書きかけ。

テーマ:
ICMから、もう一個だけ。

When antibiotic treatment fails

永遠の課題。
抗生剤の治療失敗、、、、と対処、ってか。
抗生剤治療が失敗したら、どうする?
そしてそれは、いつ、どのように判断する⁈
、、、、、
明確な判断、、、、難しいですよね。

抗生剤使用後、早期に、
反応がある、反応がない、と判別することは非常に重要だろう。

ただ、治療失敗を決定する決まり、自体はまだ定義がないんだよね。
つまり、殆どは、臨床的客観的事実からの判断、となっている。
プラスで、少々、医者の決定事項、で判断されている。

判断は、早期である必要がある。
しかし、早すぎても、臨床的反応が十分でない可能性がある。

しかし、反応の速さは、感染の部位、原因菌、患者免疫で、変わって来る。
異なる症状、患者ごと、異なる時間が必要だと。
一般に、48ー72時間程度、と思われる。

治療に対する反応は、
臨床的、生化学的、微生物学的に評価できる。
臨床的には、熱下がる、脈落ち着く、意識良くなる、など。
検査的には、WBC、CRP、プロカル、などが下がる。
臓器としては、昇圧剤下がる、酸素化改善、など。
放射線的には、膿瘍縮小、肺が広がる、など。
ただ、
放射線的な評価は、臨床的改善に遅れて現れることが多いけどね。
ルーチンな放射線が必要ない、ってのは良く知られた概念だよね。

臨床的反応は、評価には適している。
しかし、良く用いられる、
Xp評価、浸出液の性状、熱、WBC、などは、
実際には、治療反応性に適していない、という報告もある。
一方で、
P/F Ratioなどの臓器特有の評価法の方が、
実際の反応として有効だ、とする報告もある。
放射線が完全な改善を認めるには、数週間〜数ヶ月、を要する。

細菌が、微生物学的に最も出会う頻度が高い。
血液感染で全身へ行かなくするのは、臨床的改善と同様に重要だ。

遷延する細菌は、時に、不十分な原発巣治療、複雑な血行感染(IE、カテ)、
を示す唯一の手がかりのことがある。
感染の遷延は、耐性菌の出現にもつながり、評価されるべき。

『MALDI-TOF 』、『antimicrobial stewardship』、 賢明な選択、
を、特定層に行うと、抗生剤の早期正確投与に繋がる。

解熱され、臨床的安定があり、SOFAスコアが減っているか、
ってのを抗生剤の効果判定に使う。
通常、開始から48ー72時間後が良いとされる。


Although CRP and PCT kinetics in the rst 3–4 days of therapy may help to identify patients with a complicated course [9], a biomarker-based strategy failed to improve outcome as compared to usual care. erefore, a strategy of antibiotic escalation based exclusively on PCT or CRP results should be discouraged [10].

In the face of absence of response to empirical antibi- otic therapy, microbiological results must be considered and if rst-line therapy was inappropriate, the antibiotic should be changed swiftly. In fact, the spread of mul- tidrug-resistant infections is leading to an increase in empirical antibiotic treatment failure.
However, antibiotic inappropriateness is neither the only nor the more common cause of therapy failure [11]. If microbiological results show that an antibiotic regimen (that is now de ned “targeted”) is appropriate or if they are inconclusive, several other causes of therapy failure must be considered, namely: wrong diagnosis (non-infec- tious disease), development of infectious complication, persistence of in ammation, inadequate source control, antibiotic pharmacokinetic and pharmacodynamic (PK/ PD) issues and host immunosuppression [12]. Failure to respond to antibiotics includes also the emergence of resistant organisms, superinfections and drug interac- tions. e most common mistake made with apparent antibiotic failure is to change or add antibiotics. e most important strategy is to analyze the cause of the antibi- otic failure by careful evaluation and use of appropriate diagnostic tests to avoid needless, and expensive and potentially dangerous antimicrobial therapy (see Fig. 1).
Apart from in vitro antimicrobial activity and achievement of adequate serum levels, the e cacy of

antimicrobial agents depends on their capacity to achieve a concentration equal to or greater than the minimum inhibitory concentration (MIC) at the site of infection. Antimicrobial concentrations attained at some sites [e.g., ocular uid, cerebral spine uid (CSF), abscess cav- ity, prostate and bone] are often much lower than serum levels. For example, rst- and second-generation cepha- losporins and macrolides do not cross the blood–brain barrier and are not recommended for CNS infections. Daptomycin, an excellent bactericidal agent against gram-positive bacteria, is not useful for treatment of pneumonia (e.g., pneumococcal pneumonia) because it is inactivated by a lung surfactant e presence of for- eign bodies at the site of infection also a ects antimicro- bial activity. Other potential causes of treatment failure include the wrong dosaging of antimicrobials, particu- larly important in certain patient populations such as the critically ill. Unfortunately, monitoring of antimicrobial drug concentrations is not available routinely for most compounds in most of the hospitals, and remains a sort of a “dream” for many physicians. ese tools would enable intensive care specialists to adjust for the contin- uous changes in volume of distribution and drug clear- ance that occur in the critically ill. e increased volume of distribution that follows and glomeral hyper ltra- tion associated with severe sepsis and septic shock lead
to low plasma concentrations of antimicrobials. In turn, attempts to correct for underdosing may be o set by the development of renal or hepatic dysfunction.
Antimicrobial therapy is usually, but not always, the most important therapy for infectious diseases; however, there are many “non-antimicrobial therapies” that may avoid treatment failure. e best-recognized example of non-antimicrobial therapy in the treatment of infec- tions is “source control”, namely the use of operative drainage or debridement. is procedure is useful when the organism burden is very high or in the management of abscesses, for which the penetration and activity of antimicrobial agents are often inadequate. Other thera- pies used in the treatment of infectious diseases involve modulating the host in ammatory response to infection. Systemic corticosteroids, thought to act by decreasing the deleterious e ects of the host in ammatory response, have been found bene cial when used in conjunction with antimicrobial therapy for the treatment of bacterial meningitis, tuberculous meningitis and pneumocystis pneumonia in patients with AIDS. Temporary discontin- uation or dose reduction of immunosuppressive agents is often required for successful treatment of infections in organ transplant recipients or patients with rheuma- tologic disorders. Intravenous immunoglobulin therapy, which acts to neutralize toxin produced by the bacteria, can be used in addition to surgical debridement and anti- microbial therapy in the treatment of necrotizing fasciitis caused by group A streptococci and severe toxic shock syndrome. Some of these interventions lack a strong evi- dence base but are often recommended by experts on the basis of clinical experience.
In conclusion, we believe that adequate and timely assessment of response to treatment and awareness of antibiotic failure may potentially increase the qual- ity of treatment and improve outcomes. New molecular and rapid diagnostic tools may play a signi cant role in reducing the time for de ning failure, for adjusting treat- ment and, consequently, for improving prognosis of seri- ous infections.


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