Hospital-acquired Legionnaires' disease and its preventive measures

Hospital-acquired Legionnaires' disease and its preventive measures

　　Miguel Sabria and Victor Yu

Abstract: Since the first outbreak of Legionnaires'disease in 1976, many hospitals have reported hospital-acquired Legionnaires'disease (hospital-aquired Legionnaires'disease). Although the first reported source of transmission was cooling towers, the final investigation after many hospital outbreaks over the years concluded that the source of environmental infection was almost all piped drinking water (Potable water). The main form of transmission of hospital-acquired Legionnaires' disease is inhalation of carrier aerosols; showerhead showers are not a form of transmission. Because the clinical manifestations of the disease do not have characteristic symptoms, it is necessary to do specific laboratory tests to confirm. So the disease is easily missed. When one case of hospital-acquired Legionnaires' disease is detected, it is a sign that there are more undetected cases. Routine Legionella culture in hospital water supplies has been shown to be an important strategy to prevent the disease. The long-term presence of Legionella in hospital water supplies increases doctors' suspicion of suspected cases of Legionnaires' disease, so laboratory tests are done to confirm the diagnosis and help detect patients. Legionella bacteria are often present in the water supply of hospital buildings for a long time and preventive measures are recommended, but the results of these measures are not satisfactory. The copper-silver ion system is a long-term effective sterilization method for hospital water supply. Finally, it is necessary to educate the public through the media that those hospitals that can detect Legionnaires' disease are trustworthy.

History of hospital-acquired Legionnaires' disease: After the discovery of Legionella and Legionnaires' disease, it was recognized that Legionella is also an important cause of hospital-acquired pneumonia [1-7]. In 1965, the first documented outbreak of acquired Legionnaires' disease occurred at the Washington Psychiatric Hospital in the United States, with 81 cases of pneumonia and 15 deaths. Retrospective serum antibody examination confirmed that 85% of patients were positive [8]. The largest hospital outbreak occurred at the Wadsworth Veterans Medical Center (VAMC) in Rocky Mountain, USA, with 218 confirmed cases from 1977-1982. Since then, the occurrence and outbreak of hospital-acquired Legionnaires' disease have been reported in more than 300 papers.

Form of transmission: Initially, when the Centers for Disease Control (CDC) isolated Legionella bacteria from the air-conditioning cooling tower water near the hospital and confirmed that the aerosol produced by it could reach the vicinity of the patient, it was considered that the cooling tower was the source of infection [10]. But at that time it was not known that Legionella could survive in the water supply pipeline for a long time; and epidemiological investigations also proved that Legionnaires' disease also occurred in the edge area of the hospital, where cooling tower aerosols could not reach; and there was no Legionella test at that time. Collect pipeline water supply.

The 1982-1985 investigation found that the presence of Legionella in drinking pipeline water and the supply of drinking water were the real source of Legionnaires' disease (the number of Legionella in the biofilm of the bacteria in the hot water system can reach 104-105/cm2 and can last for several months)[11-13]. Since then, reports of Legionnaires' disease in cooling towers have disappeared. From the hundreds of hospital-acquired Legionnaires' disease literature since 1985, except for one due to air conditioning cooling tower water [14] (and this work needs further investigation), other hospital-acquired Legionnaires' disease occurrence and outbreak are caused by drinking water.

In three well-known outbreaks of this disease, including VAMC in Wadsworth, Burlington Hospital in Vermont and Rhode Island Hospital, epidemiological investigations at the time believed that air-conditioning cooling towers were the source of infection, but despite the continuous disinfection of their cooling towers by all three hospitals, hospital-acquired Legionnaires' disease still occurred again. Subsequently, copper-silver ion pipeline facilities were installed in VAMC in Wadsworth and Burlington hospitals in Vermont to solve the problem. Further investigation at Rhode Island Hospital confirmed that the patient's molecular subtype of Legionella was consistent with the molecular subtype of Legionella in air-conditioning cooling towers; however, subsequent investigations also confirmed that the molecular subtype of Legionella in drinking water systems was also of the same type. Although the cooling tower continued to disinfect, an outbreak of the disease occurred again in the hospital a year later. [17]. Drinking water is also isolated at this time. A few years later 'Mermed' et al.[18] confirmed that 'although Legionella has not been isolated from the cooling tower of Rhode Island Hospital, 'hospital-acquired Legionnaires' continues to occur. Molecular subtyping of Legion strains isolated from clinical and environmental sources confirmed that the hospital water supply was the source of infection. It can therefore be assumed that almost all cases of this disease are contaminated by hospital drinking water.

