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Saudi Journal of Kidney Diseases and Transplantation
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Table of Contents   
CASE REPORT  
Year : 2018  |  Volume : 29  |  Issue : 5  |  Page : 1207-1210
Lymphocutaneous nocardiosis in a kidney transplant patient successfully treated with tigecycline


1 5th Department of Medicine, Division of Infectious Diseases, Evangelismos Hospital, Athens, Greece
2 Department of Nephrology, Evangelismos Hospital, Athens, Greece
3 Department of Microbiology, Evangelismos Hospital, Athens, Greece

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Date of Submission05-Sep-2017
Date of Decision10-Oct-2017
Date of Acceptance22-Oct-2017
Date of Web Publication26-Oct-2018
 

   Abstract 

Cutaneous nocardiosis is an infrequent infection which has been increasingly reported in immunocompromised patients. Although trimethoprim-sulfamethoxazole is considered to be the agent of choice for treatment of nocardiosis, newer antimicrobials such as tigecycline have been proven to be effective in vitro, as well. We report the first case of primary cutaneous nocardiosis in a renal transplant recipient having corresponded well to treatment with tigecycline.

How to cite this article:
Mylona E, Papastamopoulos V, Giannopoulou M, Perivolioti E, Psaroudaki Z, Skoutelis A. Lymphocutaneous nocardiosis in a kidney transplant patient successfully treated with tigecycline. Saudi J Kidney Dis Transpl 2018;29:1207-10

How to cite this URL:
Mylona E, Papastamopoulos V, Giannopoulou M, Perivolioti E, Psaroudaki Z, Skoutelis A. Lymphocutaneous nocardiosis in a kidney transplant patient successfully treated with tigecycline. Saudi J Kidney Dis Transpl [serial online] 2018 [cited 2018 Nov 15];29:1207-10. Available from: http://www.sjkdt.org/text.asp?2018/29/5/1207/243954

   Introduction Top


The wide use of newer immunosuppressive drugs has revolutionized organ transplantation while increasing the incidence of opportunistic infections. Nocardia spp. are soil-borne, aerobic bacteria, distributed worldwide as saprophytes. Infection is caused by inhalation or through the skin by accidental inoculation.[1] Cutaneous nocardiosis is an infrequent infection which has been increasingly reported in immuno-compromised patients, although immunocompetent individuals may also be affected.[2] Trimethoprim-sulfomethoxazole (TMP/SMX) is considered to be the treatment of choice for nocardiosis.

Although new antimicrobials such as tigecycline have been shown to be effective in vitro,[3],[4],[5] there is practically no clinical experience with these drugs.

To the best of our knowledge, this is the first reported case of primary cutaneous nocardiosis in a renal transplant recipient having corresponded well to treatment with tigecycline.


   Case Report Top


A 64-year old Caucasian man was admitted to our department for evaluation of low-grade fever and subcutaneous nodules in his right upper extremity. His medical history was significant for renal transplantation in 2001, due to chronic kidney disease resulted from vesicoureteral reflux as well as coronary artery disease, with percutaneous coronary intervention in 2005. He had experienced two episodes of rejection, but no CMV infection and his maintenance immunosuppression included everolimus (1.5 g/day), mycophenolic acid (750 mg/day) and prednisolone (2.5 mg/day). The rest of his medication included carvedilol (6.25 mg/day), furosemide (20 mg/day), moxonidine (0.6 mg/day) eplerenone (50 mg/day), ezetimibe 10/40, and allopurinol (150 mg/ day). He did not receive TMP/SMX as prophylaxis.

In April 2017 (16 years after his transplantation), one week before admittance, the patient presented to his general practitioner (GP) with a painful nodule at the dorsal surface of his right 5th finger, a few days after gardening with bare hands. The GP prescribed cipro-floxacin and clindamycin. While on this treatment, the initial abscess drained pus and several new painful, red nodules appeared along the lymphatic drainage path on the anterior surface of the ipsilateral forearm. The patient visited again the GP who incised the abscess on the 5th finger. Moreover, he suggested continuation of the aforementioned medication and admission at the hospital.

