Aeromonas Infection After Medicinal Leech Therapy: Case Reports and Review of the Literature

Abstract

Medicinal leech use has become a common means for treatment of vascular congestion after plastic and reconstructive surgery, but leech therapy can be a source of infection as well. Such infections are typically caused by Aeromonas species. We present two cases of Aeromonas infection after leech therapy and review the features of other reported cases. Manifestations of Aeromonas infection after leech use can range from mild local infection to septic shock. A combination of debridement of the infected tissue and antibiotic administration, usually with a third-generation cephalosporin or fluoroquinolone, often leads to cure of the infection, but the rate of flap or replantation loss is high. Issues regarding prophylactic use of antimicrobial agents to prevent infection are discussed. The use of medicinal leeches has become an accepted method for salvaging tissues with vascular congestion after surgical procedures involving tissue flaps or replantations [1–4]. Aside from excessive bleeding, wound infection is the most frequent complication of leech therapy [1]. Leech-related “erysipelas” was recognized and described as early as the 19th century [3]. Whitlock et al. [5] first reported the possibility of infection caused by Aeromonas from leech use after culturing A. hydrophila from the most commonly used species of medicinal leech, Hirudo medicinalis. Although there were no confirmed cases of Aeromonas infection associated with leech use at that time, the authors warned against the therapeutic use of leeches because of the theoretical risk of infection. The first case of A. hydrophila wound infection associated with the medicinal leech was described by Dickson et al. in 1984 [6]. This report described a patient who underwent leech therapy to decrease vascular congestion after breast reconstruction with an abdominal rectus flap. Discussions of infection complicating medicinal leech use have been infrequently published in the nonsurgical literature. Infectious diseases physicians should be familiar with the diagnosis and treatment of this medical problem and may face questions regarding potential preventive measures. We present two cases of Aeromonas infection caused by leech therapy and review similar cases in the English-language literature to better characterize these infections. Case Reports Case 1. A 67-year-old woman with squamous cell carcinoma of the mouth underwent anterior resection of the floor of the mouth with fibular free flap reconstruction and skin grafting. She received ampicillin-sulbactam preoperatively and for a week postoperatively. On the third day after surgery, the free flap developed vascular congestion and leech therapy was initiated and continued over the next 48 hours. There was improvement in the appearance of the flap, although 30% of the flap became nonviable. On postoperative day 14, the patient returned to the operating room for reexcision of the original surgical margins that had been positive for carcinoma. She again received ampicillin-sulbactam perioperatively. Upon exploration of the mouth, it was noted that the patient had partial necrosis of the fibular flap with pus underneath the flap and exposed bone. Cultures of the pus were obtained intraoperatively, and these yielded two strains of Aeromonas hydrophila as well as Klebsiella pneumoniae and Staphylococcus aureus. Antibiotic susceptibility testing was not performed. The flap was debrided, a new nasolabial flap was constructed, and the patient continued to receive ampicillin-sulbactam for 6 days. The surgical site ultimately healed completely. Case 2. A 73-year-old woman with rheumatoid arthritis underwent right forefoot reconstruction with first metatarsal-phalangeal arthrodesis, second through fifth hammertoe correction, and resection of the metatarsal heads (Hoffman procedure). Three doses of cefazolin were administered perioperatively. On postoperative day one, the toes appeared well vascularized, but on the second postoperative day, significant vascular congestion of the third, fourth, and fifth toes was noted. Leeches were applied over the subsequent 72 hours with improvement, but partial necrosis of the third, fourth, and fifth digits occurred. The patient underwent removal of pins stabilizing the third and fifth toes because of a concern that proximal infection of the foot might occur in the setting of distal necrosis. The patient was treated with cephalexin. On postoperative day 14, formal debridement of the foot was performed with amputation of the third, fourth, and fifth toes. Intraoperative cultures from deep tissues and bone grew three strains of A. veronii biotype sobria, coagulase-negative staphylococcus, and Enterococcus species. All Aeromonas strains were resistant to ampicillin-sulbactam but susceptible to trimethoprim-sulfamethoxazole and fluoroquinolone agents. Only one strain was resistant to cefazolin but susceptible to other cephalosporins, and another strain was resistant to aminoglycosides as well as second and third generation cephalosporins and intermediate in susceptibility to cefazolin. Cephalexin was continued, and a second debridement was repeated 1 week later because of concern over persistent infection, but deep tissue cultures from this debridement were negative for bacterial growth. The patient was treated with ciprofloxacin for a total of 8 weeks, with complete healing of the foot. Review of the Literature Additional cases of Aeromonas infection after leech therapy