SCIENTIFIC ARTICLE

Ciprofloxacin-Resistant Aeromonas Infection Following Leech Therapy for Digit Replantation: Report of 2 Cases Nickolas A. van Alphen, MD, Alexandra Gonzalez, MS, Maureen C. McKenna, MD, Theresa K. McKenna, MD, Brian T. Carlsen, MD, Steven L. Moran, MD Medicinal leeches are commonly used after finger replantation to treat surgically unsalvageable venous congestion. Infection from Aeromonas hydrophila is a recognized complication of leech therapy that can be underestimated by the medical community. Ciprofloxacin and trimethoprim-sulfamethoxazole are the most commonly recommended prophylactic antibiotics used to prevent A. hydrophila infections during leech therapy. Here, we report 2 cases of ciprofloxacin-resistant Aeromonas infections, occurring within 4 months of each other. Both cases developed after leech therapy for unsuccessful digital replantation. These infections were successfully treated with ceftriaxone. Ciprofloxacin-resistant Aeromonas should be recognized when determining prophylactic antibiotic protocols for replant centers when leech therapy is used for finger replantation. (J Hand Surg Am. 2014;39(3):499e502. Copyright Ó 2014 by the American Society for Surgery of the Hand. All rights reserved.) Key words Replantation, leeches, antibiotic resistance, antibiotic prophylaxis, Aeromonas.

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effectively used in the salvage of venous congested tissue after digit replantation surgery.1 The most noteworthy risk of leech therapy is infection in the treated part, usually involving Aeromonas hydrophila.2,3 Reported incidences of infection range from 2% to 36% of cases.4 Aeromonas species, including A. hydrophila, live in the gut of the leech, where they play a symbiotic role in the digestion of blood.3 Complications due to A. hydrophila infection can range from minor wound EDICINAL LEECH THERAPY HAS BEEN

From the Department of Surgery, Division of Plastic & Reconstructive Surgery, Mayo Clinic, Rochester, Minnesota. Received for publication July 30, 2013; accepted in revised form November 26, 2013. We would like to acknowledge the diligent work of Division of Infectious Disease at Mayo Clinic for their help in identifying the resistant organisms presented within this paper. No benefits in any form have been received or will be received related directly or indirectly to the subject of this article. Corresponding author: Steven L. Moran, MD, Division of Plastic Surgery, Mayo Clinic, Mayo Building, 12th floor, 200 First St. SW, Rochester, MN 55905; e-mail: moran.steven@ mayo.edu. 0363-5023/14/3903-0015$36.00/0 http://dx.doi.org/10.1016/j.jhsa.2013.11.041

infection to major cellulitis, abscess, tissue loss, and sepsis.3,5,6 The most common Aeromonas species found in leeches produce similar clinical symptoms and have similar antibiotic sensitivities.7 A major infection can reduce the rates of flap or replant salvage with leech therapy from 80% to 30% or less.2 The use of prophylactic antibiotics is recommended in patients receiving leech therapy because it may decrease the risk of Aeromonas infection.3,4,8 Increasing levels of multidrug resistance have been reported in Aeromonas.4 Despite this, resistance to the most commonly recommended prophylactic antibiotics, fluoroquinolone and trimethoprimsulfamethoxazole (TMP-SMX), has been reported to be low.4,9 Within 4 months, we encountered 2 cases of ciprofloxacin-resistant Aeromonas infections after digit replantation surgery arising from commercially available leeches. Here, we review these 2 cases and provide treatment recommendation for antibiotic prophylaxis when using leeches. CASE 1 A 50-year-old man was transferred to our facility after a table saw amputation of 4 fingers through the

Ó 2014 ASSH

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Published by Elsevier, Inc. All rights reserved.

