Treatment of Streptococcal Endocarditis with a Single Daily Dose of Ceftriaxone and Netilmicin for 14 Days: A Prospective Multicenter Study

Abstract

A 2-week course of ceftriaxone (2 g) plus netilmicin (4 mglkg), administered as one short daily iv infusion, was evaluated for the treatment of streptococcal endocarditis in an open multicenter study. Of the 52 patients, 31 were infected with viridans streptococci, 18 with Streptococcus bovis, two with Gemella morbillorum, and one with group C Streptococcus; 48 patients were assessable.Infection was cured in 42 cases, 35 treated medically and seven treated both medically and surgically. Five patients died without evidence of active infection, and one relapsed. The bacteriologic failure was due to a strain of G. morbillorum against which no synergy of ceftriaxone and netilmicin was evident in vitro. The serum creatinine level increased during treatment in four cases, all involving patients >65 years old who had renal risk factors; in two of these cases, values did not return to baseline during follow-up. Of 40 patients assessed for auditory function, only one developed decreased perception of borderline significance. Other adverse reactions were mild. This regimen was efficacious, safe, and cost-effective for the treatment of streptococcal endocarditis. However, it must be used with caution for patients with preexisting renal impairment or concomitant exposure to other potentially nephrotoxic agents.Four weeks of treatment with iv penicillin alone or 2 weeks oftreatment with iv penicillin plus an aminoglycoside are effective for streptococcal endocarditis [1,2]. However, such regimens require several daily injections, and the use of aminoglycosides carries a risk of renal toxicity and ototoxicity [2,3]. Two recent developments may allow more convenient and safer treatment ofthis condition. First, a single daily dose of ceftriaxone (a cephalosporin with a prolonged serum half-life) given for 4 weeks has been found to be effective against streptococcal endocarditis [4,5]. This regimen has been used successfully on an outpatient basis and without a permanent iv catheter. Second, recent experimental and clinical evidence has suggested that administration of the total daily dose of an aminoglycoside in a single injection is as effective as administration of the same amount of drug in two or three injections and causes equal or less toxicity [6][7][8][9]. Indeed, in the treatment of experimental streptococcal endocarditis, when given in a single daily dose rather than as multiple doses, aminoglycosides were just as synergistic with ,B-Iactam agents such as penicillin and ceftriaxone [10-13].The purpose of the multicenter study reported herein was to test prospectively the efficacy and safety of a 2-week course of therapy for streptococcal (nonenterococcal) endocarditis with a regimen consisting of ceftriaxone plus netilmicin given once a day. The study was noncomparative since streptococcal endocarditis is a rare disease and the outcome of treatment with penicillin is well known. The efficacy of penicillin is so high that it would have been impossible to recruit enough patients to exclude a type II error. Patients and ...

Infective Endocarditis

“…61,62 Studies performed in Europe, South America, and the United States demonstrated that the combination of once-daily ceftriaxone with either netilmicin or gentamicin administered once daily was equivalent in efficacy to 2 weeks of therapy with penicillin together with an aminoglycoside administered in daily divided doses. 62,63 The 2-week regimen of penicillin or ceftriaxone combined with single daily-dose gentamicin is appropriate for uncomplicated cases of endocarditis caused by highly penicillin-susceptible viridans group streptococci or S bovis in patients at low risk for adverse events caused by gentamicin therapy (Table 4). This 2-week regimen is not recommended for patients with known extracardiac infection or those with a creatinine clearance of Ͻ20 mL/min.…”

2015 ESC Guidelines for the management of infective endocarditis

“…Oczekiwany współczynnik wyleczeń powinien wynosić ponad 95%. W niepowikłanych przypadkach, trzeba zastosować krótki 2-tygodniowy schemat leczenia skojarzonego za pomocą benzylopenicyliny lub ceftriaksonu oraz gentamicyny lub netylmicyny [137,138]. Gentamicynę i netylmicynę należy podawać raz dziennie u pacjentów z prawidłową funkcją nerek oraz IZW wywołanym przez wrażliwe paciorkowce.…”

“…Gentamicynę i netylmicynę należy podawać raz dziennie u pacjentów z prawidłową funkcją nerek oraz IZW wywołanym przez wrażliwe paciorkowce. Ceftriakson w monoterapii lub w połączeniu z gentamicyną lub netylmicyną szczególnie poleca się w przypadku leczenia ambulatoryjnego [137][138][139]. Jeśli nie można przeprowadzić odczulania, pacjenci uczuleni na b-laktamy powinni otrzymywać wankomycynę.…”

INFECTIVE ENDOCARDITIS: TREATMENT AND PREVENTIVE MAINTENANCE (part III)

“…Имеются данные о высокой эффективности 2-недель-ного комбинированного лечения пенициллином и гентами-цином либо цефтриаксоном и нетилмицином [4]. Однако применение указанных курсов лечения оправдано только у больных моложе 65 лет с ИЭ, вызванным высокочувстви-тельными к пенициллину стрептококковыми штаммами (Str.…”

“…Это обусловливает более про-должительное действие на возбудителей высоких концент-раций препарата и увеличение времени постантибиотиче-ского эффекта, до 5-7 ч и более, в то время как при дробном введении этот эффект держится лишь 1-2 ч [5]. В середине 1990-х годов было выполнено 2 проспективных несравни-тельных клинических исследования, в ходе которых сооб-щалось об успешном однократном применении гентамици-на и нетилмицина в сочетании с бета-лактамами при стреп-тококковом ИЭ [4,6]. В это же время в рамках нашего ис-следования была констатирована высокая эффективность и хорошая переносимость однократного применения гента-мицина в дозе 160-320 мг/сут (3 больных) и амикацина в дозе 1000 мг/сут (11 больных), назначавшихся в комбина-ции с бета-лактамными антибиотиками.…”