Thread by @DharSaty

Duration of Antibiotic Therapy
Deciding on the duration of antimicrobial therapy for an infection is neither straightforward nor simple. 👇
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Most ID guidelines are based- either expert opinions or evidence-based medicine. Historically, duration of ABX Rx were based on arbitrary extension of days(magic numbers like 7, 10 & 14 days) rather than on reliable evidence with the main aim to ⬇️ failures & avoid underRx.

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There is growing evidence to support for shorter courses. It is important for prescribers to be up to date with best practices. Duration of therapy plays a pivotal role in antimicrobial stewardship programme within the global effort to optimize antibiotic use &⬇️resistance.

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The evidence indicates that each day of ABX therapy beyond the first confers a⬇️additional benefit to clinical cure while⬆️the burden of harm in the form of adverse effects, superinfections, and selection of antibiotic resistance.

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ncbi.nlm.nih.gov/pmc/articles/P…

In a MRCT, pts with GN bacteremia & controlled focus received 7-14 days of ABX therapy. The primary outcome at 90days➡️all-cause mortality; relapse, suppurative or distant complications & re-admission or extended hospitalization did not vary.

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bmj.com/content/358/bm…

CHOICE OF AGENT
ABX are either bactericidal or bacteriostatic. Infections with a high bacterial burden, e.g., infective endocarditis, require Rx with ABX with rapid bactericidal activity. In most cases, more than 1 ABX is used to provide synergistic activity & rapid killing.

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Native valve IE by penicillin-susceptible S viridans, the usual Rx can vary from 2-4 wks. If penicillin G or ceftriaxone alone is prescribed, the Rx should be 4wks; however, if either ABX is used with an aminoglycoside, then the Rx can be⬇️ by 2wks.

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ahajournals.org/doi/10.1161/ci…

Efficacy of ABX➡️ability to penetrate & remain for an adequate time at the site. 3-day course of cefpodoxime, did not provide a similar cure rate as it did with a 3-day regimen of cipro (82% vs 93%; 95% CI, 3%-18%) for the RX of acute uncompl cystitis.
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jamanetwork.com/journals/jama/…

TYPE AND SEVERITY OF INFECTION
Pt’s immune status, anatomical site, & pathogen causing the infec should be considered when assessing duration of Rx. CAP can be Rx in 5 days, but once complicated by bacteremia or severe sepsis, a longer is essential.

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pubmed.ncbi.nlm.nih.gov/17278083/

The ability of ABX to penetrate necrotic tissues, abscesses, or biofilms can limit efficacy. Infec can be difficult to treat & require prolonged ABX courses. Unless surgical intervention is undertaken to remove debris &/ or drain abscesses, ABX cannot reach infected sites.
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A course of ABX for intraabdominal infections is no longer than 7 days; however, if it is difficult to perform the source control procedure (eg, drain infected foci, control ongoing peritoneal contamination), a longer treatment course is necessary.
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pubmed.ncbi.nlm.nih.gov/20034345/

ASSESSMENT OF PATIENT’S RESPONSE
El Moussaoui et al found that discontinuing ABX 3 days after /s resolution did not adversely affect patient outcomes. There were no differences in clinical or radiological outcomes - the 2 groups after 10 & 28 days.

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pubmed.ncbi.nlm.nih.gov/16763247/

Rechecking Cx is not necessary once response, except in bacteremia. Monitor for clearance is crucial➡️day1 of ABX Rx is the first day on which -ve bld Cx are obtained. Unnecessary Cx should be avoided, +ve cx with no s/s leads Rx colonized bacteria.

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pubmed.ncbi.nlm.nih.gov/19489710/

ABX, in general, are safe, but have risks associated, including the development of allergic rxn, C difficile infection, antibiotic resistance, & cost. It is important to provide a substantial Rx course so that an infection is treated adequately & relapse is prevented.

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CRP & procalcitonin has been instrumental in evaluating response & determining the duration of Rx. Procalcitonin guided algorithm has been shown to reduce the duration of exposure by ≤25% in pts with lower respiratory infect & 23% in critically ill.

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pubmed.ncbi.nlm.nih.gov/20097417/

Current guidelines recommend at least 7–14 days, although no RCT have evaluated the optimal duration for central venous catheter-related bacteremia due to Gram-negative bacilli. Recent data suggest 7days or less may be as well tolerated & effective.

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pubmed.ncbi.nlm.nih.gov/31259864/

Ventilator-associated pneumonia is the most common & serious hospital-acquired infec reported in pts on mechanical ventilation. Infectious Diseases Society of America & the American Thoracic Society now recommend a 7-day course of ABX for such pts.

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pubmed.ncbi.nlm.nih.gov/28149576/

The main advantages of shorter courses is to⬇️MDR pathogens & prevent the emergence of resistance. Chastre et al., compared 2 ABX regimens for pts with VAP (8 vs.15 days):MDR emerged less frequently in those with longer Rx (42.1% vs. 62.3%; P=0.04).

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jtd.amegroups.com/article/view/1…

GN bacilli, Acinetobacter sp. similar to Pseudomonas sp. create a biofilm, have a⬆️of intrinsic resistance & have ways to develop & transfer resistance. Short course was associated with⬆️recurrence (41.8 vs. 24.7%). A 7d treatment may not be enough.

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ccforum.biomedcentral.com/articles/10.11…

Endotracheal colonization is common in ICU & represents a continuum to VAP, & is not equivalent to infec of distal airways. Appropriate Rx can eradicate colonization by S. pneumoniae, H. influenzae, and S. aureus, but fails to eradicate Enterobacteriaceae and P. aeruginosa.

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In a study of neutropenic fever, empiric ABX was safely discontinued after 72hrs of apyrexia in the intervention grp vs control grp in which empiric ABX was continued until 72Hrs of apyrexia & resolution of neutropenia. All-cause MR was not different.

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pubmed.ncbi.nlm.nih.gov/29153975/

Pts with MRSA complicated SSTI, in addition to surgical debridement & broad-spectrum abx, empirical therapy for MRSA should be considered pending culture data. 7-14 days Rx is recommended but should be individualized on the basis of the pt's response.

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academic.oup.com/cid/article/52…

MRSA bacteremia & IE, Native Valve:

- For adults with uncomplicated bacteremia, for at least 2 weeks.
- For complicated bacteremia, 4–6 weeks of therapy is recommended, depending on the extent of infection.
- For adults with infective endocarditis, 6 weeks is recommended.

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Infective Endocarditis, Prosthetic Valve:

- IV vancomycin plus rifampin 300 mg PO/IV every 8 h for at least 6 weeks plus gentamicin 1 mg/kg/dose IV every 8 h for 2 weeks.
- Early evaluation for valve replacement surgery is recommended.

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academic.oup.com/cid/article/52…

SUMMARY
Recent years have seen a consistent trend toward shorter ABX durations for many infec syndromes including pneumonia (CAP & nosocomial), cystitis, complicated UTI, intraabdominal infec, acute bacterial sinusitis, cellulitis & STI, septic arthritis & osteomyelitis.

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