[A case of micafungin-hyposensitive Candida glabrata due to FKS2 gene mutation].

Candida glabrata was continuously isolated in cultured urine samples from a subject with thrombotic thrombocytopenic purpura. Yeast-like fungal phagocytosis found in gram staining led to agents being tested for antifungal susceptibility, revealing hyposensitivity to micafungin (MCFG) of MIC < 2 mg/mL. MCFG administered for 10 days failed to cure C. glabrata infection. To clarify why hyposensitivity occurred, we analyzed the FKS gene sequence using the PCR, finding a deficit of 3 bases coding phenylalanine at FKS2 gene amino acid 659. MCFG hyposensitivity may thus occur in long-term candin-class anti-fungal agent treatment. Candin-class agents have potent anti-fungal activity with fewer adverse effects and are widely used clinically. Hyposensitivity due to resistant C. glabrata species showed thus be considered in fungal infection treatment.

[A case of micafungin-hyposensitive Candida glabrata due to FKS2 gene mutation].

Candida glabrata was continuously isolated in cultured urine samples from a subject with thrombotic thrombocytopenic purpura. Yeast-like fungal phagocytosis found in gram staining led to agents being tested for antifungal susceptibility, revealing hyposensitivity to micafungin (MCFG) of MIC <2 mg/mL. MCFG administered for 10 days failed to cure C. glabrata infection. To clarify why hyposensitivity occurred, we analyzed the FKS gene sequence using the PCR, finding a deficit of 3 bases coding phenylalanine at FKS2 gene amino acid 659. MCFG hyposensitivity may thus occur in long-term candin-class anti-fungal agent treatment. Candin-class agents have potent anti-fungal activity with fewer adverse effects and are widely used clinically. Hyposensitivity due to resistant C. glabrata species showed thus be considered in fungal infection treatment.

[Macrolide resistance and detection in Mycoplasma pneumoniae at Kansai Medical University Hirakata Hospital].

Mycoplasma pneumoniae causes bronchitis and pneumonia predominantly in subjects 5 to 20 years old. M. pneumoniae is detected by measuring specific antibodies and/or isolating the microorganism, but the frequency of false-positive/negative results, and the culture time required until isolation pose problems. We detected M. pneumoniae using real-time PCR with clinical specimens. We also determined the drug sensitivity of isolated M. pneumoniae and searched for the gene mutation responsible for macrolide resistance. In 275 cases of suspected M. pneumoniae infection, positive cases in real-time PCR numbered 40 (14.5%). Of these, 16 showed positive culture (5.8%). Of these 16, A2063G point mutation that causes macrolide resistance was found in 12. Drug sensitivity testing showed resistance to clarithromycin (MIC> or =64 microg/ml) in 11 and susceptibility in 4 (MIC 0.0039 microg/ml). The clarithromycin resistance ratio was 75%. Growth was insufficient for testing in 1 case. M. pneumoniae was susceptible to minocycline and all quinolone drugs. M. pneumoniae detection using real-time PCR proved much more sensitive than conventional culture. Macrolide resistance results correlated well with genomic mutation. Our study's macrolide resistance ratio was high at 75% possibly due to a restricted subject population that had been administered macrolide drugs elsewhere but with an unsatisfactory outcome. The increasing number of reports on macrolide resistance requires that we monitor drug resistance trends, particularly among macrolide derivatives.

[Antibacterial activity of quinolones against various clinically isolated strains and evaluation of efficacy based on the pharmacokinetics/pharmacodynamics theory].

We compared the antimicrobial activities of oral quinolones, ciprofloxacin (CPFX), gatifloxacin (GFLX), garenoxacin (GRNX), levofloxacin (LVFX), moxifloxacin (MFLX), norfloxacin (NFLX), prulifloxacin (PUFX), and tosufloxacin (TFLX) using Streptococcus pneumoniae, Haemophilus influenzae, Streptococcus agalactiae, Streptococcus pyogenes, extended spectrum beta-lactamase(ESBL) producing Klebsiella pneumoniae, and methicillin-susceptible Staphylococcus aureus (MSSA) isolated from clinical materials. Based on the pharmacokinetics-pharmacodynamics theory, the target attainment rate at the area under the curve (AUC)/MIC of 120 or more for Gram-negative and 30 or more for Gram-positive bacteria was calculated using Monte Carlo simulation (MCS), and was assessed as the efficacy. GRNX showed the lowest MIC50 and MIC90 values (0.03 and 0.06 microg/ml, respectively) against S. pneumoniae, suggesting its potent antimicrobial activity. GRNX also exhibited the most potent antimicrobial activity against Gram-positive bacteria (S. agalactiae, S. pyogenes, MSSA) other than S. pneumoniae. The antimicrobial activity of CPFX against H. influenzae was most potent. The MIC50 and MIC90 values were 0.016 microg/ml each. However, the MIC50 and MIC90 values of the other agents were also favorable. PUFX showed the most potent antimicrobial activity against ESBL-producing K. pneumoniae. Both of MIC50 and MIC90 values were 0.06 and 1 microg/ml, respectively. On efficacy assessment using MCS, GRNX, GFLX, and MFLX showed a probability of 90% or more against S. pneumoniae and S. pyogenes. Against S. agalactiae, GRNX, MFLX, and GFLX showed a probability of approximately 60%. All agents showed a low probability against ESBL-producing K. pneumoniae; PUFX showed a maximum (43.63%). GRNX, MFLX, GFLX, and LVFX showed a probability of 90% or more against MSSA. Furthermore, we investigated the probability that the target value of resistance inhibition, an AUC/MIC of more than 200 against S. pneumoniae, is achieved. GRNX showed the highest probability (95.05%). It also exhibited a similar probability even when the target value was established as 250. Recently, the widespread use of quinolones has increased the number of quinolone-resistant bacteria. In the future, antimicrobial agents should be selected with respect to more potent therapeutic effects and resistance inhibition, and an appropriate dose and administration method must be employed.