Journal Club
In this feature, a panel of IDSA members identifies and critiques important new studies in the current literature that have a significant impact on the practice of infectious diseases medicine.
- The Impact of an Anti-staphylococcal β-Lactam in Patients with MRSA Bacteremia
- Chronic Antimicrobial Therapy for Periprosthetic Joint Infection with Implant Retention: Is Longer Better?
- Antiretroviral Therapy and Neurocognitive Outcomes
- When to Draw Blood Cultures? A Culture Change May be Needed
Did you miss the previous edition of Journal Club? You can find it and other past installments in the IDSA News archives. For a review of other recent research in the infectious diseases literature, see “In the Literature,” by Stanley Deresinski, M.D., FIDSA, in each issue of Clinical Infectious Diseases.
The Impact of an Anti-staphylococcal β-Lactam in Patients with MRSA Bacteremia
Reviewed by Terri Stillwell, M.D.
Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia continues to cause significant morbidity and mortality, leaving clinicians searching for alternative treatments to optimize patient care. Previous studies have indicated that the addition of an anti-staphylococcal β-lactam could improve overall outcomes. In a recent study in JAMA, the authors assessed whether adding a β-lactam to standard treatment improves outcomes in adult patients with MRSA bacteremia.
In this trial, patients were randomized to either standard treatment (with vancomycin or daptomycin at the clinician’s discretion) or combination treatment, which involved standard treatment plus an anti-staphylococcal β-lactam (flucloxacillin or cloxacillin) for 7 days following randomization. The primary outcome was a composite end point, including mortality, persistence of bacteremia, microbiologic relapse, and treatment failure.
Three hundred fifty-six patients were randomized, with 174 receiving combination therapy. There was no difference in the composite primary outcome between the two treatment groups (P = .42). When analyzing secondary outcomes, persistent bacteremia at day 5 was significantly less in those receiving combination therapy (difference, -8.9%; 95% confidence interval [CI], -16.6% to 1.2%). However, there was no difference between treatment groups with regards to mortality. Additionally, acute kidney injury (AKI) was significantly increased in the combination treatment group, such that the study was stopped early due to this safety concern (difference, 17.2%; 95% CI, 9.3% to 25.2%).
Given these findings, the authors concluded that the addition of an anti-staphylococcal β-lactam did not improve overall patient outcomes, as indicated by the primary composite end point and, in fact, created additional risk for AKI. That being said, the study was discontinued early and therefore may have been underpowered to detect an impact, and the use of an anti-staphylococcal cephalosporin (which has decreased risk of AKI) may provide different results. Additional studies are warranted.
(Tong et al. JAMA. 2020;323(6):527-537.)
Chronic Antimicrobial Therapy for Periprosthetic Joint Infection with Implant Retention: Is Longer Better?
Reviewed by Jennifer Brown, M.D.
Periprosthetic joint infection (PJI) is a serious complication of total knee arthroplasty (TKA), and its management can be challenging. For patients who cannot undergo a two-stage exchange, debridement, antimicrobial therapy, and implant retention of prosthesis (DAIR) may be employed along with antimicrobial therapy—often intravenous followed by oral antimicrobials for an indefinite duration. Data is limited with respect to failure rates, adverse events, and optimal treatment duration with this approach.
In the Feb. 15 issue of Clinical Infectious Diseases, Shah et al reported the results of their observational study that compared patients with TKA PJI who did, and did not, receive extended antimicrobial therapy following DAIR. Overall, 108 patients were included, with a mean duration of follow-up of 2.3 years. One-third of patients had acute PJI (PJI within 90 days of TKA). Of the PJI, 52% were staphylococcal (58% methicillin-susceptible Staphylococcus aureus and 13% coagulase negative staphylococcus), 24% culture negative, 10% gram-negative, and 8% streptococcal. Fifty-seven (53%) patients received primary antimicrobial therapy ( < 6 weeks), and 51 (47%) received chronic antimicrobial therapy ( > 6 weeks).
Overall, 68.5% of patients who did not and 39.4% who did receive chronic antimicrobial therapy had treatment failure (PJI any time after the primary antimicrobial therapy period) (hazard ratio, 2.47; P = .009). The hazard of failure decreased about 3.8% for each month of antimicrobial therapy regardless of total duration, but at about one year of therapy, significant differences were not observed between patients who received more or less than 12 months of therapy (P = .23). Rates of adverse events did not significantly differ between patients who received > 6 weeks vs < 6 weeks of antimicrobials.