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proximal phalanges. The patient had a past medical history relevant for tobacco dependency, polysubstance abuse including methamphetamine, and a previous methicillin-resistant Staphylococcus aureus skin and soft tissue infection not involving the upper extremity. The index, long, and ring fingers were successfully replanted. Only 1 vein could be repaired per finger. Perfusion and venous drainage were initially satisfactory; however, 48 hours after replantation, the patient was started on leech therapy and systemic anticoagulation for venous congestion. Ertapenem was administered for prophylaxis against the possibility of recurrent methicillin-resistant S. aureus during the leech therapy based on the infectious disease consultant’s recommendation. On postoperative day 9, the index finger developed signs of poor inflow with sluggish capillary refill, and the index finger was removed. The middle and ring fingers were amputated 22 days postreplantation. The amputation sites were covered with a reverse-radial forearm flap. This procedure was complicated by a wound infection resulting in marginal flap necrosis. The wound was cultured and grew Aeromonas species resistant to ertapenem, fluoroquinolone, and ampicillin/sulbactam (Table 1). He was started on vancomycin (2,300 mg intravenously [IV] q12h) and piperacillin/tazobactam (3.4 g IV q6h) empirically. Based on susceptibilities, his antibiotic regimen was changed to ceftriaxone (2 g IV q24h) and TMP-SMX double-strength (2 tablets q12h). Double coverage was provided to cover any problems in the consistent administration of home intravenous ceftriaxone antibiotic therapy. One month after starting treatment with ceftriaxone and TMP-SMX, the surgical wound was well healed with no signs of infection.

seen at an outside facility for wound drainage and foul odor coming from the long finger amputation site. Culture swabs grew A. hydrophila that was resistant to TMP-SMX and partially resistance to ciprofloxacin (Table 2). Based on the sensitivity profile, the patient’s antibiotic therapy was changed to cefepime (2 g IV q12h), metronidazole (500 mg by mouth [PO] 3 times daily) and vancomycin (1600 mg IV q12h). The patient was seen back at our institution in 48 hours. At this time, swab cultures taken at our institution grew Proteus vulgari, which was resistant to ciprofloxacin; Morganella morganii, which was resistant to ciprofloxacin; and A. hydrophila. Both Proteus and Morganella species were TMP-SMX resistant; however, they were found to be ceftriaxone susceptible, similar to the A. hydrophila. Antibiotic regimen was changed to a 14-day course of ceftriaxone (2 g IV daily). The wound then healed without complication, and there have been no signs of recurrent infection.

CASE 2 A 35-year-old man amputated his left index and long fingers through the proximal interphalangeal joints on a table saw. He initially underwent closure of the index amputation site and ectopic replantation of the index finger in the long finger position. Two veins were repaired. The next day, leech therapy was started on the nail bed area for venous congestion. The patient was receiving ciprofloxacin (500 mg orally twice daily) as prophylaxis for Aeromonas. Leech therapy was continued for 7 days. On postoperative day 8, replantation failure was confirmed, and the replanted finger was removed. Four days after being discharged, the patient was

MICROBIOLOGICAL EVALUATION OF LEECHES Following these 2 cases, our Microbiology Department conducted an investigation to determine the source of the antibiotic resistance. They processed cultures from 4 unused leech specimens from our leech tank. The leeches had been purchased commercially from multiple sources and then stored in the tank. Two of the leeches were ground and cultured to media. Using matrix-assisted laser desorption/ionization spectrometry, microorganisms recovered were identified as Aeromonas species with similar sensitivity profiles, including susceptibility to ciprofloxacin and TMP-SMX. Aeromonas veronii, which has a similar clinical presentation to A. hydrophila,4 was also growing in one of the specimens. Gut tissue was

J Hand Surg Am.

