Friday, July 08, 2022

Myths and facts in antibiotic stewardship

The current issue of the American Journal of Medicine (the Green Journal) has an article titled Top Myths of Diagnosis andManagement of Infectious Diseases in Hospital Medicine. This is one of the better articles pertaining to antibiotic stewardship that I have seen. Ten myths are listed. They are not complete myths (exceptions apply to just about all of these principles); rather, they are misconceptions.

Myth one: antibiotics do no harm. High-level data refute this myth. For example, a recent metaanalysis showed that the use of procalcitonin guidance to shorten the duration of antibiotic therapy was associated with lower mortality.

Myth two: antibiotic durations of 7, 14, or 21 days are typically necessary. Although these are common recommendations, evidence is lacking. In many situations (and there are exceptions) shorter duration therapy is as good as longer duration. Examples include 3 to 5 days for community acquired pneumonia; eight days for nosocomial pneumonia; 5 to 7 days for pyelonephritis; four days for intraabdominal infection; five days for acute exacerbations of COPD and 5 to 6 days for cellulitis. There are notable exceptions. Certain deep-seated and difficult to eradicate infections are not candidates for either shorter duration or procalcitonin guidance for discontinuation. These include tuberculosis, meningitis, prosthetic joint infections, staphylococcal bacteremia, endocarditis and invasive fungal infections. The same caution applies to some immunocompromised patients.

Myth three: if one drug is good two (or more!) must be better. This requires nuance.There are some indications for combination therapy. They are exceptions rather than the rule. The main indication for combination therapy is initial empiric treatment for life-threatening infection such as sepsis. The rationale is to cover all likely pathogens. De-escalation is appropriate if and when culture and sensitivity results indicate that a single agent would be appropriate. This principle is also applied in meningitis where in patients 50 years of age or older we include listeria coverage such that in non pen allergic patients ampicillin is added to the combination of ceftriaxone and vancomycin. Also in meningitis the combination of ceftriaxone and vancomycin accommodates the possibility of relative resistance of strep pneumo which might cause treatment failure with cephalosporin monotherapy. In community acquired pneumonia requiring hospitalizations the guidelines call for combination cephalosporin and macrolid therapy. For patients admitted to ICU it is recommended that MRSA coverage be added (this is in the IDSA MRSA guideline, not the pneumonia guidelines).

A frequently asked question is what to do about serious gram negative infections. Traditionally “double coverage“ with two gram-negative agents has been used. For the most part this is not supported by evidence. One exception is in the initial (empiric) antipseudomonal coverage for HAP/VAP., the guidelines for which indicate double coverage initially which should be de-escalated later if microbiologic data allow. In contrast, the CAP guidelines for patients with pseudomonas risk recommend monotherapy---not double coverage--from the start.

Myth four: oral antibiotics are not as good as IV antibiotics for hospitalized patients. This is, in general, a myth but there are exceptions. IV therapy is not inherently better than oral if there’s adequate bioavailability with the oral agent and if susceptibilities allow switch to an oral agent. Cautions apply in bacteremia. Some of these (eg staphylococcal bacteremia ) require intravenous therapy for the entire course. In other bacteremic infections step down to oral agents may be appropriate. Examples include certain streptococcal bacteremias and gram-negative bacteremic urinary tract infections. In such cases a switch to oral therapy can be considered as early as day four.

Myth five: bacteria in the urine signifies a UTI and should be treated. If it is asymptomatic treatment is only warranted in pregnancy and patients about to undergo a urologic procedure.

Myth six: history of penicillin allergy means the patient can never receive a beta lactam antibiotic. Former thinking was that there’s a 10 to 15% cross sensitivity rate between penicillin and cephalosporins. More recent findings indicate that the cross sensitivity rate to penicillin allergy is more like 3% for cephalosporins and 1% for carbapenems. The article provides some general principles for decision making in patients with purported penicillin allergy. For reactions that are mild and non specific a cephalosporin can be given. If the reaction was anaphylactoid either an alternative antibiotic to a cephalosporin or penicillin desensitization is recommended. Severe non anaphylactic reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis and DRESS syndrome are in a different category. In those cases the use of any beta lactam is contraindicated as is penicillin desensitization.

Myth seven: antibiotics for surgical prophylaxis should be continued for 24 hours or more .

Myth eight: antibiotics must be continued for as long as drains are in place. Although clinical judgment is required here there is no robust evidence to support such a practice.

Myth nine: nitrofurantoin can be used for UTIs only if the creatinine clearance is greater than 60. This is in accordance with product labeling but the data indicate 30 may be more reasonable cut off.

Myth ten: fluoroquinolones are first line agents for many infections. We now have mounting evidence of adverse effects (CNS toxicity,, tendon rupture, dysglycemias, irreversible neuropathy, QT prolongation and aortic dissection) such that fluoroquinolones have been relegated to a lower position in the sequence. They should be used only when safer and equally effective alternatives are not available.

In a related antibiotic stewardship topic this article from Cinical Infectious Disease looked at the utility of MRSA PCR screening. Negative PCR can allow for discontinuation or avoidance of MRSA therapy such as vancomycin in many situations. Those studied in the article were bloodstream infections, intra-abdominal infections, respiratory infections, wound infections and urinary tract infections. Negative predictive value was 93% or better in all those situations.