4 cases of levaquin induced tendintis (orign spansih)


Mica magazine of Chile
Issn0034-9887 versi printed
Rev. m. Chilev.130n.11Santiagonov.2002
Rev Méd Chile 2002; 130: 1277-1281

Associated aquiliana Tendinitis
to the levofloxacino use:
communication of four cases
Claudius Hoops And, Claudius Flowers W, Sergio Mezzano A.

Levofloxacin associated Achilles
tendinitis. Report of four you marry

Fluoroquinolone-associated tendinitis plows well described in the literature, but these plows not frequently observed and usually plows related to the oldest fluoroquinolones. Levofloxacin is to recently introduced fluoroquinolone. In this to paper we report four you marry (three female, aged 39 to 70 years old) of Achilles tendinitis occurring in a period of few months. Two patients on chronic dialysis, one kidney transplant recipient, and one patient with chronic vasculitis, both with normal renal function. All were chronically using corticosteroids. In the four you marry, bilateral tendinitis had an acute onset with involvement and was invalidating. In 3 you marry the onset of tendinitis was early during levofloxacin treatment and in 1 marries, it began 10 days to after the end of the treatment. All patients were treated with rest and physiotherapy, two were treated with non-steroidal anti-inflammatory drugs. All patients had to completes recovery to alter 3-8 weeks (Rev Méd Chile 2002; 130: 1277-81).


Received the 13 of June, 2002. Accepted the 25 of September, 2002.
Laboratory of Nefrología, Institute and Service of Medicine, Medicine Faculty, Austral University of Chile, Valdivia, Chile.

In the last 15 years there has been a considerable increase in the use of new antibiotics of ample phantom, like the cefalosporinas and fluoroquinolonas (FQ) 1 , 2 .

In recent years new FQ for their commercialization in our country and between these have been approved the levofloxacino, of long average life, with a phantom against gram-negative and gram-positive germs 3 .

The associated tendinitis to FQ are described in Literature, but infrequent and they are related generally to the oldest FQ.

We communicated four cases of appeared aquiliana tendinitis during the treatment with levofloxacino.

Case 1

Patient of masculine sex, 52 years, diabetic type 2, with chronic rejection of renal transplant and renal insufficiency chronic terminal in ambulatory continuous peritoneodiálisis. In treatment with diet, cyclosporin 50 mg/día, azatioprina 50 mg/día, prednisona 10 mg/día, diltiazem 90 mg each 12 h, clonazepam 0.5 mg/día, aspirin 100 mg/día, fólico acid 2 mg/día, calcium carbonate 1,125 mg each 12 h and each 12 20 paroxetina mg h. was hospitalized by an acute neumopatía and treatment with ceftriaxona 1 began g/día IV that received by 24 h, being replaced by 500 levofloxacino good mg/día PO. Presento' evolution and was registered to the fifth day of hospitalization, with indication to continue treatment and ambulatory control. Two days later it appeared bilateral aquilianos sinews, greater pain to left, than it caused important functional impotence to him with great difficulty to ramble. A bilateral aquiliana tendinitis was diagnosed. It was evaluated by traumatólogo, initiating treatment with diclofenaco 50 mg each 12 h PO and fisioterapia. Important pain by 2 weeks persisted, with progressive diminution of this one and complete recovery after 3 weeks.

Case 2

Patient of feminine sex, 39 years, carrier of renal insufficiency chronic secondary terminal to lúpica nefropatía in weekly chronic hemodiálisis, treatment with metilprednisolona 4 mg in alternating days, calcium carbonate 1,125 mg each 12 h, metildopa 125 mg/día, fluoxetina 40 mg/día, alprazolam 0.25 mg at night, clonazepam 0.5 mg/día, eritropoietina 3,000 weekly units and acid 2 fólico mg/día. Being in stable conditions and without lúpica activity, he presented/displayed acute bronchitis, receiving levofloxacino 500 mg/día PO. Six days later appeared great very intense poliartralgias of and small joints, without arthritis, associated to intense pain in both aquilianos sinews. A bilateral aquiliana tendinitis was diagnosed, dealing it with diclofenaco 100 mg/día PO and the levofloxacino was suspended. Nevertheless, the picture got worse arriving at absolute the functional impotence. It continued in treatment with diclofenaco and fisioterapia. The intense pain in both aquilianos sinews persisted by 3 weeks and later it yielded gradually, recovering completely.

