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Snapshots From ID Week, October 3 to 7, 2018

Louie, Ted, MD*; Aziz, Andrew, PharmD, BCPS

Infectious Diseases in Clinical Practice: January 2019 - Volume 27 - Issue 1 - p 1–2
doi: 10.1097/IPC.0000000000000701
IDC Snapshots
Free

From the *Robert Wood Johnson-Rutgers and

Clinical Pharmacy Specialist, Infectious Diseases, St. Peter's University Hospital, New Brunswick, NJ.

Correspondence to: Ted Louie, MD, 579A Cranbury Road, East Brunswick, NJ 08816. E-mail: tlouie88@gmail.com.

The authors have no funding or conflicts of interest to disclose.

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1. ORAL ABSTRACTS SESSION 30, OCTOBER 4, 2018. ABSTRACT 111. STRYMISH JM, O'BRIEN W, ITANI K, GUPTA K. INCREASING DURATION OF SURGICAL PROPHYLAXIS INCREASES ANTIMICROBIAL—ASSOCIATED ADVERSE EVENTS BUT DOES NOT DECREASE SURGICAL SITE INFECTIONS: AN OPPORTUNITY FOR STEWARDSHIP

The authors studied 79,092 patients in a multicenter study involving Veterans Affairs patients undergoing cardiac, total joint, vascular, and colorectal procedures between 2008 and 2013 and reviewed length of prophylaxis, incidence of skin and soft tissue infections, and complications attributed to antibiotics. After adjusting for type of surgery and other factors, they concluded that longer duration of antibiotics beyond the recommended 24 hours did not reduce surgical site infection. On the other hand, the incidence of acute kidney injury and Clostridium difficile significantly increased with each 24-hour period.

Comment: For effective surgical prophylaxis, the key is an adequate tissue level of appropriate antibiotic at the time of incision. Standard guidelines for surgical antimicrobial prophylaxis stipulate that antibiotics be stopped within 24 hours. However, some institutions have been slow to implement standard guidelines, and many institutions face the challenge of individual physicians deviating from accepted practice, whether from lack of education, or from a belief that their patients are different. Strymish et al have armed antibiotic stewards with additional data to bolster the rationale for adhering to standard antibiotic prophylactic regimens.

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1. POSTER SESSION 52, OCTOBER 4, 2018. POSTER 245: HOFFMAN M, COUNTERMAN K, QUERFURTH S, HOLLENBECK B. ELIMINATION OF ROUTINE URINALYSIS BEFORE ELECTIVE ORTHOPEDIC SURGERY REDUCES ANTIBIOTIC UTILIZATION WITHOUT IMPACTING CATHETER-ASSOCIATED URINARY TRACT INFECTION OR SURGICAL SITE INFECTION RATES

Prior to orthopedic surgeries, it has been common practice to check urinalysis and urine culture prior to surgery and to treat positive results even in the absence of symptoms. This group examined data using this approach versus more recent data collected after protocol was changed to treat only those patients with actual urinary symptoms. In the “pre-practice change period,” 160 of 5340 patients were treated preoperatively for a positive urine culture, although only 40 of these 160 patients were symptomatic. In the “post-practice change period,” 10 of 4609 patients had symptomatic urinary tract infections and received antibiotic treatment. There was no difference in urinary tract infection rates in the 2 groups during the subsequent hospitalization. The authors conclude that routine urinalysis is not necessary prior to elective orthopedic surgery and in this study noted a 93% reduction in antibiotic utilization in the second group.

Comment: The rationale for preoperative urinalysis in asymptomatic patients undergoing orthopedic surgery is fuzzy at best. The pathogens associated with urinary tract infections do not typically lead to wound site infections. This study confirms what many infectious diseases practitioners have long suspected. See also summary of the next presentation.

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2. ORAL ABSTRACTS SESSION 84, THURSDAY OCTOBER 4, 2018. ORAL PRESENTATION 858: GALLEGOS J, OBRIEN W, STRYMISH J, ITANI K, ET AL. PREOPERATIVE “DIRTY” URINALYSIS LEADS TO ANTIBIOTIC USE WITHOUT BENEFIT

This group studied Veterans Affairs patients who had undergone cardiac, orthopedic, or vascular surgery between 2008 and 2013. Of 17,749 preoperative urine samples, 1812 (10.7%) of patients had pyuria-positive, culture-negative results. Of these, 574 (32%) received antibiotics for urinary tract infection. Rates of postoperative wound infections and urinary tract infections were similar in those patients who had received antibiotics compared with those who had not.

