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International Journal of Infection Control
Contact: Dr. Michael A. Borg IFIC Chair
ijic@theific.org
(March 28, 2008)

An Innovative Method for the Control of Legionella Infections in the Hospital Hot Water Systems with a Stabilized Hydrogen Peroxide-Silver Formulation Hillel Shuval1,2, Rachel Yarom3, Rivka Shenman3

1 Department of Environmental Health Sciences, Hadassah Academic College- Jerusalem, Israel
2 Hebrew University of Jerusalem, Israel
3 Public Health Laboratory, Ministry of Health, Haifa, Israel

Abstract- Legionella pneumophila contamination of hot water systems are particularly difficult to control due to the optimal growth conditions, protection by biofilms and the fact that chlorine and many other disinfectants are less effective at high temperatures. This paper reports on a 24 month study using an innovative method to control Legionella pneumophila in the closed loop hot water system of a major hospital in Israel, which has suffered a serious out-break of Legionnaires disease in their BMT unit. They had failed to control the Legionella infections by the conventional use of repeated shock treatments with chlorine up to 2000 ppm and by raising the water temperature to 700°C. During the period between October 2005 and May 2007 an innovative disinfectant process based on a patented, stabilized, non-toxic, taste free, bactericidal/bacteriostatic, heat resistant formulation of hydrogen peroxide containing a minute amount of oligodynamic silver (commercial name STERIL) was used to effectively disinfect the hot water system and achieve total long term control of Legionella pneumophila. The combined formulation of H2O2 and silver and other metals is some 100 times more powerful as a disinfectant than hydrogen peroxide alone and can provide a long lasting effective disinfectant residual. Our studies show that the formulation's disinfection power increases significantly as water temperature increases which contributes to its effective control of Legionalla bacteria in hot water systems which normally operate at temperatures up to 40-500°C. The silver ion deposit on the pipe walls have a bacteriostatic effect. At the end of the 24 month test period it can be stated that the stabilized H2O2-silver formulation effectively controlled Legionella pneumophila in the hospital ward's hot water system for the first time after years of chronic problems and has proved to bea promising and economical option for the long term control of Legionella bacteria in closed loop hot water systems.

Key words Legionnaires disease; control; hot water systems; hydrogen peroxide; silver; disinfection

INTRODUCTION

Legionella pneumophila contamination of hot water systems are particularly difficult to control due to fact that hot water systems, which usually operate at 40-500C provide the optimal growth conditions for Legionella. Another factor is that deposits of water hardness- calcium and magnesium-- build up, particularly in hot water systems, and provide rough, pocked surfaces and conditions for biofilms development which result in favorable conditions for the protection of bacterial infections from chemical disinfection processes. A third factor is that chlorine and some other disinfectants, which have conventionally been used, are less effective at the high temperatures typical of hot water systems. The literature reports on repeated re-infections, frequent difficulties, and problems in controlling Legionella infections in general and particularly in hot water systems (Association of Water Technologies-AWT, 2003) .

Several Legionnaires disease outbreaks have occurred in hospitals and hotels in Israel and a survey by the Ministry of Health detected Legionella bacteria in the hot water systems in 10 out of 12 hospitals in various parts of the country (Yaron and Sheinman, 1999). Despite efforts to control the Legionella infections few have been effective for long periods. This paper reports on a 24 month pilot study using an innovative method to control Legionella pneumophila in the closed loop hot water system of Rambam Hospital- a major hospital in the north of Israel, which has suffered a serious nosocomial out-break of Legionnaires' disease in its Bone Marrow Transplantation- BMT unit- one of the most sensitive units in the hospital (Oren, et al 2002)

The hospital has taken the lead in Israel and has made many determined efforts over the last 15 years to control the Legionella infections of its hot water system, but had failed to achieve adequate control by the conventional use of repeated shock treatments with chlorine up to 2000 ppm or by raising the water temperature to 700°C. These procedures achieved only limited control for a few weeks or months only. Constant operation of the hot water system at 500°C ,which is a temperature which can inactive the Legionella bacteria, was not recommended due to the danger of scalding.

