Recent Key Papers Flashcards
Changes to gentamicin in new AHA endocarditis guidelines
Gentamicin is no longer recom- mended by AHA as an optional addi- tion to nafcillin, cefazolin, or vanco- mycin for IE caused by S. aureus in patients with NVE due to evidence of increased nephrotoxicity and no ad- ditional reduction in mortality or the frequency of cardiac complications with gentamicin use.8
Lee eat al Cefepime for Enterobacter bacteremia with S-DD results
new cefepime suscep- tibility category, “susceptible dose- dependent” (SDD), with an associated MIC of 4–8 mg/mL.
clinical outcomes of adult patients with bacteremia due to cefepime-SDD E. cloacae who were treated with cefepime or a carbapen- em relative to outcomes in patients with cefepime-susceptible E. cloacae treated with cefepime.
The 30-day mortality rates were simi- lar in patients empirically treated with cefepime and those treated with a carbapenem (24.5% [13 of 53 pa- tients] versus 25.8% [8 of 31 patients]; p = 1.0).
72 patients who re- ceived definitive cefepime therapy, the 30-day mortality rate of those infected by cefepime-susceptible isolates was significantly lower than that of patients infected by cefepime- SDD isolates (16.1% [9 of 56 patients] versus 62.5% [10 of 16 patients], p < 0.001) but similar to that of 72 patients with definitive carbapenem therapy (16.1% [9 of 56 patients] versus 22.2% [16 of 72 patients], p = 0.50).
Britt daptomycin vs linezolid in VA patients
there were significant baseline differences between patients treated with linezolid versus dapto- mycin indicating greater severity of ill- ness among linezolid-treated patients.
The study authors conclud- ed that daptomycin (median dose, 6 mg/kg/day) offered a significant advantage over linezolid in terms of microbiological clearance (p = 0.011) and 30-day mortality (p = 0.014).
The study authors conclud- ed that daptomycin (median dose, 6 mg/kg/day) offered a significant advantage over linezolid in terms of microbiological clearance (p = 0.011) and 30-day mortality (p = 0.014).
Dulhunty Australia/NZ continuous infusion study
Australia and New Zealand in- tensive care units (ICUs), patients with severe sepsis undergoing treat- ment with piperacillin–tazobactam, ticarcillin–clavulanate, or meropenem were randomly assigned to receive ei- ther intermittent- (over 30 minutes) or continuous-infusion antibiotic ad- ministration.12
primary outcome was “alive ICU-free days” at 28 days after randomization.
no significant between- group difference in the primary out- come of alive ICU-free days at 28 days or in any secondary outcome
a specific pathogenic organism was not isolated in a sub- stantial proportion of patients (81%),
The patients in this study, while critically ill, were primarily infected with highly susceptible organisms, and dosing was relatively aggressive.
Marr et al. Combination antifungal therapy for invasive aspergillosis
randomized, double-blind, placebo-controlled mul- ticenter trial, funded by Pfizer Inc., designed to assess the safety and effi- cacy of voriconazole alone or in com- bination with anidulafungin in the management of IA in patients with HM and HCT recipients at low risk for death due to malignancy or or- gan failure.13 The primary endpoint of the study was all-cause mortality at 6 weeks. Secondary endpoints included all-cause mortality at 12 weeks and 6-week mortality in multiple prespeci- fied subgroupings
either i.v. anid- ulafungin (200 mg on day 1, then 100 mg every 24 hours) or a placebo for at least 2 weeks and up to a maximum of 4 weeks.
mortality at 6 weeks in the mITT pop- ulation was 19.3% (26 of 135 patients) with combination treatment and 27.5% (39 of 142 patients) with mono- therapy (absolute difference, –8.2% [95% confidence interval [CI], –19.0% to 1.5%]; two-sided p = 0.087)
The investigators concluded that treatment of IA with a combination of voriconazole and anidulafungin was associated with a nonsignificant but clinically meaningful survival benefit in patients with HM and HCT recipients.
McDanel et al. Comparative effectiveness of beta- lactams versus vancomycin for treatment of methicillin- susceptible Staphylococcus aureus bloodstream infections among 122 hospitals10
multicenter, retrospective cohort study of medical and surgi- cal patients with MSSA bacteremia, McDanel et al.10 compared (1) em- pirical therapy with vancomycin and b-lactams and (2) definitive therapy with vancomycin and b-lactams. The study was performed at 122 acute care VA medical centers from 2003 to 2010. Patients were included in the analysis
analyses were performed: empirical vancomycin therapy versus empirical b-lactam therapy, definitive vancomycin therapy versus definitive b-lactam therapy, and definitive van- comycin therapy versus definitive guideline-concordant b-lactam ther- apy (cefazolin or an antistaphylococ- cal penicillin).