were identified through a MEDLINE search of literature published between January 1966 and December 2000 using the key word Aeromonas cross-referenced with the keyword “leeches.” Secondary references were also reviewed. There were reports of 24 cases in the English-language literature in 11 references [1,2,4,6–13], and 23 of these cases provided adequate clinical and microbiological data, summarized in Table 1. One reference, published only in abstract form, was excluded because of lack of data [12].TABLE 1: Reported Aeromonas infections after medicinal leech useTABLE 1: Reported Aeromonas infections after medicinal leech use (continued)Basic demographic data such as age and sex were lacking in several cases, but a wide age range for leech-related infections has been observed, from age 2 to 73 years. Serious Aeromonas infection not related to leech therapy has been associated with the presence of cirrhosis and/or malignancy as predisposing factors [14]. However, in the cases of leech-related Aeromonas infection in which information is available, approximately half of the patients were apparently previously healthy and had undergone vascular or tissue reconstructive surgery for trauma. Malignancy was present in several patients who had undergone reconstructive surgery after operations for breast, skin, or oral cancer, although no patients were reported to be receiving immunosuppressive medications. In addition, no patients were noted to have underlying chronic liver disease. All cases of Aeromonas infection except for case 2 presented above occurred after leech therapy for flap, replantation, or revascularization procedures. Signs of infection appeared from 1 to 26 days after the initial application of leeches, and in at least 11 cases, infection became manifest more than 10 days after leech therapy. A. hydrophila was the predominant species of Aeromonas isolated from the cases reviewed, although A. veronii bt sobria was identified in two patients. In most cases, Aeromonas was reported as the only infecting organism, but in four patients, additional potential pathogens were isolated. The spectrum of disease caused by Aeromonas infection included cellulitis, abscess formation, myonecrosis, and sepsis. Tissues adjacent to the area where leeches are applied appear to be at risk for infection as well, as in patient 13 who underwent leech therapy for congestion of a rectus flap to the chest and later developed an abdominal abscess at the donor site of the flap. In many cases, the presence of associated systemic symptoms was not reported. The outcome of disease in most cases was partial or complete loss of the reconstructed tissue. The series reported by Mercer [12] (patients 19 through 24) appears somewhat unusual in that most infections appeared to be clinically trivial. This has raised the question of whether these cases may actually represent colonization or contamination [2], particularly because at least one (patient 21) resolved without antibiotics. There were no deaths reported as a result of Aeromonas infection despite the fact that several patients had documented Aeromonas bacteremia (patients 3, 6, and 16). Regarding therapy, most patients underwent both debridement and treatment with antibiotics. Apparently successful antibiotic regimens included second-and thirdgeneration cephalosporins, fluoroquinolones, ampicillin-sulbactam, amoxicillin-clavulanate, trimethoprim-sulfamethoxazole, and aminoglycosides. There was often no indication whether patients were receiving prophylactic antibiotics at the time of leech therapy. However, in cases in which antibiotic prophylaxis was mentioned, it is noteworthy that agents typically given for surgical prophylaxis, such as cefazolin or cephradine, were often used and these agents are not ones to which Aeromonas is typically sensitive. Patient 1 was receiving ampicillin-sulbactam at the time leeches were placed, but Aeromonas is inconsistently sensitive to this agent (see below) and susceptibility testing on the patient’s isolates was not performed. Discussion Epidemiology. Currently, the most frequent indication for medicinal leech therapy is inoperable venous insufficiency after tissue flap or replantation procedures [1,2,10]. Leech therapy is less commonly used for the treatment of hematomas or postoperative swelling [2,10,15]. The use of leeches may prevent secondary arterial thrombosis and tissue necrosis that occur after venous congestion by removing blood from engorged tissue and maintaining perfusion until venous revascularization can be established [1]. Substances secreted into the host from the leech salivary gland include the anticoagulant hirudin, vasodilators, and proteolytic inhibitors, and these in combination with removal of blood may contribute to the beneficial effects of leech therapy in a manner that cannot be mimicked by pharmacologic agents [1,3,16]. The most common organism associated with wound infection following leech therapy is Aeromonas [5,6,13,17]. Aeromonads are gram-negative facultatively anaerobic bacilli typically found in fresh or brackish water, tap water, and soil [18]. Aeromonas species causing significant human infection include A. hydrophila, A. caviae, A. veronii bt sobria, A. veronii bt veronii, A. jandaei, and A. schubertii, and these species have been implicated in a variety of human illnesses (reviewed in [19]), most commonly gastroenteritis [14,20]. They also cause extraintestinal infection in both normal and immunocompromised hosts [21,22]. Skin and soft tissue infection are the most frequently noted