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3. POSTER SESSION 64, OCTOBER 4, 2018. POSTER 616: GOLOB J, STOHS E, SWEET A, PERGAM S, ET AL. VANCOMYCIN IS FREQUENTLY ADMINISTERED TO HEMATOPOIETIC CELL TRANSPLANT RECIPIENTS WITHOUT A PROVIDER DOCUMENTED INDICATION AND CORRELATES WITH MICROBIOME DISRUPTION AND ADVERSE EVENTS

The authors studied 70 hospitalized hematopoietic stem cell transplant recipients over time. Fifty-three percent of the patients received intravenous vancomycin. Of those, nearly half were given vancomycin unnecessarily, per guidelines for neutropenic sepsis. The gut microbiome was significantly altered in those receiving vancomycin, including lower concentrations of bacteria that are felt to be protective against graft-versus-host disease and Clostridium difficile.

Comment: This work highlights the relationship of graft-versus-host disease with a disrupted gut microbiome and again points toward the need for vigilant antimicrobial stewardship.

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4. ORAL ABSTRACTS SESSION 215. OCTOBER 6, 2018. ORAL ABSTRACT 1772: CUARESMA E, LASZKOWSKA M, STUMP S, MOSCOSO D, ET AL. VANCOMYCIN-RESISTANT ENTEROCOCCUS ALTERS THE GASTROINTESTINAL MICROBIOME IN CRITICALLY Ill PATIENT

Ninety-seven adults just admitted to the intensive care unit were studied for stool flora. Rectal swabs were obtained at 24 and 72 hours, looking for vancomycin-resistant Enterococcus (VRE), methicillin-resistant Staphylococcus aureus, resistant gram-negatives, and Blautia producta (the latter is considered a component of the healthy intestinal flora). Over the 3-day period, those patients who remained free of VRE had much higher concentrations of B. producta than those who became colonized with VRE.

The authors note that in the murine model direct fecal transplantation of B. producta has been shown to inhibit VRE growth. They speculate that B. producta “may have promise as a probiotic designed to prevent VRE colonization.”

Comment: The composition of commercially available probiotics is not guided by data. This study highlights a possible step toward determining what targeted bacteria may be most helpful in preventing disease.

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5. POSTER SESSION 131, OCTOBER 5, 2018. POSTER 1062: FOX M, ZEQOLLARI K, LEE G, PONTIGGIA L, ET AL. DAPTOMYCIN/CEFTAROLNE IN COMBINATION VERSUS VANCOMYCIN FOR TREATMENT OF METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS (MRSA) BACTEREMIA

Guidelines for the management of persistent MRSA bacteremia state that in the case of vancomycin treatment failure, high-dose daptomycin plus a β-lactam is recommended. In vitro data suggest synergy between daptomycin and ceftaroline by enhancing daptomycin binding to the MRSA cell wall.

This was a retrospective, single-center cohort study. Patients with MRSA bacteremia who received either vancomycin or daptomycin/ceftaroline were matched on a 1:1 basis. Cohort matching was based on source, age, and renal function. The primary end point was time to sterilization of blood cultures. A total of 41 patients were studied. Patients in the daptomycin/ceftaroline group were more likely to have hardware (P = 0.001) and secondary complications.

There was no statistical difference between groups in microbiological cure (P value not given), clinical cure (P = 0.743), mortality (P = 0.729), and MRSA-attributable mortality (0.242). Duration of hospital stay was lower in the vancomycin group (median, 15 vs 29 days, P = 0.018). In conclusion, the combination of daptomycin/ceftaroline appeared to provide no benefit compared with vancomycin monotherapy.