Limitations of the study include its retrospective design and small size. Nonetheless, this study may provide some guidance for the treatment of these difficult infections.
(Shah et al. Clin Infect Dis. 2020;70(4):559-65.)
Antiretroviral Therapy and Neurocognitive Outcomes
Reviewed by Lauren Richey, M.D., MPH, FIDSA
HIV-associated neurocognitive disorder (HAND) is a spectrum of neurocognitive impairment believed to be related to HIV damaging neurons in the brain and leading to dysfunction. The authors of a recent article in AIDS sought to clarify the relationship between antiretroviral therapy (ART), comorbidities, and neurocognitive impairment using a longitudinal retrospective study of over 47,000 patients. These patients were diagnosed from 2009-2013, and ART-naïve and ART-treated patients were the primary comparison. Patients with illicit drug use were excluded. Data came from an insurance database, so patients were insured for at least 20 days prior to their HIV diagnosis to be included. The primary outcome was neurocognitive impairment, defined as HAND, Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, and other dementias not caused by genetic disorders.
The majority of the patients were on ART (64%), were men (75%), and had comorbidities (84%); median age was 45. Median follow-up was 2.8 years. Any neurocognitive impairment was seen in 7.2% of the patients not treated with ART and 3.7% of the treated patients. Using a weighting model, the rate was 24.1 versus 9.4 per 1,000-person-years for untreated and treated, respectively. The proportional hazard model showed that ART significantly reduced the risk of neurocognitive impairment (hazard ratio [HR] 0.41, 95% confidence interval [CI] 0.37-0.45). For HAND, the rates were 7.0 versus 2.3 per 1,000 person-years for untreated and treated, respectively. ART also significantly reduced the risk of neurocognitive impairment (HR 0.51, 95% CI 0.38 to 0.68).
Limitations included the patient population studied, which excluded uninsured patients and patients using illicit drugs. The sample also did not represent many people living with HIV. Additionally, neurocognitive impairment may be underreported as billing codes were used, and these disorders may be underdiagnosed due to not being evaluated or lack of access to neurocognitive testing. Further study into which comorbidities and ART regimens have the largest impact on neurocognitive impairment are still needed.
(Siangphoe et al. AIDS. Published online: Feb. 5, 2020.)
When to Draw Blood Cultures? A Culture Change May be Needed
Reviewed by Manie Beheshti, M.D.
When and why do we order blood cultures? While the answer may seem intuitive, there is limited data to help guide specific practice. Citing this gap in knowledge, a recent study in Clinical Infectious Diseases reports the results of a scoping review of the literature assessing the utility and yield of blood cultures, aiming to summarize the data and to develop a clinical decision tool.
After screening nearly 2,900 studies spanning over 15 years of publication, 51 studies of adult non-neutropenic hospitalized patients met final inclusion criteria. Two categories of studies were defined: those addressing blood cultures sent as part of an initial clinical evaluation of an infectious syndrome and those addressing follow-up blood cultures to document clearance.
Utilizing studies reporting the incidence of bacteremia, selected infectious syndromes could be categorized based on degrees of pretest probability of bacteremia. The authors found that the low incidence of bacteremia, the lack of additional information provided by blood cultures, and the low impact on clinical decision-making (less than 2% in most instances) were sufficient reasons to advise against routine blood cultures in certain clinical syndromes (non-severe community-acquired pneumonia, health care-associated pneumonia, cystitis, prostatitis, and fever in the first 48 postoperative hours). Data supported blood cultures for syndromes with a high pretest probability of bacteremia. The authors also recommended that blood cultures be considered if the primary site of infection cannot be accessed for culture prior to initiation of antibiotics.
Given the proclivity of S. aureus to cause persistent bacteremia, follow-up blood cultures to document clearance were found to be of value, as was the case for the similarly virulent S. lugdunensis. Unless there was an endovascular infection or lack of source control, follow-up blood cultures in streptococcal and most gram-negative infections were low yield and advised against.
Although this study was limited to observational studies and immunosuppressed patients were not well represented, it provides the best available data addressing one of the most common questions: When to order blood cultures? The authors astutely developed an algorithm providing the first evidence-based blueprint that may prompt a change in blood culture ordering. Further validation and analysis of this algorithm in clinical practice would be of great interest.
(Fabre et al. Clin Infect Dis. Published online: Jan. 14, 2020.)