January 2019: Antimicrobial stewardship and infection control

Contact isolation precautions do not prevent acquisition or transmission of MDR E. coli in cancer wards.  The authors performed a prospective, multicenter cohort study across four German oncology departments, two of which placed patients with MDR E. coli (resistant to quinolones and 3rd-gen cephalosporins) on single-room contact isolation precautions, and two of which did not.  Patients in each ward were screened for MDR E. coli carriage on admission, weekly, and at discharge, and molecular typing was done to identify specific transmission events.  The primary outcome of interest was the prevalence of carriage of MDR E.coli.

The study included a total 2,968 patients over a 12-month period.  In the no contact precautions versus contact precautions wards, Hospital acquisition of MDR E. coli occurred in 1.6% vs 1%, bloodstream infection occurred in 0.2% vs 0.3%, and patient-to-patient transmissions occurred in three patients each (p > 0.05 for all).  The authors calculate that 3729 patients would need to be screened (and a total 24,274 tests would need to be sent) in order to prevent a single patient-to-patient transmission of MDR E. coli.

Probably the Germans have better ways to spend their healthcare dollars.  30641228

Empiric antimicrobial treatment is mostly unnecessary for complicated UTIs (cUTIs) diagnosed in the hospital.  It turns out that, much like in the outpatient world, urinary tract infection is a leading driver of antibiotic prescription in the hospital.  This multinational, multicenter retrospective cohort study included hospitalized patients with cUTI over a 1-year period (total n=981).  The primary outcome was treatment failure; 30-day mortality was a secondary endpoint.

Treatment failure occurred in 27% of patients, and the all-cause 30-day mortality rate was 9%.  In a multivariate model, risk factors significantly associated with treatment failure included ICU admission (OR 5.1), having metastatic cancer (OR 2.9), being bedridden (OR 2.1), septic shock (OR 1.9), steroid treatment (OR 1.9), and having a catheter-associated UTI (OR 1.5).  Neither appropriateness of empiric therapy nor time to starting antibiotics associated with either treatment failure or mortality. 

Hence, early and aggressive antibiotic treatment of cUTI does not appear to offer much clinical benefit, and in patients who are clinically stable, clinicians should instead consider supportive care and watchful waiting until the causative organism and its susceptibilities are known. 29788118

This small cohort study adds to the literature demonstrating that people with a history of injection drug use can still be good candidates for OPAT.  As we’ve discussed before in our journal club, many clinicians find the suitability of people who use injection drugs (PWID) for outpatient parenteral antimicrobial therapy (OPAT) controversial, with concerns that PWID will inject drugs through their lines or be lost to followup and suffer complications from having their lines stay in place.  However, the data on this subject is quite scant, and what does exist does not support a meaningful difference in outcome between people who do versus do not inject drugs.

The authors reviewed the medical records of PWID treated with OPAT at their center over a 2-year period.  At this medical center, PWID are eligible for OPAT if they have adequate social support at home, have multiple points of contact (i.e. phone #s for them and a family member), have not engaged in aggressive behavior during the inpatient stay, and are not using crystal meth (due to frequent aggressive behavior in this group).  For harm minimization, PWID receive addiction counseling and a “PICC filter” to use if they do inject drugs through the PICC.  The researchers defined OPAT treatment success – their primary outcome – as having finished the initially planned duration of IV therapy and experienced clinical improvement. 

Thirty-eight cases of OPAT in PWID were included in the cohort, among which the median duration of treatment was 14 days, for a total 778 nursing visits to a variety of settings (e.g. patient’s home, workplace, or a supermarket parking lot).  The median age was 37, a quarter of patients were on opioid replacement therapy, and 37% had used injection drugs in the past month. Osteomyelitis and endovascular infections made up the bulk of the infections, and S. aureus was the causative pathogen in nearly half.  A total 28/38 (76%) of the cases were treated successfully; the rate was highest (83%) in patients who had not used injection drugs in the preceding year.  Among the ten patients who did not complete OPAT, four were lost to followup and six were readmitted to the hospital and not restarted on OPAT.  In terms of complications, new polymicrobial bacteremia related to ongoing drug use occurred in three cases, and nine patients had a total 14 re-admissions for new bacteremia, need for additional source control procedures, and medication side effects, respectively.  For reference, the medical center’s general OPAT population had a re-admission rate of 10%.