LEGIONNAIRES DISEASE IN ISRAEL

Professor Hillel Bercovier of the Hebrew University of Jerusalem (HU) (Bercovier et al, 1984) reported on the first fatal case of Legionnaires disease in Israel in 1984 some eight years after Legionnaires disease was first detected in Philadelphia and described as being acquired by inhalation of aerosols containing Legionella (Fraser et al, 1977). In our field studies we isolated 39 strains of Legionella, mainly L. pneumophila, from 302 samples taken from 55 natural water sources throughout the country including the Jordan River, Lake Kinneret, ground water and irrigation systems which confirms that the pathogen is ubiquitous in Israel (Shuval, Fattal and Bercovier, 1988). We were concerned about the possible transmission of Legionella bacteria in aerosols generated by sprinkler irrigation which is widely practiced in the country. We carried out a survey of 2410 blood sera specimens taken from 1335 agricultural workers in 30 different agricultural communities. The sample included 419 water contact-irrigation workers directly exposed to aerosols from sprinkler irrigation. The control group was made up of residents in the same agricultural communities not directly exposed to irrigation generated aerosols. We found that the irrigation-aerosol exposed workers carried anti-bodies to Legionella pneumophilia seven times more frequently than the non-water contact control group (2.8% vs 0.4%)(Shuval, Fattal and Bercovier, 1988).

We concluded that with Legionella spp ubiquitous in irrigation water sources, agricultural workers exposed to sprinkler irrigation have a high occupational risk of infection with Legionnaires disease bacteria. Despite this, there were no reported clinical cases of the disease among this population group who are mainly young, healthy men with a known low susceptibility to clinical cases of the disease. However the sources of water used for agricultural irrigation in Israel are generally the same sources supplied to urban areas, hospitals, hotels, factories and the like, thus suggesting that there is a potential for Legionnaires disease transmission to more sensitive and susceptible groups. Thus, the known or reported outbreaks of the disease may be the tip of the iceberg indicating that there is a need to introduce effective methods of Legionella control in hospitals, hotels and public institutions.

LEGIONNELA CONTROL AT THE RAMBAM HOSPITAL IN HAIFA

Methods

During the course of the period between October 2005 and September 2007 an innovative disinfection process using a patented1, stabilized, non-toxic, taste free, bactericidal/ bacteriostatic, heat resistant formulation of hydrogen peroxide containing a minute amount of oligodynamic silver (commercial name STERIL also sold under other names in some countries) was used to effectively disinfect the hot water system and achieve total control of Legionella pneumophila.

Based on the approval of the Ministry of Health the following disinfection regime was introduced in the closed loop hot water system of the hospital's 50 bed BMT ward. The control treatment included two stages: A first stage, initial shock dose of the formulation which provided a 500 ppm concentration of H2O2. After a few hours this initial shock dose was totally flushed out of the system. Shower heads, hot water faucets and other end-of-the-line plumbing fixtures were disinfected in 4% H2O2 solutions of the formulation. There were no residual odor or taste problems as occur when high doses of chlorine are used. The second stage included automatic continuous feeding, monitoring and control of the formulation into the ward's closed hot water system at a dose of 20 ppm of H2O2 and a minute concentration of silver for a few hours each day. The concentration of disinfectant was monitored and controlled continuously by a specially designed1 automatic system. At the initiative of the hospital the control procedure was also introduced in the Oncology Department where positive tests for Legionella were revealed.

Laboratory test methods for Legionella Water samples drawn in 500 ml sterile containers, with 0.5 ml thiosulfate, were tested for Legionella species at monthly intervals in the hospital's laboratory or assayed in the Ministry of Health Public Health Laboratory in Haifa, using officially approved methods for Legionella testing. Water samples were concentrated by filtration and inoculated on buffered charcoal yeast extract (BCYE) plates. Plates were examined daily for growth. Suspected colonies, were sub-cultured on to fresh BCYE agar and confirmed as Legionella species by species-specific anti-sera (Edelstein, 2000; Barbaree et al, 1988).

Prior to the initiation of the control program Legionella species were frequently detected in water samples drawn from various sites in the hospital in concentrations ranging form 20 to 1400 cfu/100 ml. The hospital initiated various control programs including superheating the hot water tanks to 700°C and shock treatment with chlorine doses up to 2000 ppm. With these procedures Legionella species were eliminated temporarily and reemerged in low concentration up to 20 cfu/100ml.(Oren et al, 2002).