cefazolin or an antistaphylo- coccal penicillin as definitive therapy had a 43% lower risk of mortality than those who received definitive van- comycin therapy after adjustment for confounders (HR, 0.57; 95% CI, 0.46–0.71)
Paul et al. Trimethoprim- sulfamethoxazole versus vancomycin for severe infections caused by meticillin resistant Staphylococcus aureus: randomised controlled trial16
Paul et al.16 conducted a four-center, randomized, open-label noninferior- ity trial involving patients with severe MRSA infections, including bactere- mia, who received either trimethoprim– sulfamethoxazole (320 mg of trimeth- oprim) twice daily or vancomycin (a starting dose of 1 g daily, with the dos- age adjusted to maintain a trough con- centration between 10 and 20 mg/mL)
patients with left-sided endocarditis were ex- cluded, as were patients with meningi- tis or chronic renal failure and certain neutropenic patients, including bone marrow transplant recipients.
> 1).76 No signifi- cant difference was found in the rates of clinical failure in patients receiv- ing trimethoprim–sulfamethoxazole and those receiving vancomycin (38% and 27%, respectively; risk ratio [RR], 1.38 [95% CI, 0.96–1.99]); however, the lower limit of the 95% CI for the absolute between-group difference (–1.2% to 21.5%) exceeded the pre- specified noninferiority margin
trimethoprim–sulfamethoxazole to vancomycin could not be established. There was no statistical difference in 30-day mortality between the two groups. However, the rate of mortality was nearly doubled in patients receiv- ing trimethoprim–sulfamethoxazole for bacteremia (34% versus 18% with vancomycin use; RR, 1.90 [95% CI, 0.92–3.93]);
In mul- tivariate analysis with adjustment for confounders, treatment with trimethoprim–sulfamethoxazole was a significant risk factor for treatment failure (odds ratio [OR], 2.00; 95% CI, 1.09–3.65).
Rao et al. Treatment outcomes with cefazolin versus oxacillin for deep-seated methicillin- susceptible Staphylococcus aureus bloodstream infections15
Rao et al.15 performed a two- center, retrospective cohort review of outcomes data on adult inpatients with MSSA bacteremia who received more than 48 hours of definitive therapy with either cefazolin or oxa- cillin between January 2010 and April 2013. The primary outcome of interest was treatment failure, defined as (1) a switch in therapy away from cefazo- lin or oxacillin due to clinician docu- mentation of ineffectiveness or (2) in-hospital mortality, with documen- tation of MSSA as the primary inciting factor.
Overall, treatment failure occurred more frequently (but not sig- nificantly so) in the oxacillin-treated group (12.1% versus 5.8%; adjusted OR, 3.76 [95% CI, 0.98–14.4], p = 0.053), while a change in therapy to an alternative agent was significantly more common among oxacillin-treated patients (43.1% versus 20.4%, p = 0.002).
Sawyer et al. Trial of short- course antimicrobial therapy for intraabdominal infection
(STOP-IT), an open- label, randomized, controlled mul- ticenter trial investigating whether the administration of fixed-duration antibiotic therapy for 4 days after ad- equate source control could result in outcomes equivalent to those with the traditional strategy of administra- tion of antibiotics until 2 days after resolution of systemic inflammatory response syndrome, with treatment continued for a maximum of 10 days.
Ad- equate source control was achieved in approximately one third of the pa- tients with percutaneous drainage
Antibiotics were given for 4 days (IQR, 4–5 days) in the experimental group and 8 days (IQR, 5–10 days) in the control group.
No significant difference was found in the primary endpoint, a composite of surgical site infection, recurrent intraabdominal infection, and death within 30 days, in the experimental versus control group (rate of occur- rence, 21.8% versus 22.3%; absolute difference, –0.5 percentage point; 95% CI, –7.0 to 8.0 points; p = 0.92)
no significant between-group difference was demonstrated at the interim analysis, the study was de- funded due to concern for futility, and the enrollment target was not at- tained.
Tamma et al. Carbapenem therapy is associated with improved survival compared with piperacillin-tazobactam for patients with extended- spectrum b-lactamase bacteremia11
Patients initiated on piperacillin–tazobactam whose therapy was subsequently modi- fied to any noncarbapenem regimen were excluded from the analysis, as were patients receiving piperacillin– tazobactam despite documentation of an isolate resistant to piperacillin– tazobactam (defined as a MIC of >16 mg/mL).
the exclusion of over 100 patients who were changed from piperacillin–tazobactam to other therapies (primarily ciprofloxacin and trimethoprim–sulfamethoxazole), indi- cating a patient population who may have been doing well on empirical piperacillin–tazobactam therapy; this exclusion could have resulted in selec- tion bias.
