임균 감염 치료 요법 변경 [Update to CDC’s Treatment Guidelines for Gonococcal Infection, 2020]

미국 질병관리본부는 체중 150 kg 미만인 경우는 세프트리악손 500 mg, 150 kg 이상인 경우는 세프트리악손 1 g을 단회, 근육 주사하는 것을 선호하는 요법으로 가이드라인을 개정하였습니다.

** 이전에는 125-250 mg 세프트리악손에 아지스로마이신 1 g을 일상적으로 병합하는 것을 권고하였습니다. 이 부분은 의대생 때부터 배워 왔던 내용인데 2020.12월 CDC는 이전 권고사항을 변경하였습니다.

변경된 변경 사항에 대한 pdf 파일입니다.

mm6950a6.pdf

0.14MB

이전 권고 사항은 더 낮은 용량의 세프트리악손 plus 아지스로마이신의 병합치료였습니다. 그러나 병합치료에 대한 이전 선호는 이론적 이득에 근거한 것이었고 이제 임균에 대한 아지스로마이신 감수성은 감소되고 있습니다. 더 높은 용량의 세프트리악손이 권고되는데 그 이유는 유병률이 증가되고 있는, 세프트리악손에 더 높은 MIC를 갖는 임균에 대해 낮은 용량의 세프트리악손이 효과가 없을 것 같다는 우려 때문입니다. 클라미디아 동반감염이 배제되지 않았다면 독시사이클린으로 클라미디아를 추정 치료하는 것이 필요합니다.

Preferred regimen ​ "High" dose intramuscular ceftriaxone — Single-agent therapy with ceftriaxone is the preferred regimen for treatment of gonococcal infections. We agree with the following dose recommendations from the United States Centers for Disease Control and Prevention (CDC) for treatment of uncomplicated gonococcal infections: ​ ●For individuals who weigh <150 kg – Ceftriaxone 500 mg intramuscular (IM) in a single dose ●For individuals who weigh ≥150 kg – Ceftriaxone 1 g IM in a single dose ​ These doses of ceftriaxone are higher than previously recommended due to concerns regarding rising gonococcal minimum inhibitory concentrations (MICs) worldwide. High doses of ceftriaxone are also recommended by other national guidelines; for example, 1 g as a single IM dose is recommended by the British Association for Sexual Health and HIV (BASHH) in the United Kingdom, and 1 g (given intravenously) is recommended in Japan. ​ Additionally, routine use of a second agent for treatment of gonococcal infections, which was included in previous CDC treatment guidelines, is no longer recommended. However, if chlamydial coinfection has not been excluded (eg, nucleic acid amplification testing [NAAT] at exposed sites has not been performed), presumptive treatment of chlamydia should be administered at the same time. ​ Ceftriaxone is highly effective against susceptible N. gonorrhoeae. Earlier studies had suggested that ceftriaxone dosed IM at either 125 mg or 250 mg resulted in microbiologic cure in 99 percent of uncomplicated urogenital and anorectal infections. Ceftriaxone is also more effective than oral cephalosporins. In a meta-analysis of trials evaluating treatment of uncomplicated gonorrhea, higher cure rates were reported with ceftriaxone 250 mg than cefixime 400 mg (odds ratio [OR] 1.77, 95% CI 1.11-2.8) with equivalent side effects. However, these doses (125 mg to 250 mg) are unlikely to be effective against isolates with higher MICs, which have increased in prevalence since those trials were performed. Pharmacokinetic and pharmacodynamic modeling and animal studies have demonstrated that a dose of at least 5 mg/kg of ceftriaxone is necessary to achieve levels higher than an MIC ≥0.125 mcg/mL (the threshold for decreased susceptibility to ceftriaxone) for a sufficient duration of time above the MIC. Thus, the CDC has increased the recommended dose of ceftriaxone from 250 mg to 500 mg or 1 g in a single dose, depending on the patient's weight. Additionally, pharyngeal infection, which is often asymptomatic and may accompany infection at other sites, is more difficult to eradicate than urogenital or anorectal gonococcal infections and may serve as a reservoir of infection, possibly related to less predictable ceftriaxone levels in the pharynx. This consideration was another reason for the increase in the recommended dose. ​ Evaluation for cephalosporin resistance in patients with persistent or recurrent symptoms is essential to controlling the spread of drug resistance. Thus, all patients need to understand the importance of further evaluation if symptoms persist. The current recommendations also reflect a departure from prior recommendations for dual therapy of gonorrhea with ceftriaxone and azithromycin. Dual therapy had been theorized to reduce the risk of emergent resistance, based on evidence from other pathogens that demonstrated lower rates of resistance with the use of at least two agents that act upon different molecular targets. However, this was never demonstrated for N. gonorrhoeae, and in fact, treatment failure of a pharyngeal infection following dual therapy with subsequent decreased susceptibility to ceftriaxone and azithromycin has been reported. Decreasing susceptibility to azithromycin in N. gonorrhoeae and other organisms is now thought to outweigh any theoretical benefit. ​ Agents other than ceftriaxone are not appropriate as preferred regimens because of high rates of resistance. Clinical trials and novel therapeutics are urgently needed to identify the most appropriate treatment strategy for N. gonorrhoeae in the face of rising antimicrobial resistance. ​ Presumptive treatment for chlamydia — If concurrent C. trachomatis infection has not been excluded with molecular testing, presumptive treatment for chlamydia should be given at the same time as treatment for N. gonorrhoeae. We agree with CDC recommendations to use doxycycline (100 mg orally twice daily for seven days) for presumptive treatment of chlamydia in nonpregnant individuals with gonococcal infection. ​ First-line options for treatment of chlamydia are a course of doxycycline and single-dose azithromycin. Their relative benefits and drawbacks for treatment of chlamydia are discussed elsewhere. ​ In patients with gonococcal infection, we favor doxycycline over azithromycin. Increasing rates of decreased azithromycin susceptibility among N. gonorrhoeae isolates have been reported, and azithromycin exposure has been associated with high azithromycin MICs in N. gonorrhoeae.

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REF. UpToDat 2021.03.04

Update to CDC’s Treatment Guidelines for Gonococcal Infection, 2020