We examined the prevalence of fluoroquinolone-resistant Neisseria gonorrhoeae isolates in Japan and the quinolone-resistance mechanisms in the organisms.
1. The prevalence of fluoroquinolone-resistant N. gonorrhoeae
The antimicrobial susceptibility of a total of 529 gonococcal isolates, including 27 from 1981 to 1984, 151 from 1993 to 1994, 154 from 1995 to 1996, and 197 from 1997 to 1998, to various agents were tested. The susceptibility of N. gonorrhoeae to fluoroquinolones has been decreasing dramatically during the observation period. The MICs₉₀ of norfloxacin, ciprofloxacin (CPFX), levofloxacin, and sparfloxain for the 197 gonococcal isolates from 1997 to 1998 were 64- to 256-fold higher than those for the 27 isolates between 1981 and 1984. The prevalence of fluoroquinolone-resistant N.gonorrhoeae isolates (MIC of CPFX≥1μjug/ml) increased remarkably. The prevalence rate (24.4%) of the fluoroquinolone-resistant N.gonorrhoeae isolates from 1997 to 1998 was significantly higher than that (0%) between 1981 and 1984 (p<0.001). However, there were no significant changes in the susceptibility of the isolates to various antimicrobial agents other than fluoroquinolones. We also evaluated the relationship between auxotype and fluoroquinolone resistance in N.gonorrhoeae. The MIC₉₀ of CPFX for the proline-requiring isolates was 8- to 512-fold higher than that for the other auxotype such as the argentine-requiring isolates or prototrophic type.
2. The quinolone resistance mechanisms in N.gonorrhoeae
Of 36 N.gonorrhoeae isolates moderately resistant to CPFX (MIC of 0.125 to 0.5μ/ml), 25 contained amino acid substitutions within the quinolone resistance-determining region (QRDR) of DNA gyrase subunit A (GyrA) alone and the remaining 11 contained amino acid substitutions in the QRDRs of GyrA and topoisomerase IV parC-encoded subunit (ParC). All 29 isolates resistant to CPFX (MIC≥ 1μg/ml) had a double amino acid substitution at position 91 and 95 in the QRDR of GyrA combined with a single or double substitution in the QDRD of ParC. The most frequently identified alteration was a serine (Ser.) to phenylalanine (Phe) at position 91 in GyrA and that was a serine to proline at position 88 in ParC. No single alteration in ParC, without the simultaneous presence of a resistance alteration in GyrA, was identified. These data suggest that alterations in GyrA play a central role in conferring fluoroquinolone resistance to N.gonorrhoeae, and that alterations in ParC play a complementary role in the development of fluoroquinolone resistance.
Male patients with gonococcal urethritis were treated with an oral dose of 200mg of pazufloxacin 3 times daily for 3 days. Of 42 gonococcal isolates only 28 (66.7%) were eradicated. The relationship between bacteriological response to pazufloxacin and alterations in GyrA and ParC was evaluated. All the wildtype isolates and the isolate containing a single amino acid substitution at position 75 or 95 were eradicated after pazufloxacin treatment. However, eradication rates in the isolates with a Ser-91 to Phe alteration in GyrA and multiple alterations in GyrA and ParC were 21.4% and 0%, respectively.

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Arbekacin (ABK) concentrations in serum and otolaryngological tissues were determined in patients who had undergone an operation. Maximum serum concentrations of ABK after intravenous infusion of 100mg and 200mg for 30 min were 8.1μg/ml and 14.9μg/ml, respectively, whereafter the serum concentrations decreased with the half-lives of 1.6h and 2.4h. The volumes of distribution were 11.1 L and 12.5 L respectively. ABK distribution into otolaryngological tissues was expressed as the tissue/serum concentration ratio. The ratios were 0.10-0.56 in otolaryngological tissues which were similar to the extracellular fluid space in the tissues. This implies that ABK is distributted into the extracellular fluid where MRSA organisms exist. From pharmacokinetic consideration, the ABK concentrations in the extracellular fluid of the tissues examined will be maintained at a high enough level more than MICK, as well as the serum concentration in both cases of 100mg and 200mg administration.

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Recently there was an outbreak of methicillin-resistant Staphylococcus aureus (MRSA) in an Oemergency ward in our hospital. MRSA is currently widespread throughout the hospital, including emergency ward, and some patients have died from MRSA infections. More persons have been infected orcolonized despite enforcement of strict infection control measures. Since July 1997, we have applied blanket use of mupirocin nasal ointment only in the emergency ward. Intranasal mupirocin is applied three times a day for three days to all patients already in the ward. New patients are given empirical intranasal mupirocin(same regimen)after admission, for nine months. We prospectively investigated the number of infected and colonized patients in the emergency ward and open wards, including the pulmonary disease unit, before and after blanket use of mupirocin. The prevalence of MRSA infection and carrier state had decreased markedly in both the emergency ward and open wards. Blanket use of intranasal mupirocin in the emergency ward is effective not only in the emergency ward itself but in other wards as well.

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