Mortality rates at 14 days were 17% in the piperacillin–tazobactam group and 8% in the carbapenem group (HR, 1.78; 95% CI, 1.00–3.13); in the multivariable analysis, the adjusted HR for mortality with piperacillin– tazobactam use was 1.92.
Lundgren et al., for the INSIGHT START Study Group. Initiation of antiretroviral therapy in early asymptomatic HIV infection28
INSIGHT START Study Group conducted a randomized controlled trial in 35 countries to answer the question of whether early initiation of ART in asymptomatic HIV-infected in- dividuals with high CD4+ counts can provide clinical benefit
of >500 cells/ mm3 were randomly assigned to either immediate or deferred ART initiation until a decline in the CD4+ count to 350 cells/mm3 or development of an AIDS-related condition that dictated the use of ART
the median CD4+ count was 651 cells/mm3 at enrollment. The mean follow-up time was three years. Tenofovir, emtricitabine, and efavirenz were the most commonly prescribed antiretroviral medications
Patients in the immediate- initiation group had a 72% relative re- duction in serious AIDS-related events (p < 0.001), which was mainly due to decreased rates of tuberculosis, Kaposi’s sarcoma, and malignant lymphomas.
Davis et al. Combination of Vancomycin and Beta-Lactam Therapy for Methicillin- Resistant Staphylococcus aureus Bacteremia: A Pilot Multicenter Randomized Controlled Trial
Patients were randomized (1:1) to receive either flucloxacillin 2 g IV every 6 hours for 7 days (combination therapy) or no additional therapy (standard therapy). Vancomycin was adjusted to maintain a mean trough level of 15 mg/L
the mean duration of bacteremia was 1.94 days in the combination therapy group versus 3 days in the standard therapy group. The mean time to resolution of bacter- emia in the combination therapy group was 65% faster than that of the standard therapy group (95% confidence interval [CI]: 41%-102%; P ¼ .06).
more patients in the combination therapy had a rise in serum creati- nine (SCr) of >50% above baseline (28% vs 11%).
Freedberg et al. Receipt of Antibiotics in Hospitalized Patients and Risk for Clostridium Difficile Infection in Subsequent Patients Who Occupy the Same Bed17
a retrospective, multicenter, cohort study to evaluate whether receipt of an antibiotic by previous patients occupying a given hospital bed is associated with an increased risk of CDI in subsequent patients occupying the same bed.
The primary exposure evaluated was receipt of 1 antibiotic by the prior patient, and the primary end point was incident CDI in the subsequent patient occupying the same bed. CDI was defined as a positive polymerase chain reaction (PCR) test result for the C difficile toxin B gene from a diarrheal stool sample and receipt of antibiotics for CDI.
Receipt of antibiotics was the only risk factor related to prior patients that was associated with an increased risk of CDI in subsequent patients (adjusted hazard ratio [aHR]: 1.22; 95% CI: 1.02-1.45) after adjusting for known CDI risk factors in the subsequent patient.
Kalil et al. Management of Adults With Hospital-Acquired and Ventilator-Associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society
shift from disease onset (early vs late) to overall risk factors for MDR pathogens as the determinant of empiric therapy.
Risk factors for MDR VAP include VAP onset 5 days after hospitalization, IV antibiotics within the previous 90 days, septic shock at VAP onset, acute respiratory distress syndrome preceding VAP, and acute renal replacement ther- apy prior to VAP onset.
Empiric dou- ble coverage for VAP is recommended in patients with risk factors for MDR pathogens (discussed above), patients in units where >10% of gram-negative pathogens are resistant to an agent being considered for monotherapy
MacFadden et al. Impact of a Reported Beta-Lactam Allergy on Inpatient Outcomes: A Multicenter Prospective Cohort Study
a prospective cohort study in 3 academic hospitals in North America to evaluate the impact of reported beta-lactam allergy (BLA) and subsequent therapy on patient outcomes
patients without BLA (group 1); patients with BLA but beta-lactam therapy was not preferred (group 2); patients with BLA where beta-lactam therapy was preferred and administered (group 3); and patients with BLA where beta-lactam therapy was preferred but not administered (group 4).
primary outcome was a composite end point of treatment-related adverse events including acute kidney injury (AKI), CDI within 3 months, adverse drug reaction (ADR) requir- ing discontinuation, and readmission for the same infection.1
In univariate analysis, patients in group 4 were more likely than those in group 1 to experience the primary outcome (40% vs 16%; P < .05), which was driven by infection-related readmissions (24% vs 6%; P < .05) and ADRs (8% vs 0.5%; P < .05).