TABLE 1. Antibiotic Sensitivity and Resistance Profile of Aeromonas in Case 1 Sensitive

Resistant

Tobramycin

Ciprofloxacin

Ceftriaxone

Ertapenem

Amikacin

Ampicillin-sulbactam

Meropenem

Levofloxacin

Ceftaridime Piperacillin-tazobactam TMP-SMX Cefepime Gentamicin

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and TMP-SMX resistant A. hydrophila infection after leech therapy.5,6,9 Contrary to our study, Wang et al9 found the culture swabs of their leech aquarium grew multiple Aeromonas species that were all susceptible to the tested antibiotics including ciprofloxacin and TMP-SMX; however, unlike our report, they were not able to test cultures from leeches’ gastrointestinal tract. They concluded that the resistant strain might have been isolated to the particular leech used on their patient.9 In our investigation, ciprofloxacin resistance was only found in samples from the gastrointestinal tract. More recently, Giltner et al6 reported a case of ciprofloxacin-resistant A. hydrophila infection after leech therapy of a free flap for mandibular reconstruction. Consistent with our findings of Aeromonas isolated from tank water, Giltner et al6 did not find any resistant Aeromonas in the water or on the tank surface but did find resistant Aeromonas during midgut dissection and culturing of the leeches. The potential risk for infections associated with leech therapy should not be underestimated. Both of our patients experienced digital loss in addition to subsequent local tissue damage, rehospitalization, and the need for additional antibiotics. After evaluating the sensitivity profiles of the leeches in our institution and the profiles of the infections in our patients, it became apparent that medicinal leeches may harbor Aeromonas species resistant to previously accepted prophylaxis treatments such as ciprofloxacin and TMP-SMX. When determining the correct antibiotic prophylaxis during leech therapy, the possibility of encountering a ciprofloxacin-resistant strain should be evaluated. We recommend considering ceftriaxone as a first-line choice for prophylactic treatment during leech therapy. Based on the literature, third-generation cephalosporins appear to be consistently effective against Aeromonas species.3,8,14 Both of our patients had successful recoveries after treatment with ceftriaxone. Cost differences between antibiotics can differ from institution to institution; however, the daily cost of ciprofloxacin is $0.25 orally and $6 intravenously, compared with cefdinir (the oral form of ceftriaxone), which is $2 orally and $1 intravenously. Thus, the cost of the antibiotic alone will likely have a negligible effect on the overall cost of treatment. There is a need to reevaluate standards of antibiotic prophylaxis. We encourage other institutions to test antibiotic susceptibilities of their local leeches in order to select appropriate antibiotic prophylaxis and prevent further development of drug resistance.

TABLE 2. Sensitivity and Resistance Profile of Aeromonas in Case 2 Sensitive

Moderately Sensitive

Resistant

Ceftazidime

Ciprofloxacin

Ampicillin

Ceftriaxone

Nitrofurantoin

Ampicillinsulbactam

Cefepime

Levofloxacin

Cefazolin

Imipenem

TMP-SMX

Tobramycin Gentamicin

obtained from 2 other leeches, one through needle aspiration and the other through gut dissection. Both of these specimens grew A. hydrophila and A. veronii resistant to ciprofloxacin but sensitive to TMP-SMX and ceftriaxone. The water received with the leeches was also cultured, but no growth of Aeromonas species was detected. DISCUSSION Infections secondary to leech therapy are rare when using appropriate antibiotic prophylaxis.2,3 Thirdgeneration cephalosporins, TMP-SMX, and fluoroquinolones have been consistently reported to be effective as prophylaxis, with few reports of resistance in Aeromonas species.10,11 Ciprofloxacin is the current recommendation because it has favorable resistance profile and good oral availability.4 Chepeha et al10 also reported complete success of tissue survival without infection after ciprofloxacin or ciprofloxacin/TMP-SMX for leech therapy. Although fluoroquinolones currently show the broadest coverage against Aeromonas infection, the patients we presented grew a ciprofloxacin-resistant Aeromonas species. Other gram-negative rods have been cultured from leeches, but most isolated organisms have been sensitive to the same agents that are active against Aeromonas species.11 The swab cultures of the patient in our second case were growing P. vulgaris and M. morganii with similar sensitivity profiles to the A. hydrophila previously cultured from our second patient. These bacteria have been previously identified as part of the leech microflora.12,13 All these microorganisms had resistance or were more resistant to the most commonly recommended prophylactic antibiotics, ciprofloxacin and TMP-SMX. Aeromonas resistance to ciprofloxacin is rare, but recently several cases were reported of ciprofloxacin J Hand Surg Am.

