Tadashi Shiraishi

Evaluation of the Bactericidal Activity of Povidone-Iodine and Commercially Available Gargle Preparations

Objective: Encouragement of gargling is important for the control of opportunistic and community-acquired infections. In hospitals, a povidone-iodine (PVP-I) gargle is used frequently. However, at pharmacies in the community a variety of gargles containing various ingredients are now available. In view of this, we conducted a study to compare the bactericidal activities of a PVP-I gargle with those of other commercially available gargles. In addition, we asked about the feeling after use by questionnaire. At middle schools in our city, we investigated whether the encouragement to use the PVP-I gargle had an effect on the absence rate from school due to common cold and influenza. Methods: In vitro, using 3 strains of gram-positive and 4 strains of gram-negative bacteria as the test strains, the bactericidal activities of the PVP-I, chlorhexidine gluconate (CHG) and cetylpiridium chloride gargles (CPC) were compared by the contact test method. In vivo, with subjects in groups of 6 each, the reduction rate in the oral bacterial count after gargling as compared to the baseline count before gargling was determined and compared among the 3 gargling agents used. In addition, a questionnaire study was conducted to compare the feeling after use of the 3 gargling agents. Whether the absence rate due to common cold and influenza changed by encouraging the use of the PVP-I gargle was determined by comparing a middle school where the PVP-I gargle was used and other middle schools where it was not. Results: (1) PVP-I killed all the test strains after 30 s of exposure. (2) The mean reduction rate in bacterial count immediately after gargling was 99.4% for PVP-I, 59.7% for CHG and 97.0% for CPC. (3) Findings of the questionnaire study revealed that the PVP-I gargle was evaluated highest in terms of taste, feeling after gargling and odor among all the gargles tested. (4) At the middle school where the use of the PVP-I gargle was encouraged, the absence rate due to common cold and influenza was significantly lower as compared to those at middle schools where another gargle was used. Conclusion: Of the 3 gargles tested, PVP-I showed the highest bactericidal rate and the highest reduction rate in oral bacterial count. Encouragement of the use of the PVP-I gargle contributed to the decrease in absence rates due to common cold and influenza, indicating that encouragement of gargling with PVP-I is useful for the prevention of common cold and influenza.

Pharmaceutical and Bacteriological Study on Povidone-Iodine Sugar Ointment

Povidone-iodine sugar ointment is an excellent preparation for the treatment of decubitus. It has been used as an intrahospital preparation made according to the formula each hospital decided on from experience. Although commercial products have also been developed and used, they are too expensive. The efficacy of a povidone-iodine sugar ointment formulation which can be prepared by a single method and which has the stability and antibacterial activity equal to commercially available products was evaluated. As the test drugs, one commercially available product (UP), and three preparations with different formulas (P-1, P-2 and P-3) were used. All of these test drugs were stored at 20 and 40 degrees C. Specimens were sampled immediately after storage and after 20, 60, 90, 120 and 150 days and examined pharmaceutically (measurement of pH value and determinations of available iodine and sucrose levels). For the determination of bacteriological effects, 5 standard strains of 5 genera and 5 strains of methicillin-resistant Staphylococcus aureus (MRSA) were used and the time required to kill the bacteria was determined. For UP and P-3, no changes were seen pharmaceutically after 150 days of storage at 20 and 40 degrees C. However, MRSA could not be killed within 30 min. P-1 and P-2 showed remarkable changes pharmaceutically after 60 days of storage at 40 degrees C and could not be used any more. It became possible to make a preparation of povidone-iodine sugar ointment which has a stability almost similar to that of UP. Moreover, such a preparation can be made at low cost. However, since the bactericidal activity against MRSA was not higher than those of other drugs, the future task is to improve the bactericidal activity.

A survey of the appropriate use of antiseptic agents in the operating room of several key health care facilities. A comparison between surveys in 2000 and 2004.

Since 2000, new hand and environmental hygiene guidelines have been published by the Center for Disease Control and Prevention (CDC) based on scientific evidence. Accordingly, we expected that the use of disinfectants in clinical settings had been changed. To compare the use and amount of disinfectants before and after the publication of these guidelines, we conducted a questionnaire-based survey on the use of antiseptic agents in operating rooms (ORs) in 6 key hospitals over a period of a month in 2000 and 2004. As a result, the amount of disinfectants used in ORs was reduced in all hospitals in 2004. Especially, amphoteric detergents and glutaral products showed significant reductions in the total amount used in the 6 hospitals, by 94.8 and 96.8%, respectively. The use of povidone-iodine (PVP-I) was decreased by 23.4% overall, although it was increased in 3 hospitals by 11.0–58.6%. The number of applications of PVP-I on the surgical site did not change; however, the site was left to dry without wiping after PVP-I application more frequently in 2004 than in 2000. The time for surgical scrubbing was shortened in 2004, but brush scrubbing was still used as often as in 2000. Many of the hospitals used brush scrubbing in conjunction with alcohol-based rubs. These results indicated changes in infection control measures in hospital settings after publication of the new CDC guidelines; environmental disinfection had been limited and excessive use of disinfectants reevaluated.