extraintestinal manifestations of Aeromonas infection and typically occur in the setting of water or soil contamination of a traumatic wound [14,20,21,23]. Aeromonas has the same natural habitat as the leech, namely fresh water, and is an endosymbiont of the Hirudo medicinalis gut [5,24,25]. Aeromonas can be introduced into a human host during attachment of the leech through the immediate regurgitation of gut contents by the leech before it begins sucking [26]. Aeromonas can also be cultured from the anterior and posterior sucking parts of the leech as well as the mucus trail secreted by the leech [5]. Aeromonads are believed to aid the leech in the digestion of ingested blood, because H. medicinalis lacks certain digestive enzymes in its gut that can be supplied by the bacteria [5,24,25]. It is presumed that leech-related Aeromonas infections are caused by bacteria present in the leech digestive tract at the time of feeding. In a recent study, Graf [16] investigated the types of bacteria normally present in the leech gut. Leeches from several sources were fed a blood meal, and then the contents of the digestive tract were cultured. Graf identified only A. veronii bt sobria in the leeches and concluded this is the predominant leech symbiont. Mackay et al. [26] also found A. veronii bt sobria to be the predominant isolate in the gut of H. medicinalis. Other investigators have also found exclusively A. hydrophila [5] or unidentified Aeromonas species [24] in the digestive tract of H. medicinalis. Some authors, however, have reported the isolation of a variety of bacterial species in addition to Aeromonas from either the leech digestive tract or whole leech homogenates [26–29]. Pseudomonas and Acinetobacter species, Staphylococcus epidermidis, Enterobacteriaceae, and Flavobacterium indologenes have been identified, although it is unclear whether the source of some or all of these non-Aeromonas isolates was the leech gut or the surface of the leech, because the latter can also be colonized with bacteria [27,28]. Investigators have also found organisms other than Aeromonas in cultures of leech secretions [5] or water in which leeches are maintained [6], but the significance of these organisms is unclear and they have at times been dismissed as contaminants [5,29]. Furthermore, it appears that different species of leeches may be colonized by different types of bacteria [24,26,27,30]. In any case, there are only rare reports of wound infection caused by organisms other than Aeromonas associated with the application of leeches. Pereira et al. [31] reported a case of cellulitis caused by Serratia marcescens in a woman who received leech therapy after undergoing digit replantation. Cultures of bedside leeches and transport water also grew S. marcescens, although it is unclear whether the leech cultures came from gut contents or the surface of the leeches. New leeches from the supplier were free of Serratia. Only one additional reported case could be identified in which leech therapy was associated with infection by an organism other than Aeromonas, and this occurred in a woman who received leech therapy for vascular congestion of a tissue flap and developed infection caused by Vibrio fluvialis [17]. The organism was present in the leech storage media, and it was postulated that the Vibrio came from the leech digestive tract, although this was not confirmed. V. cholera has also been isolated from the digestive tract of H. medicinalis [26] but has not been implicated in clinical infection. Of note, the development of Aeromonas infection after leech bites in the wild appears to be extremely uncommon, if it occurs at all [32]. However, infection caused by Aeromonas has been reported to follow medicinal leech therapy at a rate of 7% [10] up to 20% [2,12]. Apparently, the presence of traumatized tissue facilitates infection by Aeromonas after a leech bite. The risk of infection appears to be increased in tissues with poor arterial blood supply, and ischemic muscle may be particularly susceptible [2,10]. It is thought that the use of leeches on injured or ischemic muscle tissue can lead to myonecrosis [2] and, for that reason, arterial insufficiency is a contraindication for the use of leech therapy [2,10,17]. As noted above, consequences of Aeromonas infection after leech therapy ranging from minor wound infection to extensive tissue loss and sepsis have occurred [8,10]. Further, it has been noted that the survival of infected tissue flaps after leech therapy is less than one-half that of uninfected flaps where leeches have been used (30% versus 60–80%) [2]. There were no deaths in the series of cases reviewed above, despite several instances of Aeromonas bacteremia. Although an uncommon cause of gram-negative sepsis, the mortality of Aeromonas bacteremia is reported to be high. In a series of Aeromonas infections identified in California, 27.3% of patients with Aeromonas bacteremia died [20], although all deaths occurred in patients with other underlying medical problems. In an earlier review of Aeromonas infections, the mortality rate of Aeromonas bacteremia was noted to be 57% [14]. Antibiotic susceptibilities and treatment. Aeromonas wound infections after leech therapy often respond to antibiotic therapy and debridement, although, as noted, the risk of tissue flap or replantation loss is considerable. Whereas prompt debridement of necrotic tissue is important, it is recommended that closure or additional reconstruction of the infected site should be delayed until resolution of the infection [10]. Regarding