Case 3

Patient of feminine sex, 60 years, with antecedents of arterial hypertension and poliquístico kidney of the adult who evolved to the terminal renal insufficiency receiving renal transplant of related alive donor at the age of 47 years. Post evolved transplants in good conditions, with arterial hypertension controlled and stable renal function (creatininemia 1.4 mg/dL), in treatment with each 12 150 cyclosporin mg h, prednisona 7.5 mg/día, 100 azatioprina mg/día, valsartán 80 mg/día, propanolol 40 mg each 12 h and 200 bezafibrato mg/día. In August of 2001 it presented/displayed an acute neumopatía reason why levofloxacino 500 was indicated mg/día PO. After 6 days of treatment initiated acute pain in both aquilianos sinews, with almost absolute functional impotence. Evaluated by traumatólogo, a bilateral aquiliana tendinitis was diagnosed. Treatment with fisioterapia was indicated, did not receive antiinflammatory. It persisted with important pain by a month, after as it diminished progressively until recovering completely after 2 months.

Case 4

Patient of feminine sex, 70 years, with antecedents of arterial hypertension and one recurrent linfocitaria vasculitis, with predominant commitment of cutaneous and polineuropático type of 12 years of evolution, in chronic treatment with prednisona 15 mg/día, enalaprila 5 mg each 12 h, each 12 300 400 carbamazepina mg/día and gabapentín mg h. By an acute rinosinusitis prescribed 500 levofloxacino mg/día that took by 7 days. Ten days after finalized the treatment he initiated in acute form intense pain in both aquilianos sinews that functional impotence caused to him absolute. A bilateral aquiliana tendinitis was diagnosed receiving fisioterápico treatment. They were not prescribed antiinflammatory. It evolved totally with intense pain during several weeks, yielding after 2 months, with complete recovery without sequels.

DISCUSSION

From mid the decade of 1980-89 the use of the FQ has gone in progressive increase. These are antibiotic synthetic that inhibit the bacterial DNA-girasa, necessary for the synthesis of DNA, that have an ample phantom against gram-negative and gram-positive germs and that have demonstrated to be relatively safe 3 .

In the last 10 years the pharmaceutical industry has developed new FQ of long average life, that its administration allows to the day once. Between these levofloxacino 4 stands out , described with a very good profile of tolerance, better than other FQ available in market 5 what, added to the characteristics mentioned previously, it makes an antibiotic very attractive. Nevertheless, along with the increasing number of agents available has appeared the preoccupation about its adverse effects and their true security.

In this article we communicated four cases of severe aquiliana tendinitis, associated to the levofloxacino use, observed in the lapse of few months.

The first published case of tendinitis associated to the FQ use dates from 1983 in a patient with renal insufficiency that received norfloxacino 6 and an incidence approximated for the FQ in general of 15-20 by 100,000 treated patients 7 has been considered , 8 . The series of cases communicated in Literature are little being with the greater number of patients originated ones in France 7 - 14 . Particularly with levofloxacino, although the tendinitis like a possible adverse effect is mentioned, this one seems to be a rare event since in previous clinical studies to the commercialization of the drug an incidence of only 1 case by 3,400 treated patients 5 communicated , 15 , being still more rare the tendínea rupture with an incidence of than 1 by 250,000 patients less treated 16 , 17 .

The first case in the Literature of associated tendinitis to levofloxacino was communicated by Lewis ET to in 1999 15 . This author described a old woman with important deterioration of the renal function that as a result of one neumonía received levofloxacino 500 mg/día by 10 days and that to the third day of initiate the treatment initiated a bilateral aquiliana tendinitis that caused important functional incapacity to him and that it lasted four weeks 15 . Of the cases that we described, all of them appeared with bilateral aquiliana tendinitis, an important functional impotence that it lasted several weeks; both first they had a terminal renal insufficiency in dialysis, the third patient one was one transplanted with normal renal function. The fourth case corresponded to a old woman who also presented/displayed a normal renal function.

Patogenia of these injuries is not well well-known. The tendinopatía can appear suddenly, even after a dose of FQ 8 , which suggests the possibility of a direct toxicity, or after many days of treatment and after to have discontinued drug 18 .

Of the cases that we showed, in the three first it appears to the 6 days of treatment and in the quarter, after 10 days of finalized the antibiotic.

There are few studies of the histológicas injuries. To necrosis with neovascularización, edema interstitial and degenerativas injuries with fissures but without infiltrated inflammatory or vasculitis 19 have been indicated .

Recent studies in vitro and in animals of experimentation have shown that the incubation of fibroblasts of sinew of Aquilles with ciprofloxacino has caused a significant diminution in the cellular proliferation and an stimulation of the activity of degradation of the matrix by fibroblasts 20 . In rats the pefloxacino diminishes the activity of synthesis of proteoglicanos and induces oxidativo damage of the colágeno of type I, with identical alterations to the observed ones in the experimental model of isquemia-reperfusión of sinew 21 .

