The morphological response of urinary gram-negative bacteria (GNB) to ceftazidime (CAZ) was investigated in five patients with monomicrobial complicated urinary tract infections (UTI). The target bacteria were one strain of Pseudomonas cepacia (MIC: 0.39μg/ml), two strains of Pseudomonas aeruginosa (MIC: 1.56μg/ml for both) and two strains of Serratia marcescens (MIC: 50μg/ml for both). CAZ was efficiently excreted in the urine of four patients. The decrease of urinary CFU were progressive after the first injection, and the urinary viable bacteria were eliminated after the 2nd to 4th injection. Prominent filamentation was characteristically observed, regardless of the MIC, from the morphological responses of the urinary GNB by CAZ. The filamentous cells were markedly uneven in contour under light microscopy. Vacuole-like structures, dissociation of the cell wall from the cell membrane, and debris of bacteriolysis were observed under electron microscopy. We speculate that CAZ binds strongly to penicillin-binding proteins (PBPs), especially PBPs 3, of urinary GNB.

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Microbial contamination of three kinds of in-use jet type nebulizers with reservoir and disinfection methods for these nebulizers were investigated. Nine of 10 nebulizers tested were contaminated by 10³-10⁶ viable counts/ml of organisms. The primary contaminants were glucose nonfermentative gram-negative bacilli such as Pseudomonas cepacia and Flavobacterium meningosepticum. Therefore, it is clear that the jet mode nebulizer is easily contaminated by microbes. The nozzle portions (jets) of these types of equipment have been structurally difficult to disinfect with chemical disinfectants. In this study, chemical disinfectants were essentially ineffective. On the other hand, hot water was very effective within a short time period. Consequently, it is obvious that hot water (70°C, for 3 min) is the most useful disinfection method for jet mode nebulizers.

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The activity of 12 antibiotics and 5 disinfectants against 80 strains of methicillin-resistant Staphylococcus aureus (MRSA) isolated from 3 hospitals in 1988 (29 strains) and in 1991 (51 strains) was assessed. Vancomycin (VCM) and arbekacin (ABK) were the most effective of the test antibiotics, and benzalkonium chloride (BAC) and povidone-iodine (PVP-I) were effective as disinfectants gainst the MRSA tested. The coagulase type of the test MRSA strains was mainly type II. Strains coded 6736142 by the API Staph system, were all highly methicillin-resistant S.aureus (high MRSA) (≥100μg/ml). Based on the results of the range of MIC values, ABK, doxycycline (DOXY), minocycline (MINO), VCM and imipenem/cylastatin (IPM/CS) were effective against MRSA strains in 1988, while in 1991 ABK and VCM were effective. Among the above-mentioned antibiotics, in 1991 MRSA was more resistant to MINO, IPM/CS and OFLX than the MRSA in 1988 (p <0.01). Among the disinfectants tested, 0.1% BAC and 0.1% PVP-I were effective against MRSA strains. These results suggest that ABK and VCM are effective in the treatment of MRSA infections and that the use of 0.1% BAC or 0.1% PVP-I solution is suitable to control MRSA infection in these 3 hospitals.

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The clinical efficacy and safety of cefditoren pivoxil (CDTR-PI), a new oral cephem antibiotic, were evaluated in the treatment of skin and skin structure infections in a multicenter study. Forty-two patients with folliculitis, 1 with sycosis vulgaris, 10 with impetigo contagiosa, 12 with subcutaneous abscess, 3 with hidradenitis suppurativa, 30 with infected atheroma, 2 with chronic pyoderma, and 48 with secondary infection were evaluated for efficacy of this agent. CDTR-PI was given orally in a dose of 100 or 200 mg three times a day for 3-10 days. The overall efficacy rate was 80.4%(119/148). The bacteriological response rate was 86.1%(93/108). The incidence of side effects was 5.7%(9/159), and abnormal laboratory values were noted in 13 of 127 patients (10.2%). These results suggest that CDTR-PI is an effective, safe and useful drug in the treatment of skin and skin structure infections.