Inhalation of Legionella is now known to be the main mode of transmission of hospital-acquired legionellosis [2'19-24]. Legionella has been reported to reside in the oropharynx [25]; this has not been confirmed by others [26]. A pre-delirium study of 'aspirator complications' after tumor resection in patients with head and neck cancer confirms that '30% of postoperative pneumonia is due to Legionella pneumophila [13].

Showers are often mistakenly thought of as a mode of transmission. The authors report a retrospective analysis of showers in three hospitals to show the relationship with showers, and the results did not confirm that the disease was related to showers [27]. Neither retrospective studies [28'29] nor prospective studies have been able to confirm this relationship [2'30]. Later reports even suggested that showering could prevent Legionnaires' disease [22.31]. The reason for these conflicting findings may be that patients are able to walk while showering and therefore use less aspirators. Therefore our transplant center allows patients to shower' against the practice of banning showers due to panic legionellosis.

Legionnaires' disease has been associated with aerosol-generating devices using tap water in hospitals [32-34]'but these reported aerosol intensities vary. For example, at the University of Chicago Hospital, the application of water contaminated with Legionella bacteria through a jet nebulizer directly into the respiratory tract of patients is an obvious risk factor for hospital acquisition of Legionnaires' disease [35]. Another. Some reports of nasogastric tube [21'22'36] and laryngeal tube insertion [2'37] associated with hospital acquisition of Legionnaires' The authors speculate that aerosol inhalation of contaminated water is the method of transmission of the disease.

Missed diagnosis of hospital-acquired Legionnaires' disease: The susceptibility to missed diagnosis of hospital-acquired Legionnaires' disease is a major bias in calculating its incidence. Correct diagnosis requires laboratory testing of Legionnaires' disease because its clinical manifestations are not without specific symptoms. The hospital incidence of Legionnaires' disease in the United States has been controversial. Due to the clinical manifestations of non-specific diagnosis rely on laboratory methods. Only 253 (19%) hospitals in the United States participate in the CDC National Hospital Infectious Disease Surveillance System and routinely perform hospital-acquired Legionnaires' disease testing in high-risk patients [38]. And only 21% of hospitals have experience testing for Legionella in respiratory specimens from pneumonia patients. In Catalonia Spain, only 25% of hospitals do Legionella culture for hospital-acquired Legionella disease; and only 10% of cases do Legionella urine antigen testing [39]. In the same survey, only one hospital was able to fully complete the Legionella test program for all cases under surveillance. As a result, a large number of hospital-acquired Legionnaires' disease are missed.

The term used when the disease broke out in the 1980 s was "sporadic", "epidemic" and "highly epidemic" to quantitatively describe the number of Legionnaires' disease, rather than an outbreak. Now realize,. Because drinking water has been found to be a source of infection', many hospital-acquired Legionnaires' disease may be missed [2'40'41] and outbreak is a better term to describe more accurately and better reflect the intensity of the disease. When only one patient with hospital-acquired Legionella is found, it can be an important signal that there are other undetected cases [40]. In a series of hospital outbreaks of hospital-acquired Legion cases, pediatric hospitals were also included [42-50]. All outbreaks were due to contamination of the hospital's water supply.

