Antimicrobial stewardship and infection control: July 2018

Urgent care centers and emergency departments are prescribing and misprescribing antibiotics at a greater rate than traditional medical offices. This retrospective cohort study examined data from more than 150 million outpatient visits in an insurance claims database, comparing ICD-9 codes and associated antibiotic prescriptions with a focus on prescribing for antibiotic-inappropriate conditions (e.g; viral respiratory infections). The authors found that antibiotic prescriptions occurred in 39% of urgent care center visits, 36% of retail clinic visits, 14% of ED visits, and 7% of medical office visits. When only examining visits coded for antibiotic-inappropriate conditions, the authors found antibiotics were misprescribed in 46% of urgent care center visits, 24% of emergency departments, 17% of medical offices, and 14% of retail clinics. There is already a large body of literature showing that antibiotic stewardship in the emergency department is both feasible and impactful. Data like these suggest there is an urgent need for the same efforts in urgent care centers. 30014128

Antimicrobial stewardship in the ICU is safe. This systematic literature review examined 11 studies introducing audit and feedback into the intensive care unit. A meta-analysis of five studies that reported the effects of the ASP intervention in the ICU showed no difference in mortality (RR 1.03, 95% CI 0.93-1.14), as did a meta-analysis of the three studies that reported the effect on mortality only in the patients directly assessed by the ASP program (RR 1.06; 95% CI 0.8-1.4). One might argue that the ICU is where antibiotic stewardship to prevent the spread of MDR organisms is most important – after all, that’s where all the people who need reliable empiric antimicrobial therapy hang out. 29982376

Three out of every four antibiotic prescriptions in US primary care are inappropriate. I think we all know that antibiotic misuse is rampant across medicine, but the degree here is staggering. The authors randomly sampled outpatient antibiotic prescriptions from a Veterans Affairs primary care clinic at a large and well-respected academic medical center (n=3880), examining the appropriateness of each prescription. In 50% of cases, no antibiotic was indicated, in 12%, the wrong antibiotic was chosen, in 14% the wrong duration was given, and in 6% no reason at all was documented for the prescription. In total, 76% of antibiotic prescriptions were inappropriate. More than one third of antibiotics were prescribed without a face-to-face patient encounter. MDs and DOs, internists and family medicine-trained physicians, physicians and midlevel providers, and men and women were all equally bad at prescribing antibiotics. Azithromycin and ciprofloxacin were most likely to be misprescribed, which I suspect reflects acute respiratory infection and UTI being two of the most common infections seen in clinic.

Seems to me that if you’re running an antimicrobial stewardship program, the primary care clinics and particularly overuse of quinolones have to be a focus of your efforts. There’s clear guidance from the FDA that quinolones should be considered the drugs of last resort for nonsevere infections like ARI and UTI, and we know that quinolone resistance is associated with ESBL carriage and other antibiotic resistances in Enterobacteriaceae, so quinolone overuse is low-hanging fruit. 29967028

Controlling what microbiology data automatically ends up in the hands of clinicians is an effective way to influence their prescribing habits. The value of information control in stewardship has been shown in a variety of contexts, such as adding guidance statements to microbiology lab reports, only reporting the susceptibilities of antibiotics you want clinicians to prescribe, and throwing up ‘nuisance barriers’ like insisting the providers make a call to the lab to get culture data. This study examined taking the last approach for urine cultures to reduce treatment of asymptomatic bacteriuria (ASB). 110 consecutive hospitalized patients who were not catheterized, pregnant, or in the ICU were randomized to standard reporting of their urine cultures or a statement to the effect of ‘the culture is positive and could be ASB or a UTI; call us for the specific results if you suspect UTI clinically.’

The proportion of appropriately treated urine cultures was higher in the modified report arm than in the standard report arm (80% vs 53%; p=0.002), with a number needed to benefit of 3.7. As you might imagine, the improvement in appropriateness was mediated by a substantial decrease in treatment of ASB (37% vs 59%). No adverse events were observed in the modified reporting arm, and in fact undertreatment of UTI was nonsignificantly HIGHER in the standard reporting arm. The authors noted that patients whose bacteriuria was appropriately managed (e.g. treatment of UTI and nontreament of ASB) had significantly shorter stays than those whose bacteriurias were improperly managed, an association that has been previously shown in other studies. All in all, this is a cheap and safe intervention that significantly improves antimicrobial use in the inpatient setting. 29804552

While we are on the subject, a similar paper looking at the influence of sputum culture reporting on antibiotic prescription for pnuemonia was published in OFID this month, though I haven’t seen it appear in PubMed yet. In this before/after intervention study, the authors added a comment specifying that MRSA and Pseudomonas had not been isolated when sputum cultures yielded mixed growth without either organism. The study included four hospitals and a total 210 patients. De-escalation or discontinuation of drugs for MRSA and Pseudomonas occurred significantly more frequently after the addition of the reporting comment (in 73% vs 39% of cases), and in multivariate analysis the change in reporting was associated with a 5.5-fold increase in odds of antimicrobial de-escalation. AKI occurred less frequently after the intervention, and mortality rates were unchanged. Reference here.

This meta-analysis suggests that probiotic prophylaxis may decrease the odds of C. difficile infection. My gut reaction (get it?) has long been that the use of probiotics in CDI is silly. The human GI microbiome is composed of thousands of bacterial species; devastating it with broad-spectrum antibiotics and then giving some Bifidobacterium is the microbial ecologic equivalent of carpet bombing the Amazon and then planting a giant corn field and declaring it remediated. But we ought to follow the evidence, and this meta-analysis of 18 RTCs totaling 6851 patients suggests that probiotic prophylaxis may decrease the incidence of CDI in hospitalized patients (pooled OR 0.35). The authors state that probiotics appeared safe, with no significant increase in adverse events versus controls, though I will point out that a recent systematic review in Annals of IM found that reporting of safety data for probiotics in clinical trials has been largely inadequate (reference here).

Probiotic prophylaxis appeared beneficial only when multispecies preparations were used and only when the baseline incidence of CDI was >5%. The latter point is stated indirectly (from the paper: “This analysis suggested that CDI incidence ≥5% interacts with the overall group effect, suggesting that probiotics may be more effective when the baseline CDI risk is moderate to high”), but it’s critical: many, perhaps most hospitals have a prevalence of CDI under 5%, so the benefit of routine probiotic prophylaxis in that setting is questionable. I wish the authors had explicitly given us the odds ratios and confidence intervals for CDI risk with probiotics versus no probiotics stratified by baseline incidence of CDI greater or less than 5%, and wonder whether the reason that data is missing is because the p value in low-incidence group was not significant.

I don’t know that this study changes my mind about routine probiotic prophylaxis for CDI, though I think it makes a more compelling case for giving probiotics to the patients at highest risk for CDI (i.e.; those in whom we would expect the baseline incidence to be >5%). One might argue that in the absence of better data, probiotics are inexpensive and probably safe, so they are likely to be cost-saving in high-risk patients even if the degree of risk reduction offered is modest. I am unaware, however, of any studies reporting the safety of probiotics in a large cohort of highly immunocompromised hosts - the very people who have the most trouble with recurrent CDI - and given the number of case reports of probiotic-associated bacteremias and fungemias we've seen in this patient population, I wonder about the safety of universal probiotic prophylaxis for these patients. 29695312