After HIV protease inhibitors became available in 1995, highly active antiretroviral therapy (HAART) has become a key element of in the treatment of HIV, and HIV-related deaths have decreased dramatically. Nevertheless, current therapies cannot eradicate HIV completely and drugs must be taken continuously for a long time. Today, we are confronted by severe adverse effects of long-term antiretroviral therapy and by viral resistance because of poor patient compliance with HAART, making it necessary to very carefully consider when and which drugs to use. The number of CD 4₊ lymphocytes, viral load, and clinical manifestations need to be taken into account when deciding to initiate antiretroviral therapy. Once the patient is on therapy, laboratory tests, including viral load, CD 4₊ count and the patient's clinical condition must be monitored to evaluate the effectiveness of therapy. Potent, tolerable, and convenient drugs are needed to improve compliance. New drugs are now being developed by several companies and are expected to become available for clinical use.

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Ketolide antibacterial agents have been under development worldwide as a new class of antibacterial agents. Initial research and development of ketolide antibacterials has been aimed at identifying characteristic properties of ketolide compounds, and telithromycin, the agent that has been developed the furthest has been used clinically in many countries. The chemical structure of ketolides is characterized by a ketone group at position-8, and bacteriologicaly they exhibit potent antibacterial activity against pathogenic bacteria of respiratory and otorhinological infections, such as gram-positive cocci, Haemophilus, atypical microorganisms, and intracellularly parasitic bacteria. Telithromycins characterized by potent activity against penicillin-, macrolide-and quinolone-resistant Streptococcus pneumoniae, and there is no cross-resistance with other antibacterial agents.

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We designed a set of primers on the 16 S rRNA gene to directly detect Mycoplasma pneumoniae by PCR in clinical specimens from patients with respiratory infections. The sensitivity of the primers was 2 CFU/tube under the following conditions: 35 cycles of 15 sec at 94°C, 15 sec at 53°C and 15 sec at 72°C /cycle. We therefore judged the PCR results to be positive if the CFU for M. pneumoniae in a clinical specimen was 1.1×10³. The results of the PCR were obtained in about 2.5 h. We then used the PCR to examine 783 clinical specimens (epipharynx [n=612], throat [n=141], ear discharge [n=12] etc.) collected from pediatric patients between May 2002 and January 2003. The PCR results were positive in 79 cases (10.1%); 58/291 cases (19.9%) corresponded to specimens from patients with pneumonia, 13/207 cases (6.3%) to specimens from patients with acute bronchitis, 2/130 cases (1.5%) to those from patients with acute pharyngitis and 2/45 cases (4.4%) to those from patients with acute upper respiratory infections. The percentage of PCRpositive cases was significantly higher among the patients with lower part respiratory tract infections (x²=53.3008, p=0.0000). Among the patients with pneumonia, 65 were diagnosed with M. pneumoniae based on a significant rise or high antibody titer for M. pneumoniae as determined by the PA or CF test, and 46 of these cases were PCR-positive (70.8%). We also investigated the correlation between the antibiotics used before PCR and the PCR results in these 65 cases. Of the total of 43 cases, 21 not treated with antibiotics before PCR and 22 cases given oral β-lactam agents ineffective against M. pneumoniae, 38 (88.4%) were PCR-positive, whereas only 3 (23.1%) of the specimens from 13 patients treated with macrolides or new quinolones effective against M. pneumoniae were PCR-positive. We concluded from these results, that the PCR is very useful in selecting suitable chemotherapeutic agents for patients not treated with antibiotics, however it may be necessary to consider the influence of days after to develop infection on PCR results.

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We studied the development of resistance to pazufloxacin (PZFX) and ciprofolxacin (CPFX) in Staphylococcus aureus using a model simulating the serum level after drip infusion of PZFX mesilate and CPFX hydrochloride in humans, obtaining the following results:
1) In the model simulating the serum level after drip infusion of PZFX mesilate (500mg) or CPFX hydrochloride (300mg), PZFX mesilate showed greater bactericidal activity, reflected AUC/MIC and C_max/MIC.
2) From the population analysis using culture broth after the CPFX simulation model, CPFX-resistant subpopulations were detected at concentrations of 1-4μg/mL and 10-40μg/mL. No obvious PZFX-resistant subpopulations were detected in the PZFX simulation model.
3) MICs of CPFX against isolates from culture broth after the CPFX simulation model increased 4-to 32-fold and additional amino acid changes were seen in DNA gyrase in isolates with MICs increased over 4-fold. No differences were in seen MICs between isolates from culture broth after the PZFX simulation model and the parent strain and no additional amino acid changes were seen in either DNA gyrase or topoisomerase IV.

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