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REFERENCES

8. Lineaweaver WC, Furnas H, Follansbee S, et al. Postprandial Aeromonas hydrophila cultures and antibiotic levels of enteric aspirates from medicinal leeches applied to patients receiving antibiotics. Ann Plast Surg. 1992;29(3):245e249. 9. Wang EW, Warren DK, Ferris VM, Casabar E, Nussenbaum B. Leech-transmitted ciprofloxacin-resistant Aeromonas hydrophila. Arch Otolaryngol Head Neck Surg. 2011;137(2):190e193. 10. Chepeha DB, Nussenbaum B, Bradford CR, Teknos TN. Leech therapy for patients with surgically unsalvageable venous obstruction after revascularized free tissue transfer. Arch Otolaryngol Head Neck Surg. 2002;128(8):960e965. 11. Haycox CL, Odland PB, Coltrera MD, Raugi GJ. Indications and complications of medicinal leech therapy. J Am Acad Dermatol. 1995;33(6):1053e1055. 12. Eroglu C, Hokelek M, Guneren E, Esen S, Pekbay A, Uysal OA. Bacterial flora of Hirudo medicinalis and their antibiotic sensitivities in the middle Black Sea region. Ann Plast Surg. 2001;47(1): 70e73. 13. Worthen PL, Gode CJ, Graf J. Culture-independent characterization of the digestive-tract microbia of the medicinal leech reveals a tripartite symbiosis. Appl Environ Microbiol. 2006;72(7): 4775e4781. 14. Braga A, Lineaweaver WC, Whitney TM, Follansbee S, Buncke HJ. Sensitivities of Aeromonas hydrophila cultured from medicinal leeches to oral antibiotics. J Reconstr Microsurg. 1990;6(2): 135e137.

1. Brody GA, Maloney WJ, Hentz VR. Digit replantation applying the leech Hirudo medicinalis. Clin Orthop Relat Res. 1989;245: 133e137. 2. de Chalain TM. Exploring the use of the medicinal leech: a clinical risk-benefit analysis. J Reconstr Microsurg. 1996;12(3): 165e172. 3. Lineaweaver WC, Hill MK, Buncke GM, et al. Aeromonas hydrophila infections following use of medicinal leeches in replantation and flap surgery. Ann Plast Surg. 1992;29(3):238e244. 4. Whitaker IS, Kamya C, Azzopardi EA, Graf J, Kon M, Lineaweaver WC. Preventing infective complications following leech therapy: is practice keeping pace with current research? Microsurgery. 2009;29(8):619e625. 5. Patel KM, Svestka M, Sinkin J, Ruff PIV. Ciprofloxacin-resistant Aeromonas hydrophila infection following leech therapy: a case report and review of the literature. J Plast Reconstr Aesthet Surg. 2013;66(1):e20ee22. 6. Giltner CL, Bobenchik AM, Uslan DZ, Deville JG, Humphries RM. Ciprofloxacin-resistant Aeromonas hydrophila cellulitis following leech therapy. J. Clin. Microbiol. 2013;51(4): 1324e1326. 7. Mackay DR, Manders EK, Saggers GC, Banducci DR, Prinsloo J, Klugman K. Aeromonas species isolated from medicinal leeches. Ann Plast Surg. 1999;42(3):275e279.

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Ciprofloxacin-resistant Aeromonas infection following leech therapy for digit replantation: report of 2 cases.

Medicinal leeches are commonly used after finger replantation to treat surgically unsalvageable venous congestion. Infection from Aeromonas hydrophila...
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