In conclusion, PWID can be effectively treated with OPAT, though higher rates of complication and re-admission are to be expected.  I would note here that PWID are probably more likely to have more complications and re-admissions regardless of how you treat their infections, because they often continue to use injection drugs, so when thinking about whether to offer PWID OPAT, the question we should focus on is not whether they’ll do as well as someone who doesn’t use drugs, but whether they’ll do as well as if we asked them to stay in the hospital.  30680563

Cephalosporin use is an important target for reducing the incidence of C. difficile in your hospital.  This is important because ceftriaxone and cefepime are two of the most commonly used drugs for empiric coverage of gram-negative bacteria.  It also makes total sense, because cephalosporins are otherwise broad-spectrum antibiotics that have very little activity against anaerobes (hence why the second-gen cephs with anaerobic activity, cefoxitin and cefotetan, are actually their own class - cephamycins. Also hence why the cephalosporin-based beta-lactamase inhibitor combo drugs – ceftazidime-avibactam and ceftolozane-tazobactam – have poor anaerobic activity and need to be combined with metronidazole for intra-abdominal infections).  So, in giving a cephalosporin, you’re carpet-bombing the patient’s gut flora – except for C.difficile and friends – and providing a nice ecologic niche into which C.diff can expand.

The authors retrospectively compared two hospitals in Sweden, one of which instituted an antibiotic stewardship program with a focus on reducing cephalosporin use, before and at two points after the antibiotic stewardship program’s initiation.  The two hospitals were of similar size, had similar infection control policies, and neither experienced a C. difficile outbreak during the study period.  The outcome of interest was the incidence of C. difficile infection (CDI), defined as a positive toxin immunoassay; there were some minor differences in the tests used at each hospital, which I won’t belabor except to say I think the investigators accounted for them adequately (i.e.; go read the methods yourself if you care).

At the ASP hospital, cephalosporin use decreased 86% after the intervention and was replaced by piperacillin-tazobactam, benzylpenicillin, and cloxacillin, each in more or less equal measure. Interestingly, rates of pip-taz and benzylpenicillin also modestly increased at the non-ASP hospital - I wonder if that reflects cultural influence within a small community of ID docs?  Anyway, at the ASP hospital the CDI rate per 1,000 hospital admission decreased from 2.3 in 2007 to 1.2 in 2015 (p = 0.0014); at the non-ASP hospital, the CDI rate was unchanged (2.1 in 2007 to 2.4 in 2015; p > 0.05).  While the rate of CDI between the two hospitals was no different in 2007, it had become lower at the ASP hospital by 2015 (1.2 vs 2.4; p=0.0002).

When the authors looked at antibiotic exposures in the preceding 30 days for each case of CDI in 2007, they found that ~30% were associated with a cephalosporin at both hospitals, and that most of these were specifically associated with cefuroxime.  When they pooled all antibiotic exposure data to try to identify the antibiotics most associated with CDI (with data weighted by antibiotic use), they found the most associated drugs to be cefotaxime, cefuroxime, clindamycin, ceftibuten, and levofloxacin, with cefotaxime conferring far more risk than the other drugs.

Until reading this paper, I hadn’t really appreciated how much CDI risk late-gen cephalosporin use conferred; I’d been taught that clindamycin and quinolones were the two C.difficile boogiemen. I highly recommend giving Figure 4 a look, as it nicely compares the risk of the 29 antibiotics given in the month preceding the CDI diagnoses.  30358837