On admission, the patient denied symptoms from the respiratory or other systems. On physical examination, he was afebrile, without any remarkable clinical finding except for a tender ulcer 2 cm × 2 cm on the posterior surface of his right 5th finger, which was edematous, being surrounded by a smaller nodule [Figure 1]a, as well as 4–5 tender and fluctuated nodules on the ipsilateral forearm which was not edematous or erythematous [Figure 1]b. There was no axillary lymphadenopathy or hepatosplenomegaly.
Figure 1: The ulcer on the posterior surface of the 5th finger, having already drained pus and been incised (a), as well as the red nodules along the lymphatic drainage path on the ipsilateral forearm (b). The initial abscess (c) and the nodules on the forearm (d) after 10 days of tigecycline iv.

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Laboratory findings were as follows: Hemoglobulin – 13 mg/dL, white cell count – 9.950/ mm3, platelets – 245.000/mm3, urea, 89 mg/dL, creatine, 2.88 mg/dL, erythrocyte sedimentation rate 97 mm/L, C-reactive protein, 9.97 mg/dL (normal <0.5). Liver function and routine chest radiograph were normal.

Urine, blood and skin cultures, a skin biopsy and aspiration of two nodules were performed. Blood and urine cultures were negative. Gram and the Ziel–Nielsen stains of the aspirate were also negative. While waiting for the skin and aspirate culture results, the patient received empirically i.v. tigecycline and despite the lack of clinical indications, he was subjected to computed tomography scan of the lungs and the brain which were normal. On day 10 of hospitalization cultures grew branching Gram-positive bacteria, identified as Nocardia asteroides. The organism was susceptible to amikacin (≤1 μg/mL), imipenem (<1.5 μg/mL), (TMP/SMX) (≤0.5 Mg/mL), linezolid (≤0.5 μg/mL), and tigecycline (≤0.125 Mg/mL). The cutaneous lesions were already significantly improved [Figure 1]c and [Figure 1]d after 14 days with tigecycline, which had been well tolerated by the patient (he suffered no nausea or vomiting, no abnormality in the liver or pancreatic function tests or prolongation of the activated partial thromboplastin time). The patient discharged from the hospital on TMP/SMX (960 mg × 2/day) for six months. The treatment resulted in full recovery, with no relapse on follow-up.


   Discussion Top


Cutaneous nocardiosis may represent either primary cutaneous infection or disseminated infection with skin involvement. There are two acute forms of the primary cutaneous disease, the superficial skin infection and the lymphocutaneous infection or nodular lymphangitis.[2] The latter is characterized by inflammatory nodules along the lymphatics draining a primary skin infection, which was the clinical presentation of the present patient.

Primary cutaneous infection is usually caused by N. braziliensis (less commonly N. asteroides) and generally occurs in immunocompetent hosts following a local trauma. In immunocompromised patients, the infection is usually disseminated and N. asteroides is the species most commonly identified.[6],[7] Our patient, although immunocompromised, suffered from primary cutaneous infection, caused by N. asteroides.

Most cases of nodular lymphangitis result from infections with five microbial pathogens: sporothrix scheckii, atypical mycobacteria, N. braziliensis, Francisella tularensis, and leishmania.[8] Common bacteria such as group A streptococci or Staphylococci aureus may be included in the differential[8] but the fact that our patient had already received clindamycin without response, made these bacteria as cause of the primary disease, a remote possibility. However, the patient was immunocompromised and although, the clinical presentation of his disease was subacute and indolent permitting us to wait for the cultures’ results, the fact that he had been subjected to surgical interventions, made secondary infection by common bacteria possible, leading us to initiate tigecycline.

Nocardia requires a minimum of 72 h to become evident in the culture, but colonies may take up to 14 days to appear, as in the present case, offering us the opportunity to realize that Nocardia nodular lymphangitis corresponded well to treatment with tigecycline.