RESULTS

During the 24 month study period all tests for Legionella bacteria in the hot water system of both departments were negative except for one single positive sample detected after 10 months at a dead end pipe which was then corrected and put into the closed loop flow. As a precaution, a limited scale, shock treatment cycle was repeated in the infected area only. At the end of the 24 month test period it can be stated that the stabilized H2O2-silver formulation effectively controlled Legionella pneumophila in both of the hospital ward's hot water systems for the first time after years of chronic problems.

DISCUSSION

Evaluation of Alternative Legionella Disinfectants:

There are many problems in achieving effective disinfection of hot water systems to control Legionella. Few of the conventional disinfectants have been shown to have long term efficacy, particularly in hot water systems which serve as one of the main foci of Legionella multiplication and dissemination. The optimum amplification range of Legionella is a narrow band of 300°C to 400C. Above 450°C Legionella is killed with time and at 500°C it may take up to two hours to attain a 90% kill, while at 700°C a 100% kill is rapid. However, it must be pointed out that at temperatures above 45-500°C in the hot water supply system used by consumers, such as in hospitals or hotels there is a serious danger of scalding. There is also a problem of pipe corrosion and energy costs are high. Thus this method has serious constraints.

The Association of Water Technologies-AWT (2003) has published an evaluation of the alternative Legionella disinfection technologies, summarized in brief below:

Heat-and-flush (heat shock) Raising the hot water tank temperature to 60-700°C - Thermal eradication provides only temporary results: it is very labor intensive, presents scalding risks, has associated high energy costs and corrosion problems, is difficult to achieve complete effectiveness and at best provides only short term (weeks to months) effectiveness.

Chlorination Shock treatment at 20 to 500 ppm provide only temporary results and is corrosive to pipes. Produces potentially carcinogenic DBP's. Continuous chlorination at 1-2 ppm is not effective. Chlorine is significantly less effective in hot water systems which are the main foci of Legionella proliferation.

Ultraviolet (UV) RadiationProvides point of source disinfection only, but no residual and thus not effective for systems already contaminated. High energy costs and requires very clean water with low turbidity and suspended solids.

Ozonation Similar limitations as UV.

Copper-Silver ionizationEffective treatment with residual, but high initial equipment cost. Hard water and pH higher than 8 may limit effectiveness and may increase costs. Health restrictions on copper and/or silver in drinking water may limit use. Problems of corrosiveness.

Chlorine DioxideEffective treatment, however, it must be generated onsite and commercially available treatment plant costs for small scale systems such as hospitals and hotels are high. This method, while effective involves possible health risks and has been disallowed in some countries.

Mono-ChloramineMore effective in municipal systems than chlorine and fewer DBP's but like chlorine has reduced efficacy at high temperature of hot water systems which are the major foci for Legionella.

Unique Qualities of the Stabilized Hydrogen Peroxide-Silver Disinfectant Formulation

Tests have shown that this specific formulation is effective in inactivating Legionella at the concentrations recommended for use in this study. Our studies at HU have shown that the combined formulation of H2O2 and silver and other metals is some 100 times more powerful as a disinfectant than hydrogen peroxide alone and can provide a long lasting effective disinfectant residual of many days and weeks (Shuval,1999). Our research has revealed that the potentiation action of the two chemicals working in combination is basically the result of a two stage biological effect on the bacterial cell wall rather than the result of the formation of some new more potent chemical form ( Pehahzur, Shuval and Ulizur, 1997) as had been previously hypothesized.

While the disinfection ability of chlorine is seriously reduced in hot water systems, our investigations have shown that the H2O2-silver formulation is heat stable to high temperatures and it's disinfection power increases significantly as water temperature increases.At water temperatures of 380C there is an increased rate of bacterial inactivation by a factor of well over 100 than that achieved at 180 C (Pedahzur et al, 2000). This is an important feature of the formulation which contributes to its effective control of Legionella bacteria in hot water systems which normally operate at temperatures up to 40-500 C. Our studies also have indicated that the long term efficacy of the disinfectant is partially due to the bacteriostatic effect of the small amounts of silver which deposit on the walls of the piping system or tanks, and coat sediments and biofilms. We have hypothesized that the positive metal ions bond to the negative bacterial cell walls sites, disrupting membrane structure which leads to bacterial cellular death aided by H2O2 penetration.

Recent research reports have revealed that silver ions are effectively used in several medical applications which take advantage of the nanoscale silver particles which have so much surface area that small concentrations are effective antiseptics. It has been reported that the surface binding performance of the silver particles blocks the formation of a thick carpet of bacterial biofilm and is a key to avoiding infections according to Dr. Dennis Maki, Professor of Medicine and the head of infectious diseases at the University of Wisconsin Medical School ( New York Times- December 20 2005).

