Leech management before application on patient: a nationwide survey of practices in French university hospitals

Leech storage before use and delivery

This national survey showed that nearly 70% of the French University Hospitals use leech therapy, confirming a wide use of this recent practice. Mostly, leeches are stored in the pharmacy department, which enables a better control of leech management prior to delivery and to application. This includes a centralized maintenance, a controlled traceability and an easier surveillance in case of nosocomial infection related to leech therapy. Sartor et al. suggested that storage conditions and quality of water could increase the risk of contamination related to the leeches. When leeches, delivered initially by the pharmacy, were stored in the hand surgery unit in an aquarium that was not regularly decontaminated, infections were twice as common (4.1% vs 2.4% respectively) as in the reconstructive units that received leeches directly from the pharmacy before use. This observation led the authors to recommend maintaining leeches at a central site, with strict protocols of cleaning and disinfection of the aquariums [6].

From our experience, a centralized leech storage and delivery is obviously the best practice to recommend, in agreement with American, English and German Guidelines [12, 13, 14].

Leech delivery was registered in only 56.5% of the cases on a database in the pharmacy and was nominative per patient, while 7 centers practiced a global delivery to the medical or surgical units. Despite the lack of guidelines, we consider that leech should be nominally delivered and batch number recorded, in order to allow optimal investigation in case of healthcare-associated infection related to leech therapy. Overall and in a safer way, the delivery must be limited to a single use only and then discarded to avoid any risk of infection transmission between patients, as suggested in the protocol for the use of leeches by some authors [16, 17].

Microbiological controls prior leech use

There is no guideline concerning either the need or the procedure of an environmental surveillance culture of leech tank water. Wilmer et al. advocated microbiological surveillance in routine to establish the ecology of water, arguing that identifying resistant organisms would allow clinicians to adjust ATBP regimens [18]. With the aim to limit serious wound infections, Verriere et al. are also in favor to perform microbiological controls of the water tank, allowing to detect resistant strains, to discard the corresponding leeches and to select an appropriate ATBP [19]. However, the finding of only susceptible isolates does not preclude the presence of resistant isolates that would be present at low density in the leech crop and would remained undetected. The level of evidence is to date too poor to recommend to implement such policy. It is not established that either the results of microbiological analysis of water tank or leech microbiota would accurately predict the bacteria involved in infection following leech therapy. Indeed, data suggest that the leech gut microbiota is more complex than initially thought [20] and includes many distinct Aeromonas strains. In addition, host-leech-microbiota is a complex biological system that must not be ignored in which the dominant strain(s) in the leech gut or in the tank water is not always the dominant strain in the water tank or the pathogenic strain in the patient. Until a greater body of evidence including a cost effectiveness analysis, it is tricky to recommend a systematic microbiological control to predict leech safety or to adapt prophylactic antimicrobial treatment.

Antibiotic prophylactic treatment

Despite the numerous publications widely showing the interest of ATBP during leech therapy [15, 19, 21, 22], ATBP was prescribed in only 40% of the French hospitals interviewed. Overall, this result, together with the worrying percentage of no response (6 centers, 26%), suggests that the frequency and severity of this nosocomial infection is underrated by clinicians, as demonstrated elsewhere [21]. Most of authors suggest to start ATBP prior or when starting the application of leeches on patient, to administer antibiotics during all the duration of the leech therapy, and to end it 24 h after the end of leech application [7, 16]. Lineaweaver et al. suggested to extend ATBP until cicatrization has occurred [10]. Consensual guidelines on ATBP associated with the use of leeches are needed. Antibiotics the most frequently encountered in protocols of ATBP associated with leech therapy are fluoroquinolones, sulfamethoxazole/trimethoprim and third generation cephalosporins [7, 21], although several authors have reported since 2012 the emergence of Aeromonas resistant strains, particularly to ciprofloxacin [16, 23, 24, 25]. Amoxicillin/Clavulanic acid should be avoided because aeromonads are virtually all resistant to this antimicrobial agent because oxacillinase and/or cephalosporinase is expressed by the vast majority of aeromonads [26, 27, 28]. In our center, all prescribers of medicinal leeches are informed on the risk of infection related to leech therapy, and are advised on prophylactic treatment by a letter systematically accompanying leech delivery.

Other approaches for controlling the risk of infection

In order to reduce the risk of infection related to leech therapy, alternatives to ATBP have been described. Mackay et al. tried to sterilize the leech gut of pathogens by immersing leeches in an antibiotic solution during 12 h [29]. Mumcuoglu et al. proposed to eliminate Aeromonas sp. of the leech digestive tract by feeding them with an arginine solution supplemented with ciprofloxacin. All these attempts were unsuccessful [30]. Such approach should be strongly discouraged because of the risk of selecting resistant mutants (e.g., to ciprofloxacin). Alternatively, further research is required to identify new strategies for removing the aeromonads or at least drastically decreasing their density from leech gut, but the objective is obviously difficult to achieve because of the obligate symbiosis between leech and aeromonads.

We show here that 39% of the French hospitals perform an external decontamination, among which 77.7% used chlorhexidine. Bauters et al. described similar practices of decontamination in a Belgian hospital, treating leeches with chlorhexidine 0.02% during 15 s, followed by successive rinses with sterile water [31]. Comprehensively, the level of evidence is rather low to identify the best practice, and there is consequently no consensus on the optimal method to use. Further study that improves knowledge on this point should be welcomed, but the principle of an external decontamination ensuring a nearly germ-free state during few hours and preserving the suckle capability of the leech should reasonably be recommended [32]. Indeed, flaps or (re) implanted tissues are associated with a local immunosuppression, and the wound caused by the jaws of the leech offers a cutaneous entry point by contiguity. In a general way, a consensual approach is needed with at least European or even international Guidelines [8].

Legal status of medicinal leeches

Leech is a strikingly unparalleled product in healthcare practice, so that the legal status was not, until recently, clearly established. Many countries experienced the need to regulate for health safety purposes, and this resulted in diverse status: the French National Agency for Medicines and Health Products Safety (ANSM) conferred to medicinal leeches the status of therapeutic aid; the United States Food and Drug Administration (FDA) the status of a medical device, approved in 2004 [33]; in the UK, the Medicines and Healthcare Products Regulatory Agency (MHRA) conferred the status of a medicinal product when leeches are used with an obvious medical purpose [34], and the German Federal Institute for Drugs and Medical devices (BfArM) conferred to starved leeches, the status of drug since 2008 [14]. German recommend specifically a quarantine storage to starve leeches during at least 32 weeks after the last feed. Although the level of scientific evidence is not established for preventing the risk of infection to Aeromonas, it likely controls potential viral risks.