Errata: Economic Evaluation of mFOLFOX6-based First-line Regimens for Unresectable Advanced or Recurrent Colorectal Cancer Using Clinical Decision Analysis

 We evaluated four representative chemotherapy regimens for unresectable advanced or recurrent KRAS-wild type colorectal cancer: mFOLFOX6, mFOLFOX6+bevacizumab (Bmab), cetuximab (Cmab), or panitumumab (Pmab). We employed a decision analysis method in combination with clinical and economic evidence. The health outcomes of the regimens were analyzed on the basis of overall and progression-free survival. The data were drawn from the literature on randomized controlled clinical trials of the above-mentioned drugs. The total costs of the regimens were calculated on the basis of direct costs obtained from the medical records of patients diagnosed with unresectable advanced or recurrent colorectal cancer at Yamagata University Hospital and Yamagata Prefecture Central Hospital. Cost effectiveness was analyzed using a Markov chain Monte Carlo (MCMC) method. The study was designed from the viewpoint of public medical care. The MCMC analysis revealed that expected life months and expected cost were 20 months/3,527,119 yen for mFOLFOX6, 27 months/8,270,625 yen for mFOLFOX6+Bmab, 29 months/13,174,6297 yen for mFOLFOX6+Cmab, and 6 months/12,613,445 yen for mFOLFOX6+Pmab. Incremental costs per effectiveness ratios per life month against mFOLFOX6 were 637,592 yen for mFOLFOX6+Bmab, 1,075,162 yen for mFOLFOX6+Cmab, and 587,455 yen for mFOLFOX6+Pmab. Compared to the conventional mFOLFOX6 regimen, molecular-targeted drug regimens provide better health outcomes, but the cost increases accordingly. mFOLFOX 6+Pmab is the most cost-effective regimen among those surveyed in this study.

Effects of Serum Sodium Concentrations on Nausea and Vomiting after Moderately Emetogenic Chemotherapy

 Chemotherapy-induced nausea and vomiting (CINV) is the most unbearable adverse effect of chemotherapy. The antiemesis guidelines of the National Comprehensive Cancer Network indicate that hyponatremia is a risk factor for CINV, although the relationship between the incidence of CINV and hyponatremia has not been sufficiently studied. This two-center prospective observational study evaluated whether low serum sodium concentrations were a risk factor for CINV. The study included 34 patients who were scheduled to receive first-line carboplatin- or oxaliplatin-based chemotherapy for gynecological or colorectal cancers. Patient diaries were used to record the daily incidences of CINV events during a 5-day period. The patients were divided based on the median serum sodium concentration into a low Na+ group (<141 mEq/L) and a high Na+ group (≥141 mEq/L). The incidences of delayed nausea were 27.8% in the high Na+ group and 62.5% in the low Na+ group (p=0.042), with complete control rates (no vomiting, rescue medication, or grade 2 nausea) of 77.8% and 43.8%, respectively (p=0.042). The time to complete control failure in each group was analyzed using the Kaplan-Meier method, which revealed a significantly shorter time in the low Na+ group (p=0.03). Therefore, these results indicate that low serum sodium concentrations may increase the risk of CINV.

A Comparison of the Stability and the Antibacterial Activities of Povidone-Iodine Sugar Ointments which were Prepared in Our Hospital and Manufactured in a Company.

This study was designed to estimate the difference in the stability and the antibacterial activity between PVP-ISU and U-pasta®, (UP) of Povidone-iodine sugar ointments which were prepared in our hospital and manufactured in a company. Observed were the changes in these two preparations which were preserved throughout the experimental period of 7, 30 and 60 days and at the temperatures of 20 and 40°C. The stability of each sample was investigated on pH value, available iodine, and sugar quantity. The bacteria tested were six strains of two strains each of MRSA, P. aeruginosa and P. mirabilis isolated from the decubitus of patients.In PVP-ISU maintained for 30 days at 40°C, the findings revealed that pH value dropped from 4.0 to 2.9 and the concentrations of available iodine and sugar decreased to 74.7% and 41.1% respectively. When storing up to 60 days at 40°C, the pH value lowered to 2.7, the dissolution of sugar was remarkably witnessed, and the concentration of available iodine was recognized as being only 11%. However, all of the strains tested were killed within 10 min. On the other hand, in UP sustained for 60 days at 40°C, no remarkable changes were observed except for a slight change in the pH value (4.7→4.0).These results suggest that PVP-ISU, in which the stabilizing agents are not contained, cannot be used for an extended time because it cannot maintain the proper stability of pH, sugar and available iodine at a high temperature (40°C). However, UP may possibly be used safely longer than 60 days even if it were stored at a high temperature (40°C).

Susceptibility of clinical isolates to habitual disinfectants.

Susceptibility of 353 bacterial strains, composed of 6 genera and 9 species, which were isolated recently from various clinical materials in Yamagata University Hospital, to 4 disinfectants, chlorhexidine gluconate (CHG), benzalkonium chloride (BAC), saponated cresol (SAC), and povidone iodine (PVP-I), was examined.1.All of the clinical isolates tested were sensitive to SAC and PVP-I, however, susceptibility of the isolates to CHG and BAC varied from species to species and also from strain to strain. 2.Most of the strains Serratia marcescens, Pseudomonas cepacia, Proteus mirabilis and Pr. vulgaris seemed to be insensitive to CHG, though they were sensitive to BAC.3.Many strains of Ps. cepacia were resistant to not only CHG, but also BAC. 4. Most of the strains of Staphylococcus aureus, Sta.epidermidis, Escherichia coli, Klebsiella pneumoniae, and Ps. aeruginosa were estimated to be sensitive to CHG and BAC.These results indicate that the resistant strains against CHG and BAC at the concentration recommended for disinfection of are be existent in some species of gram-negative bacteria of clinical isolates.