Risk factors for hospital-acquired Legionnaires' disease: Wasting disease is the main risk factor for this disease. Patients with chronic lung disease or surgery under general anesthesia are at greater risk because the main form of transmission is inhalation of Legionella. Organ transplants, especially heart transplants, have the highest risk [51-53]; bone marrow transplants have the lowest incidence of this disease. Non-pneumophila Legionella species, particularly Legionella Mikedade, are frequently associated with bone marrow transplant recipients [55-57]. It is another risk factor when treated with bordesone. AIDS does not appear to increase the risk of the disease [59-61].

Clinical manifestations: Legionnaires' disease has no specific clinical manifestations [62-65]. Diarrhea, neurological symptoms, unconsciousness and high fever above 39°C, as well as sodium reduction, abnormal liver function and hematuria may occur [66,67]. Community-acquired Legionnaires' disease has more severe clinical manifestations than hospital-acquired Legionnaires' disease, with more prominent gastrointestinal and neurological symptoms [66]. This may be related to delayed diagnosis and delayed use of antibiotics in the community. Early hospital-acquired Legionella mortality rates are as high as 80%, usually because immunosuppressed patients do not receive appropriate antibiotics [68]. However, the mortality rate in the United States decreased from 46 per cent in 1982 to 14 per cent in 1998. This is associated with increased awareness and empirical treatment of hospital-acquired pneumonia with quinolones [69]. Factors such as virulence of the strain [70,71]; delay in antibiotic therapy [72,73]; and degree of immunosuppression are all associated with mortality [69,74].

Laboratory diagnosis of Legionnaires' disease: The diagnosis of Legionnaires' disease requires bacterial culture, but Legionella does not grow on standard bacterial media in most hospitals, and special selective media must be used. Unfortunately, hospitals do not routinely do this for patients with pneumonia [38]. The best culture medium for Legionella consists of BCYE-alpha agar supplemented with a variety of antibiotics or dyes [75,76], the addition of which can facilitate the observation of colonies [. Pretreatment with acid or heat inhibits overgrowth of the microflora [77 '78]. The sensitivity for detection of Legionella using various media and pretreatments was 80% and the specificity was 100. Cultures of respiratory specimens should be routine in all hospitals where Legionella is present in the water supply. The isolated Legionella can also be used for molecular subtyping by DNA methods to establish an epidemiological link with water sources. Detection of urinary antigens has become the most widely used method for early diagnosis of Legionnaires' disease [79,80], with positivity disappearing within 2 months. Patients who have received immunosuppressive therapy with cortisone have a longer positive period [81]. Concentration of urine specimens increases the sensitivity of the test [82]. The main limitation of the urine antigen test is that it can only detect soluble antigens of Legionella serotype 1. Serotype 1 of Legionnaires' disease accounts for 92% of community cases and 80% of hospital cases [83]. Legionella pneumophila serotype 1 did not cross-react with other serotypes. The commercial ELISA kit for Legionnaires' disease serotype 1 has a sensitivity of approximately 70% and a specificity of 99%(Binax 'Portland' USA;Biotest 'Dreieich' Germany ; and Bartels' Washington' USA). Rapid immunochromatographic assay reagents are now commercially available (Binax NowUSA) [79]. This test is similar in sensitivity and specificity to ELISA [84], but faster than ELISA (15 minutes VS2-3 hours) makes it particularly useful for small laboratories.

Direct immunofluorescence (DFA) is a rapid diagnostic method that makes legionella visible in samples [75]. But there must be a lot of Legionella. Legionnaires' disease is confirmed when there is a 4-fold increase in serum antibodies. The peak of IgG and IgM seroconversion occurs on the 90th day of onset, so there may be no significant change in serum titers during the 4-6 week recovery period [85]. Serological tests are useful for epidemiological investigations, but their application in clinical practice is limited. The specificity of serological testing in reference laboratories is as high as 96%, but the results of inexperienced laboratories are unstable.

Molecular subtyping has proved useful in determining the source of Legionnaires' disease, and its techniques include monoclonal antibody typing, plasmid analysis, outer membrane protein profiling, endonuclease analysis, and various PCR methods [86],. However, the results must be consistent with epidemiological data [87 '88].