The Acceptability of the Disinfectant Formulation for Treatment of Drinking Water

As to the acceptability of the formulation for use as a disinfectant in drinking water systems in hospitals and hotels from a toxicological point of view: The active ingredients of the commercial disinfectant formulation under study are non-toxic H2O2 and silver. H2O2 has been approved for drinking water disinfection at the concentration required for this anti-Legionella treatment in Europe under "European Standard- EN 902–1999 - Chemicals used for treatment of water intended for human consumption-hydrogen peroxide".The use of silver at the concentration required for drinking water disinfection has been approved by the WHO, the EU and the United States Environmental Protection Agency. The commercial formulation (commercial name STERIL, also sold as SANOSIL in some countries1) has been specifically approved for drinking water disinfection by the health authorities in Australia and some other countries.The product has also been approved for Legionella control under the regime used in this study by the Israel Ministry of Health1.

SUMMARY AND CONCLUSIONS

From the results of this full scale 24 month field test in a 50 bed hospital ward, it can be concluded that the procedure reported upon here, based on the use of a stabilized formulation of hydrogen peroxide containing a minute amount of oligodynamic silver is a promising and economical option for the effective long term control of Legionella bacteria in closed loop hot water systems of hospitals, hotels and similar institutions. The non-toxic , taste free and heat stable, bactericidal/bactiostatic formulation studied has the unique qualities of providing an effective long lasting disinfection residual in piping systems and an increase of disinfection power in hot water systems making it particularly effective in the control of Legionella in such institutions.

ACKNOWLEGEMENTS

This study was carried out under the sponsorship of Swissteril Water Purification Ltd, Haifa, Israel (email - alon.one@gmail.com or alon@y-lehrer-eng.co.il) in cooperation with the appropriate authorities and staff of the Rambam hospital and the Ministry of Health, Public Health Laboratory, Haifa. Mr. Alon Lehrer and Mr. Nimrod Ben-Yehuda of the Swissteril management planned, designed, installed and operated the special disinfection feed, and control system. Additional financing for certain phases of the study were provided by the US Environmental Protection Agency-EPA and the Research Division of the European Union.

1For further information contact the company.

REFERENCES

Association of Water Technologies-AWT(2003), LEGIONELLA 2003: An Update and Statement The Association of Water Technologies , Rockville MD, Website www.awt.org

Barbaree, J.M, Morill, W.E. and Fields, B.S. (1988) Detection and recovery of legionella in water, Toxicity Assessment 3:479-490

Bercovier, H. Israeli, A. Goodman, A. and Shapiro, M. (1984) Isolation of Legionella pneumophila serogroup 1 from a fatal case of pneumonia in Israel. Isr. J. Med. Sci., 20:1109-1111

Edelstein, P.H. (2000) Legionella, in Lannette, EH, Balows A, Hausler WJJ, andShadomy HJ, (Eds) Manuel of Clinical Microbiology, 4th edn. American Society of Microbiology: Washington, DC pp 373-381

Fraser, D.W. Tasi, T.R. and Orenstien, W. (1977) Legionaires disease: description of an epidemic of pneumonia. New Engl J Med 297:1189-1197.

Oren, I. Zukerman, T. Avivi, I. Finkelstein, R. Yigla, M. and Rowe, J.M. (2002) Nosocomial outbreak of Legionella pneumophila serogroup 3 pneumonia in a new bone marrow transplant unit: evaluation, treatment and control. Bone Marrow Transplantation, 30: 175-179

Shuval, H. Fattal, B. and Bercovier, H. (1989) Legionnaires disease and the water environment in Israel. Wat. Sci Tech. 20: 11-12-

Shuval, H. (1999) Stabilized formulation of hydrogen peroxide with silver: a secondary disinfectant- in Safe Drinking Water in Small Systems: Technology, Operation and Economics. Ed. J. A. Cotruvio, G.F. Craun and N. Hearne-Lewis Publishers, New York.

Yarom, R. and Sheinman, R. (1999) Contamination of Legionella pneumophila in hot water distribution systems in hospitals across Israel- Proc. 7th Int. Conf. of Israel Society of Ecology and Environmental
Quality Sciences- ISEEQS-Tel Aviv

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