Playing “Whack-a-Mole” With Pneumococcal Serotype Eradication

Swanson, Douglas; Harrison, Christopher J.

doi:10.1542/peds.2017-2034

Cited by 4 publications

(1 citation statement)

References 26 publications

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“…Even with improved vaccination rates, however, pneumococcal disease caused by resistant S. pneumoniae is unlikely to disappear. Despite overall reduction in cases caused by AMR S. pneumoniae , wider adoption of pneumococcal vaccination, particularly in children, has been associated with the emergence of drug-resistant serotypes not covered by the vaccine [ 48 , 49 ], leading some experts to liken attempts to eradicate key pneumococcal serotypes to a “whack a mole” game [ 50 ]. Other important components in combatting AMR include antimicrobial stewardship efforts and the development of new drugs that effective against antibiotic-resistant S. pneumoniae [ 4 , 51 ].…”

Section: Discussionmentioning

confidence: 99%

A Multicenter Evaluation of Trends in Antimicrobial Resistance Among Streptococcus pneumoniae Isolates From Adults in the United States

Mohanty

Johnson

Watts

et al. 2022

Open Forum Infectious Diseases

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Background Management of pneumococcal disease is complicated by high rates of antimicrobial resistance (AMR). This study assessed AMR trends for Streptococcus pneumoniae isolates from adults with pneumococcal disease. Methods From January 2011 to February 2020, we evaluated 30-day non-duplicate S. pneumoniae isolates from 290 US hospitals (BD Insights Research Database) from adults (≥ 18 years) in inpatient and outpatient settings. Isolates were required to have at least one AMR result for invasive (blood, cerebrospinal fluid/neurologic) or non-invasive (respiratory or ear/nose/throat) pneumococcal disease samples. Determination of AMR was based on facility reports of intermediate or resistant. Descriptive statistics and generalized estimated equations were used to assess variations over time. Results Over the study period, 34,039 S. pneumoniae isolates were analyzed (20,749 [61%] from non-invasive sources and 13,290 [39%] from invasive sources). Almost half (46.6%) of the isolates were resistant to ≥ 1 drug and non-invasive isolates had higher rates of AMR than invasive isolates. Total S. pneumoniae isolates had high rates of resistance to macrolides (37.7%), penicillin (22.1%), and tetracyclines (16.1%). Multivariate modeling identified a significant increasing trend in resistance to macrolides (+1.8%/year; P < 0.001). Significant decreasing trends were observed for penicillin (-1.6%/year; P < 0.001), extended-spectrum cephalosporins (ESCs) (-0.35%/year; P < 0.001), and ≥3 drugs (-0.5%/year; P < 0.001). Conclusions Despite decreasing trends for penicillin, ESCs, and resistance to ≥3 drugs, AMR rates are persistently high in S. pneumoniae isolates among US adults. Increasing macrolide resistance suggests that efforts to address AMR in S. pneumoniae may require antimicrobial stewardship efforts and higher-valent pneumococcal conjugate vaccines.

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Section: Discussionmentioning

confidence: 99%

A Multicenter Evaluation of Trends in Antimicrobial Resistance Among Streptococcus pneumoniae Isolates From Adults in the United States

Mohanty

Johnson

Watts

et al. 2022

Open Forum Infectious Diseases

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Impact of pneumococcal conjugate vaccines on hospitalizations for pneumonia in the United States

Wiese

Griffin

Grijalva

2019

Expert Review of Vaccines

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Introduction: Pneumonia is one of the leading causes of morbidity and mortality among children and older adults. Pneumococcal conjugate vaccines (PCVs) were introduced into the US routine infant vaccination schedule leading to substantial reductions of invasive pneumococcal diseases (IPD). PCVs introduction also led to reductions in all-cause pneumonia among US children, though the indirect impact of PCVs on pneumonia in adults is difficult to quantify, especially due to the recent US recommendation for direct PCV use in older adults. Areas covered: We described the existing evidence for both the direct and indirect impact of PCVs on pneumonia among children and adults in the US since PCV introduction. Expert opinion: The introduction of PCVs into the US routine infant vaccination schedule led to important reductions in the burden of IPD and non-invasive pneumonia among vaccinated and unvaccinated subjects. The impact of direct vaccination of older adults in the US since 2014, though difficult to quantify, is currently being evaluated. As pneumonia remains one of the leading causes of morbidity and mortality in the US, future evaluations of the direct and indirect effects of current and expanded valency PCVs in the US population are needed.

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Mitigating alemtuzumab-associated autoimmunity in MS

Meltzer

Campbell

Ehrenfeld

et al. 2020

Neurol Neuroimmunol Neuroinflamm

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ObjectiveTo determine whether the punctuated administration of low-dose rituximab, temporally linked to B-cell hyperrepopulation (defined when the return of CD19+ B cells approximates 40%–50% of baseline levels as measured before alemtuzumab treatment inception), can mitigate alemtuzumab-associated secondary autoimmunity.MethodsIn this hypothesis-driven pilot study, 10 patients received low-dose rituximab (50–150 mg/m2), a chimeric anti-CD20 monoclonal antibody, after either their first or second cycles of alemtuzumab. These patients were then routinely assessed for the development of autoimmune disorders and safety signals related to the use of dual monoclonal antibody therapy.ResultsFive patients received at least 1 IV infusion of low-dose rituximab, following alemtuzumab therapy, with a mean follow-up of 41 months. None of the 5 patients developed secondary autoimmune disorders. An additional 5 patients with follow-up over less than 24 months received at least 1 infusion of low-dose rituximab treatment following alemtuzumab treatment. No secondary autoimmune diseases were observed.ConclusionsAn anti-CD20 “whack-a-mole” B-cell depletion strategy may serve to mitigate alemtuzumab-associated secondary autoimmunity in MS by reducing the imbalance in B- and T-cell regulatory networks during immune reconstitution. We believe that these observations warrant further investigation.Classification of evidenceThis study provides Class IV evidence that for people with MS, low-dose rituximab following alemtuzumab treatment decreases the risk of alemtuzumab-associated secondary autoimmune diseases.

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Playing “Whack-a-Mole” With Pneumococcal Serotype Eradication

Cited by 4 publications

References 26 publications

A Multicenter Evaluation of Trends in Antimicrobial Resistance Among Streptococcus pneumoniae Isolates From Adults in the United States

A Multicenter Evaluation of Trends in Antimicrobial Resistance Among Streptococcus pneumoniae Isolates From Adults in the United States

Impact of pneumococcal conjugate vaccines on hospitalizations for pneumonia in the United States

Mitigating alemtuzumab-associated autoimmunity in MS

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