Comment: It has been well established that vancomycin monotherapy is often inadequate for invasive or persistent MRSA infections.1 Daptomycin and ceftaroline have both emerged as “treatments of choice” in cases of vancomycin failure; however, the relationship between vancomycin treatment failure and daptomycin nonsusceptibility in MRSA can be concerning.2 This study was ambitious, but its generalizability is limited. Future studies are needed to more accurately determine the clinical impact of this combination. Daptomcyin in combination with antistaphylococcal β-lactams, such as nafcillin or oxacillin, has also been studied in persistent MRSA bacteremia.3 Because of the cost associated with daptomycin/ceftaroline combination, a study comparing that combination with daptomycin/antistaphylococcal β-lactam or ceftaroline monotherapy would also be valuable in determining the most cost-effective method of dealing with such infections.

  1. Liu C, Bayer A, Cosgrove SE, et. al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis. 2011;52(3):e18.
  2. Van Hal SJ, Paterson DL, Gosbell IB. Emergence of daptomycin resistance following vancomycin-unresponsive Staphylococcus aureus bacteraemia in a daptomycin-naïve patient—a review of the literature. Eur J Clin Microbiol Infect Dis. 2011;30(5):603–610.
  3. Dhand A, Bayer AS, Pogliano J, et. al. Use of antistaphylococcal beta-lactams to increase daptomycin activity in eradicating persistent bacteremia due to methicillin-resistant Staphylococcus aureus: role of enhanced daptomycin binding. Clin Infect Dis. 2011;53(2):158.
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6. POSTER SESSION 145, OCTOBER 5, 2018. POSTER 1385: LODISE T, SMITH N, HOLDEN P, O'DONNELL J, ET AL. EFFICACY OF CEFTAZIDIME-AVIBACTAM IN COMBINATION WITH AZTREONAM (COMBINE): SOLUTIONS FOR METALLO-β-LACTAMASE PRODUCING CARBAPENEM-RESISTANT ENTEROBACTERIACEAE (MBL)

Metallo-β-lactamases (MBLs) are a specific subtype of carbapenemase enzymes that are unaffected by the newer β-lactamases such as avibactam. One novel treatment strategy to overcome this resistance mechanism is combing aztreonam (ATM) with ceftazidime-avibactam (CAZ-AVI). Aztreonam remains stable in the presence of MBLs but is hydrolyzed by other enzymes such as ESBLs and AmpC s. Avibactam provides protection for ATM against the other enzymes, allowing ATM to exert its antimicrobial activity.

This study was performed using a Hollow Fiber Model, which is an in vitro model that mimics human pharmacokinetics and pharmacodynamics. Strains of Escherichia coli and Klebsiella pneumoniae producing the NDM, CTX-M, CMY, TEM, SHV, and DHA β-lactamase enzymes were studied at 7.5 log10 colony-forming units (CFU)/mL. Dosing regimens of CAZ-AVI at 2.5 g every 8 hours and ATM at 2 g every 8 hours (each given as either 2-hour infusion or 24-hour continuous infusion) were simulated. Each antibiotic was administered alone, sequentially in combination, or simultaneously in combination. Growth was measured at 168 hours after initiation. Aztreonam alone mimicked the control group in terms of antimicrobial effect on growth. Ceftazidime–AVI alone showed some intrinsic activity compared with the control group (+3.14 vs +1.19 log10 CFU/mL growth, respectively). The combination given simultaneously as continuous infusions resulted in the most dramatic killing at 50 hours, which was sustained at 168 hours (−5.78 and − 3.90 log10 CFU/mL, respectively). The continuous infusion model was superior to the 2-hour simultaneous infusion model, which was in turn superior to the 2-hour sequential infusion model.

The combination of ATM and CAZ-AVI was shown to be synergistic in the Hollow Fiber Model against MBL-CRE. This provides early evidence for therapeutic regimens against potentially “untreatable” infections.

Comment: Treatment strategies for these potentially untreatable infections are in high demand. Novel antibiotics that are designed to treat such infections will likely not be commercially available until 2021. This forces us as clinicians to get “creative” with combinations of available antibiotics based on in vitro data. The hypothesis tested here, based on specific enzyme affinity against specific antimicrobials, was validated. This early pharmacokinetics/pharmacodynamics study demonstrated that the continuous infusion model was superior to the 2-hour infusion model. This potentially provides researchers with an optimal dosing regimen to examine in future in vivo or human subject studies.

Keywords:

antimicrobial stewardship; ceftazidime-avibactam; metallo-β-lactamase; MRSA bacteremia; preoperative clearance

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