さまよう薬剤師のブログ

学位を持っても、センスのない、感染制御専門薬剤師のブログ.  I have Ph.D. but less sense ID pharmacist. Another face is an investor.

Procalcitonin and antibiotic use: imperfect, yet effective

LIDに報告された、プロカルチンと抗菌薬についてのコメント

http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(17)30593-5/fulltext

 

Effect of procalcitonin-guided antibiotic treatment on mortality in acute respiratory infections: a patient level meta-analysis

http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(17)30592-3/fulltext

 

 

このメタアナに対するコメントです。

 

The overwhelming burden of acute respiratory infections is undeniable. An estimated 2·74 million people died of lower respiratory tract infections in 2015 worldwide. Despite being commonly caused by viruses, antibiotics are often used to treat these diseases. In the USA, around 40 million outpatients received antibiotics for respiratory infections in 2007–09.

In adults, it is extremely challenging for physicians todi erentiatebetweenbacterialandviralrespiratory tract infections, as well as exacerbations of other chronic respiratory diseases, because of the overlap of clinical ndings and abnormalities seen in ancillary tests. This di culty in di erentiation unequivocally leads to antibiotic overuse in this population of patients.

In the literature it is reported that the appearance of resistant bacterial strains is driven not only by antibiotic use per se, but also by prolonged duration of treatment.  By contrast with other diseases such as systemic hypertension, in which clinical management can be personalised according to patient needs, the treatment of bacterial infections still follows a one-size- ts-all model. This approach is used because traditional diagnostic methods are not able to identify in real-time the moment when infections have been eradicated and antibiotics are no longer needed. To overcome this limitation, the use of procalcitonin has been proposed.

Procalcitonin is a prehormone that seems to act as a mediator in in ammatory processes. Despite not being perfectly speci c for bacterial stimuli, procalcitonin concentrations rise and fall in a pattern most consistent with infection and its subsequent resolution, and are positively associated with the severity of the infectious process.  Several randomised controlled trials (RCTs) have successfully shown that procalcitonin-guided treatment algorithms reduce antibiotic use for acute respiratory tract infections in adults. However, questions regarding the safety of procalcitonin-guided treatment remain.

The meta-analysis by Philipp Schuetz and colleagues,  published in The Lancet Infectious Diseases, con rms the aforementioned results of individual RCTs while showing that the use

of procalcitonin algorithms was not associated with antibiotic treatment failure or increased mortality.  In fact, the risk of 30-day mortality was signi cantly lower in the procalcitonin-guided group than in control patients (286 [9%] deaths in 3336 procalcitonin-guided patients vs 336 [10%] in 3372 controls; adjusted odds ratio [OR] 0·83 [95% CI 0·70–0·99], p=0·037), which could be explained by a reduction in antibiotic-related side-e ects, including Clostridium di cile colitis. Having included 26 RCTs and used individual patient data from 6708 participants, this study is well positioned to shed much needed light onto the safety of procalcitonin-guided antibiotic use for patients with acute respiratory tract infections in di erent settings.

Nevertheless, important challenges still remain regarding the widespread use of procalcitonin to tailor antibiotic treatments. The di erent procalcitonin cuto concentrationsusedinRCTsleadtouncertainty regardingtheirrespectivesafetyandcreateconfusion forhospitalsaimingtoimplementalocalprogramme. Moreover, procalcitonin algorithms that are solely based on biomarker concentrations can be very challenging for clinicians to follow. This problem is especially true when the algorithm recommends the non-initiation of antibiotics in severely ill patients with suspected bacterial infection, for whom a delay in starting treatment is associated with increased mortality risk.  Studies show that disease severity prompts physicians not only to use antibiotics, but also to extend treatment duration.  The fear that early stopping of antibiotics might lead to resistance- conferring mutations in bacteria causing an infection is also a challenge. Although selection of mutated infecting strains is a well described pathway to resistance, antibiotic treatments more frequently drivebacterialresistancebycausingso-calledcollateral damage to the host’s normal microbial ora, resulting in the selection of resistant commensal strains. Finally, evidence regarding the e ectiveness and safetyofusingprocalcitonintotailorantibioticusein paediatricandneonatalpatientsisstillscarce.

The use of procalcitonin-guided treatment in adult patients with acute respiratory tract infections effectively reduces antibiotic consumption without being associated with an increased risk of treatment failure or mortality. Therefore, will procalcitonin solve the antibiotic overuse problem in this patient population? No, it will not. Although procalcitonin provides important information about a potential bacterial cause and the resolution of bacterial processes, the clinical reasoning behind antibiotic- related decisions is also strongly in uenced by patient and disease characteristics, such as severity, and physicians’ previous experiences, which can easily override any algorithm recommendation. Nevertheless, we should not be looking for perfection when dealing with antibiotic overuse, but for strategies that can mitigate the global bacterial resistance problem. Thus, if procalcitonin can safely decrease unnecessary antibiotic use in di erent settings, even if imperfectly, it is already worthwhile.

 

この中で、筆者は以下のように述べてます。

 

Therefore, will procalcitonin solve the antibiotic overuse problem in this patient population?

No, it will not. Although procalcitonin provides important information about a potential bacterial cause and the resolution of bacterial processes, the clinical reasoning behind antibiotic- related decisions is also strongly in uenced by patient and disease characteristics, such as severity, and physicians’ previous experiences, which can easily override any algorithm recommendation.

Nevertheless, we should not be looking for perfection when dealing with antibiotic overuse, but for strategies that can mitigate the global bacterial resistance problem. Thus, if procalcitonin can safely decrease unnecessary antibiotic use in di erent settings, even if imperfectly, it is already worthwhile.

 

私も同感です。患者の重症度、場所、原因微生物の特定プロセスを経て、使用を考慮すべきでしょう。

CRPのような盲目的なツールになっては、良さが減少してしまいます。

 

プロカルについて、動向をチェックしていきます。