kg IV group were significantly stronger than those in the 20mg/kg DIV groups, even though the dosage was half. The maximum concentrations (C_max) of CEZ in the serum of the IV group were 1.3-3.8 times higher than those of DIV groups. However, the half-life (T_1/2) of CEZ in the serum of the DIV groups was longer than that in the IV groups by 0.6-2.1 hours. In the serum, the drug level was maintained at a level over the minimum inhibitory concentration (time above MIC) longer in the DIV groups than in the IV group (at a dosage of 10 mg/kg: IV, 2.8 hours; 1 h DIV, 3.7 hours; 2 h DIV, 4.4 hours; at a dosage of 20 mg/kg: IV, 2.9 hours; 1 h DIV, 5.9 hours; 2 h DIV, 4.6 hours). The C_max values for CEZ in the infection exudate were 1/10-1/20 as high as those in the serum. The T_1/2 values for CEZ in the exudate were longer than those in the serum by 0.8-2.0 hours. The time above MIC values for CEZ in the infection exudate were much shorter than those in the serum. Contrary to the results in the serum, the time above the MIC of CEZ in the exudate of the IV group was longer than those in the DIV groups (at a dosage of 10 mg/kg: IV, 1.4 hours; 1 h DIV, 0.1 hours; 2 h DIV, 0 hour; at a dosage of 20 mg/kg: IV, 2.7 hours; 1 h DIV, 1.8 hour; 2 h DIV, 0 hour). The high serum level of CEZ achieved by the bolus IV should accelerate tissue penetration of the drug, producing stronger antibacterial effects. Thus drugs with protein binding rates as high as that of CEZ should probably be administered by bolus IV.

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The in vitro antifungal activity of micafungin (MCFG) against Candida and Aspergillus species, clinically isolated in Japan between October 2001 and August 2002, were compared with those of amphotericin-B, miconazole, fluconazole, itraconazole and 5-fluorocytosine using the broth microdilutionmethod, as specified by the National Committee for Clinical Laboratory Standards (NCCLS) documents M 27-A and M 38-P. The MIC₉₀ levels of MCFG for Candida albicans (including fluconazole-resistant isolates), Candida tropicalis, Candida glabrata, and other Candida spp. were 0.0625μg/mL or lower, which were lower than those for the other antifungal agents tested. The MICs of MCFG for Candida parapsilosis and Candida guilliermondii ranged from 0.025 to 1μg/mL, which were comparable to or slightly higher than those for the other antifungal agents tested. The MICs of MCFG for Aspergillus fumigatus, Aspergillus niger, Aspergillus terreus, Aspergillus flavus and other Aspergillus sp. ranged from 0.002 to 0.0313μg/mL, which were lower than those for the other antifungal agents tested. None of the isolates showed a lowered susceptibility to MCFG, as indicated by the fact that the MIC values of MCFG were distributed within 2 dilutions for each Candida species and below 0.0313μg/mL for all Aspergillus isolates.

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We analyzed the clinical efficacy and plasma trough concentration of teicoplanin (TEIC) in methicillin-resistant Staphylococcus aureus (MRSA) infections in emergency and critical care medicine to find the adequate dosage of this anti-MRSA agent. Results are as follows:
1. The clinical efficacy of TEIC against 14 cases of pneumonia, 1 of septicemia, and 1 of pleuritis due to MRSA was 62.5%.
2. The bacteriological effectiveness of TEIC consisted of 3 eradicated, 2 decreased, 5 replaced, and 6unchanged. The monomicrobial infection group contained more eradicated and decreased cases than the polymicrobial infection group. In the polymicrobial infection group, slightly more cases were replaced by Pseudomonas aeruginosa simultaneously isolated with MRSA than in the monomicrobial infection group.
3. No case administered TEIC was found to have any side effects or abnormal laboratory findings.
4. The TEIC plasma trough concentration reached plateaued its steady state by treatment day 6. Patients also showed over 10μg/mL of TEIC plasma trough concentration as the mean on day 6. Effective cases showed a higher mean TEIC plasma trough than ineffective cases. Cases with a TEIC plasma trough over 10μg/mL on day 8, experienced greater effectiveness than those with a trough of less than 10μg/mL.
5. These results indicate that TEIC is effective against MRSA infections, but that a higher TEIC plasma trough concentration is necessary for treating severe cases in emergency and critical care medicine. How to use TEIC to treat MRSA infections more effectively usage is an issue requiring further study.

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