antibiotic therapy, investigators have tested isolates of A. hydrophila obtained from the digestive tract [29,33] and/or surface [24] of leeches against various antibiotics. These studies, as well as others using clinical isolates, have shown that, in general, aeromonads are resistant to ampicillin and first-generation cephalosporins, have variable sensitivity to secondgeneration cephalosporins, and are usually susceptible to thirdgeneration cephalosporins, aztreonam, aminoglycosides, and fluoroquinolones, with tetracycline and trimethoprim-sulfamethoxazole being active in many cases, though not all [10,27,29,33,34]. Janda et al. [35] have reported that the sensitivities of A. hydrophila, A. veronii bt sobria, and A. caviae are similar. However, a study by Burgos et al. [34] found frequent resistance of A. veronii bt sobria to amoxicillin-clavulanic acid, whereas this agent was often effective against A. hydrophila and A. caviae strains. In the study by Burgos et al., A. veronii bt sobria was also more likely to be resistant to piperacillin, ticarcillin, and trimethoprim-sulfamethoxazole than A. hydrophila and A. caviae. Prevention. Because the risk of infection after medicinal leech therapy appears to be increased in tissues suffering from arterial insufficiency, particularly ischemic muscle [2,10], a number of authors warn against the use of leeches in these circumstances [2,10,17]. The use of medicinal leeches in immunocompromised patients has also been discouraged because of the potential severity of Aeromonas infection in these patients [2,4,13]. There are no data regarding the frequency of recurrent Aeromonas infection in persons undergoing repeated episodes of leech therapy, but the risk would likely depend on a combination of several factors, including the level of immunocompromise of the host, the presence of ischemia in the tissue graft, and the presence of Aeromonas in the leech digestive tract. There are no standard guidelines regarding either the use of antibiotic prophylaxis in the setting of leech therapy or which agents may be appropriate for use. The association of Aeromonas infection with the application of medicinal leeches has led many authors to advocate the routine use of antibiotic prophylaxis when leech therapy is used [2,7,8,10,13]. The administration of antibiotics to patients undergoing leech therapy has resulted in measurable postprandial antibiotic levels in leeches and significantly reduced ability to recover Aeromonas from leech enteric cultures [36]. Antibiotics, therefore, may decrease the number of organisms introduced into a wound as well as treat organisms that do gain entry. Third-generation cephalosporins [10,29,33] and fluoroquinolone antibiotics [8,33] have been suggested as prophylactic agents because of their excellent activity against Aeromonas. However, limited information regarding the actual rate of infection after leech use has been published, and there are few data to show whether antibiotic prophylaxis is effective in preventing leech-associated infections. Many reports of leech-related infection do not comment on whether antibiotics were being given at the time of leech placement, and there are no prospective, controlled trials studying the effect of prophylactic antibiotics on infection after leech application. Lineaweaver et al. [10] commented that after seeing 3/42 patients treated with leeches develop Aeromonas infection, antibiotic prophylaxis (usually cefotaxime) was administered in an open manner to 30 subsequent patients receiving leeches and none of these patients developed Aeromonas infection. However, additional data would be useful in evaluating the success of such preventive treatment. In addition to the paucity of data supporting the routine administration of prophylactic antibiotics during leech therapy, there are also concerns regarding the use of broad prophylactic agents such as third-generation cephalosporins or fluoroquinolones and their potential to increase the prevalence of resistant organisms [27]. Investigators have instead advocated regular culturing of leeches as a guide to prophylaxis [2,27] or cleaning the surface of leeches to reduce the risk of infection [11,16], although these approaches do not have demonstrated efficacy. Furthermore, studies have shown that incubating leeches in a solution containing tetracycline or cefoperazone is not effective in sterilizing the leech digestive tract [26], and immersing leeches in nonlethal concentrations of ethanol does not sterilize the leech surface and secretions [28]. Although we believe that it may be reasonable to administer a prophylactic antibiotic agent, such as a fluoroquinolone, to patients undergoing leech therapy, it is clear that additional studies are needed to demonstrate the efficacy of this practice. Summary Medicinal leech therapy used in the setting of vascular congestion after reconstructive surgery may be complicated by infection with Aeromonas, a leech endosymbiont. We have reviewed the features of 25 cases of leech-related Aeromonas infection. The severity of such infections can range from mild cellulitis to bacteremia and septic shock. There is a significant risk of flap or replantation loss as well. Recommended treatment includes prompt debridement of affected tissues and administration of antibiotics, generally a third-generation cephalosporin or fluoroquinolone. Prophylaxis for Aeromonas infection during leech use may be prudent, although the impact of prophylactic antibiotics on the risk of infection after leech application is unknown.