TMP/SMX has conventionally been the agent of choice for the treatment of nocardiosis.[7] Minocycline has been used for patients who are intolerant to sulfonamides. Combination therapy with imipenem or a third-generation cephalosporin and amikacin is usually recommended for severely immunocompromised patients or for those with central nervous system involvement, disseminated or advanced disease. New antimicrobials such as tigecycline have demonstrated adequate in vitro activity,[3],[4],[5] but their effectiveness in vivo is actually unknown. More specifically, in the literature, the in vitro activities of newer and more traditional antibiotics have been compared against clinical isolates of more than 10 different Nocardia species such as N. cryiacigeorgica, N. farcinica, N. otitidiscaviartum, N. abscessus, N. beijingensis, N. nova, N. veterana, N. transvalensis, N. carnea and N. breazilensis.[4] TMP/SMX continues to have an excellent activity in general, as well as minocycline. However, some strains of N. farcinica, N. veterana, and N. beijingensis were inhibited by minocycline at 2 mg/L, which falls in the intermediate susceptibility category. Amikacin was uniformly active against all isolates but N. transvalensis. As far as carbapenems are concerned, N. farcinica and N. otitidiscaviarum were often resistant to penems, whereas N. transvalensis seems to be intrinsically resistant to them. Moxifloxacin was reported active against the majority of the isolates but its variable activity, against N. beijingesis in particular, makes it necessary to perform susceptibility studies before its use. Tigecycline was active against the majority of isolates, even against imipenem-resistant or TMP/SMX-resistant isolates. Linezolid presented the lowest MICs of all antimicrobials evaluated.[4]

To the best of our knowledge, this is the first report of primary subcutaneous nocardiosis having been successfully treated by tigecycline. The inclusion of Nocardia in the spectrum of tigecycline would permit its use in the treatment of complicated wound infections in immunocompromised patients under some circumstances (for example an injury) where it would be convenient to treat a possible nocardial together with common bacterial infection.

Conflict of interest: None declared.

 
   References Top

1.
Saubolle MA, Sussland D. Nocardiosis: Review of clinical and laboratory experience. J Clin Microbiol 2003;41:4497-501.  Back to cited text no. 1
    
2.
Kalb RE, Kaplan MH, Grossman ME. Cutaneous nocardiosis. Case reports and review. J Am Acad Dermatol 1985;13:125-33.  Back to cited text no. 2
    
3.
Lai CC, Liu WL, Ko WC, et al. Multicenter study in Taiwan of the in vitro activities of nemonoxacin, tigecycline, doripenem, and other antimicrobial agents against clinical isolates of various Nocardia species. Antimicrob Agents Chemother 2011;55:2084-91.  Back to cited text no. 3
    
4.
Cercenado E, Marín M, Sánchez-Martínez M, et al. In vitro activities of tigecycline and eight other antimicrobials against different Nocardia species identified by molecular methods. Antimicrob Agents Chemother 2007;51:1102-4.  Back to cited text no. 4
    
5.
Maraki S, Scoulica E, Nioti E, Tselentis Y. Nocardial infection in Crete, Greece: Review of fifteen cases from 2003 to 2007. Scand J Infect Dis 2009;41:122-7.  Back to cited text no. 5
    
6.
Lerner PI. Nocardiosis. Clin Infect Dis 1996;22:891-903.  Back to cited text no. 6
    
7.
Brown-Elliott BA, Brown JM, Conville PS, Wallace RJ Jr. Clinical and laboratory features of the Nocardia spp. Based on current molecular taxonomy. Clin Microbiol Rev 2006;19: 259-82.  Back to cited text no. 7
    
8.
DiNubile MJ. Nodular lymphangitis: A distinctive clinical entity with finite etiologies. Curr Infect Dis Rep 2008;10:404-10.  Back to cited text no. 8
    

Top
Correspondence Address:
Dr. Eleni Mylona
5th Department of Medicine, Division of Infectious Diseases, Evangelismos Hospital, Athens
Greece
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DOI: 10.4103/1319-2442.243954

PMID: 30381521

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