Routine environmental culture of Legionella in hospitals: Routine culture of Legionella in hospital environmental water has become an effective strategy for the prevention of hospital-acquired Legionnaires' disease. If Legionella is present in the hospital water supply for a long time, the likelihood that doctors will consider Legionella as the cause of hospital-acquired pneumonia increases. Therefore, it needs to be verified by laboratory methods, especially sputum culture. While environmental cultivation has proven valuable, concerns about the negative reputation of the media have become an obstacle to the adoption of this approach.

The CDC recommends that environmental cultures be performed only when cases of hospital-acquired Legionnaires' disease are identified. Many European countries have adopted this approach [89]-such as the United Kingdom, Wales [90], Italy [91], Switzerland [92] and Spain [93]. It is the official intent, not the scientific data, that drives this passive regulation. Some literature states that when Legionella was already present in the water supply, Legionella laboratory tests were initiated to monitor all patients with hospital-acquired pneumonia. In this way, hospital-acquired Legionnaires' disease can be found [13'39'41'56'94-97]. The QUOTE guidelines dictate that hospitals do routine environmental cultures of Legionella. This has been done in Allegheng County [98] and Maryland [99] in the United States, Cataloria, Spain [100], France [101] and Denmark [102].

Antibiotic therapy: Newer macrolides and quinolones, now used as the first choice for the treatment of Legionnaires' disease. Erythromycin is no longer used because of venous infiltration and relatively high gastrointestinal side effects. Fluorinated quinolones and azithromycin have the greatest anti-Legionella effect in cells and in animal models [103 '104]. There has been a history of relapse of Legionnaires' disease when treated with erythromycin and a longer fever-free period and more clinical complications when compared with fluoroquinolones [105].

Control of Legionella in hospital water supplies: Sterilization of water supplies is often recommended as a key factor in the control of Legionella growth. However, it has little effect on the Legionella community in practice [106]. The only way to intervene with Legionella is to maintain the temperature in the hot water tank at 50-60°C. However, a wide range of disinfection should be carried out before increasing the temperature of the hot water, otherwise even if this is done, the effect is very small.

In the event of an outbreak of Legionnaires' disease, emergency methods can be used, including hyperchlorination in combination with hyperthermia and flushing [107]. The disadvantage is that it is labor-intensive and has only a short-term effect (the legion can have another colony for weeks to months)[108]. Continued high chlorination is disadvantageous because of the high cost, poor effectiveness, corrosion of pipes and the release of carcinogenic by-products into drinking water [107]. The copper-silver ion system has been used in Spain and the United States, and there are more than 200 devices in the world. Sixteen units in the United States have been in use for 5-11 years [109]. Other promising methods have been identified including chlorine dioxide and monochloramine, but the final results may be years away.

Political considerations: Legionnaires' disease is a high-profile disease with political influence over scientific information. An outbreak of hospital-acquired Legionnaires' disease can have a negative impact on hospitals, reducing the number of patients and being blamed for medical errors. The public does not recognize Legionella as a common parasite in artificial water supply systems. The incorrect assumption of the media is the cause of the wrong influence on the public. The European Pompidou Hospital in Paris, which had 12 cases of hospital-acquired Legionnaires' disease in an eight-month period, was heavily criticized by the media for its lack of expertise [110]. We believe that the condemnation of the Pompidou hospital is unfair. A hospital with knowledgeable physicians and a laboratory capable of legionella can prove to provide excellent care. Such hospitals and physicians should be praised, not slandered. Other hospitals cannot diagnose cases of Legionnaires' disease, and deaths from hospital-acquired Legionnaires' disease are attributed to other causes resulting in incorrect results to the detriment of the public. Public health agencies must play an active role in protecting hospitals from the detection of Legionnaires' disease. Fear of media exposure and litigation prevents the most effective prevention and treatment of hospital-acquired legionellosis.

　　译自 THE LANCET Infectious Diseases Vol 2 June 2002;P.368-373

(Translated by Li Peicheng and Chen Changyi, Chen Changyi School)

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