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Evaluation of the clinical efficacy and safety of Ro 06-2580 in the treatment of Pnessmocystis carinii pneumonia (PCP) was carried out in a total of 39 cases. The efficacy rate was 100% in 10 cases in which the definitive diagnosis was made, and 81.8% in 11 cases in which PCP was suspected clinically. Therefore, the total efficacy rate was 90.5%(19/21). In a total of 8 cases in which P. carinii shedding could be monitored, the organism was eradicated in all cases. Side effects, mostly G-I symptoms, were noted in 19.4%(7/36). Abnormal laboratory findings, such as elevated levels of GOT and/or GPT, were detected in 44.4%(16/36), although they were not marked. This study suggests that use of Ro 06-2580 for PCP is very effective, though side effects should be monitored closely.

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An investigation was conducted on respiratory infections caused by MRSA in a geriatric hospital to assess factors predisposing to respiratory infections and to find appropriate measure to control MRSA prevalence. In the present study, 57.2% of the causative organisms of nosocomial pneumonia were found to be Staphylococcus aureus, 94% of which were MRSA. Another 44% of the causative organisms were Pseudomonas aeruginosa (P. aeruginosa). Among cases of bacterial bronchitis occurring in the hospital, 51.7% were caused by S. aureus, 96% of which were MRSA, and 41.3% were caused by P. aeruginosa. The incidence of MRSA infections was higher than in the previous study performed 6 years ago. A rapid increase in the resistance of MRSA to various drugs has been reported. We have described a correlation between changes in the coagulase type of the isolated strains from type II to type VII and an increased use of minocycline in the hospital. Recovery of susceptibility of S. aureus strains to minocycline was observed after limiting minocycline use. Colonization of the upper respiratory tract by MRSA was supposed to be a predisposing factor to respiratory infections. The incidence of MRSA colonization in patients undergoing parenteral alimentation was 6 times higher in the nasal cavity and 10 times higher in the oropharynx than in patients undergoing oral alimentation. Moreover, the incidence of MRSA pulmonary infection was 10 times higher in the former patients than in the latter. Povidone iodine cream was applied to the nasal cavity of the colonized patients twice a day and povidone iodine solution spray to the oropharynx three times a day. In addition, cleaning the floor of the ward with 0.1% of benzalkonium chloride spray twice a day and ultraviolet light once a day together with environmental management by the staff resulted in an 86% reduction of the frequency of MRSA isolation from environment and a decrease in the incidence of MRSA infections in the hospital.

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Prophylactic chemotherapy is vitally important for emergency patients with serious diseases since infections are readily caused by contamination with indigenous bacteria, especially gram-positive cocci, in the emergency treatment of wounds and various kinds of diseases. We primarily administered cefazolin (CEZ), a first-generation cephem antibiotic, to 78 patients who were transferred to the intensive care unit at our emergency medical facility and who were exposed to contamination or infection with these bacteria, to evaluate the prophylactic effect of CEZ against infection with them. Infections did not occur in 55 (70.5%) of these patients after administration, but did occur in 28 (29.5%), by about the 10th day in hospital. Therefore, substituting other antibiotics for CEZ was required in these patiens. However, gram-positive cocci regarded as indigenous were not detected, even in the infected patients. The primary effect of CEZ against infection with indigenous bacteria was confirmed. Infections were observed in most of the patients with serious diseases and were considered to be due to decreased immunocompetence. Gram-positive cocci with multi-drug resistance, especially methicillin-resistant Staphylococcus aureus (MRSA), accounted for 72.2% of the causative organisms. The infections might have been predisposed to by the primary administration of CEZ. However, all of these organisms were resistant to the beta-lactam antibiotics, so these infections were nosocomial, developing after admission to hospital, and prevention of the onset was difficult. Thereafter these patients responded well to vancomycin, so the infections were not considered to be due to problems associated with primary administration of CEZ. Therefore, when the possibility of new drug resistance, the drug price, and the effects of the drugs on indigenous bacterial flora are considered, bearing in mind that these were nosocomial infections, the use of first-generation cephems is considered to be prefered for primary administration, even in emergency patients with serious diseases and decreased immunocompetence.

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