En una serie de 100 pacientes se observó que el compromiso tendinoso asociado al uso de FQ sería más frecuente en hombres, con una relación aproximada de 3:1. El sitio más frecuentemente comprometido son los tendones aquilianos y muy frecuentemente es bilateral13. De los casos que comunicamos ocurridos con levofloxacino, 3 fueron mujeres y en todos el compromiso fue bilateral.

El uso de corticoides en concomitancia con FQ se ha reconocido como un factor de riesgo para desarrollar tendinopatía. Hasta 41% de los casos publicados se asociaron a corticoides, sea administrados crónicamente o como una única inyección previa al tratamiento con FQ. Los cuatro pacientes que describimos recibían corticoides. También se ha relacionado a la insuficiencia renal crónica, incluyendo pacientes en diálisis8,13,22-28. Esto podría ser debido, al menos en parte, a una excreción renal del fármaco disminuida; sin embargo, la ruptura espontánea de tendones ha sido descrita como una rara, pero clásica complicación de la enfermedad renal y particularmente en pacientes trasplantados que reciben corticoides y con hiperparatiroidismo secundario28-31. El estrés mecánico probablemente también juega un rol. Los tendones que soportan grandes cargas, como el aquiliano, el tendón del cuádriceps y el tendón del manguito de los rotadores se han descrito frecuentemente en la literatura como afectados por tendinopatías asociadas al uso de FQ18. También la edad ha sido considerada un factor de riesgo24, presumiblemente a causa de un clearance disminuido del fármaco.

La historia y el examen físico son claves para el diagnóstico. A los pacientes con síntomas de tendinitis se les debe preguntar por el uso de antibióticos en los 90 días precedentes. La mayor parte de los pacientes presenta síntomas dentro de las dos semanas siguientes al inicio de los antibióticos, sin embargo, este período puede variar de 1 día a 3 meses. Las tendinitis asociadas al uso de FQ difieren de otras tendinitis por el inicio agudo y por el intenso dolor espontáneo o a la palpación, lo que es coincidente con el modo de presentación en nuestros pacientes. Si bien el compromiso bilateral del tendón de Aquiles15,12 ha sido el más frecuentemente comunicado, la tendinitis y ruptura de otros tendones inducida por FQ debe considerarse en todos los pacientes con dolor tendinoso e historia reciente de uso de FQ.

La resonancia nuclear magnética (RNM) puede ser útil en el diagnóstico y manejo de esta complicación. Se han señalado características típicas de cambios intratendíneos. Sería un método preciso para identificar y clasificar la tendinitis y detectar el riesgo de ruptura32.

La ecografía es útil para mostrar anormalidades de los tendones, tales como ruptura y edema alrededor del tendón7,8,25.

El tratamiento consiste en la suspensión inmediata de la FQ y el reposo del tendón afectado. Si se considera que la tendinitis es leve y el paciente es confiable, podría bastar la recomendación de reposo del miembro afectado por 2 a 6 semanas. Si se sospecha ruptura tendínea o la RNM muestra su riesgo potencial, el paciente requerirá un manejo especializado por el traumatólogo.

Aun con un diagnóstico y manejo precoz la tendinitis cura lentamente. La ruptura del tendón puede ocurrir en un número significativo de casos a pesar de un cuidado apropiado. El tiempo de recuperación es muy variable, pero se ha comunicado un promedio que va de 3 semanas para la tendinitis hasta 3 meses o más para una ruptura tendínea. Si no hay una ruptura completa, se puede esperar una recuperación total, en caso contrario la incapacidad puede ser permanente. Los pacientes no deben recibir tratamiento con ninguna FQ por una segunda vez.

En conclusión, las FQ se han descrito como fármacos en general seguros, efectivos y con un muy buen perfil de tolerancia. La tendinitis y la ruptura tendínea son efectos adversos raros causados por las FQ más antiguas. Con la aparición de FQ de una dosis diaria, los médicos probablemente usarán cada vez más frecuentemente estos fármacos. Sin embargo, no hay información disponible si con el uso extendido de las FQ de introducción más reciente estas reacciones adversas se verán con mayor frecuencia que con las antiguas FQ. Según nuestro conocimiento, hay muy pocos casos comunicados en la literatura acerca de esta complicación con las nuevas FQ y especialmente con el levofloxacino15,33.

Estos antibióticos deberían ser evitados, si es posible, en pacientes con enfermedad renal, ancianos y en quienes reciben corticoides.

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_______________

Correspondencia a: Dr. Sergio Mezzano A. Laboratorio de Nefrología, Universidad Austral de Chile. Hospital Clínico Regional Valdivia. Simpson 850, Valdivia, Chile. Fono-Fax: 56 63 215890. E-mail: smezzano@uach.cl


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