Streptococcus pneumoniae inflicts a huge disease burden as the leading cause of community-acquired pneumonia and meningitis. Soon after mainstream antibiotic usage, multiresistant pneumococcal clones emerged and disseminated worldwide. Resistant clones are generated through adaptation to antibiotic pressures imposed while naturally residing within the human upper respiratory tract. Here, a huge array of related commensal streptococcal strains transfers core genomic and accessory resistance determinants to the highly transformable pneumococcus. β-Lactam resistance is the hallmark of pneumococcal adaptability, requiring multiple independent recombination events that are traceable to nonpneumococcal origins and stably perpetuated in multiresistant clonal complexes. Pneumococcal strains with elevated MICs of β-lactams are most often resistant to additional antibiotics. Basic underlying mechanisms of most pneumococcal resistances have been identified, although new insights that increase our understanding are continually provided. Although all pneumococcal infections can be successfully treated with antibiotics, the available choices are limited for some strains. Invasive pneumococcal disease data compiled during 1998 to 2013 through the population-based Active Bacterial Core surveillance program (U.S. population base of 30,600,000) demonstrate that targeting prevalent capsular serotypes with conjugate vaccines (7-valent and 13-valent vaccines implemented in 2000 and 2010, respectively) is extremely effective in reducing resistant infections. Nonetheless, resistant non-vaccine-serotype clones continue to emerge and expand.

Biological and Epidemiological Features of Antibiotic-Resistant Streptococcus pneumoniae in Pre- and Post-Conjugate Vaccine Eras: a United States Perspective

Introduction: The aim is to quantify community-acquired pneumonia (CAP) treatment outcomes and costs from a managed care perspective by the level of macrolide resistance corresponding to the metropolitan statistical area (MSA) where patients lived. Materials and methods: A retrospective analysis was conducted using the i3 Magnify database (05/ 2000–05/2005) and the Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin (PROTEKT) database. Continuously enrolled patients aged 18 years and older residing in MSAs with PROTEKT data that had an outpatient CAP-related ICD-9 code and with one antibiotic pharmacy claim within 7 days were included. Patients were excluded for having a prior condition or drug treatment that could mimic CAP or precipitate infections, or for recent hospitalizations. Treatment costs by the level of resistance in the patient’s MSA, by treatment outcome and by initial treatment were measured and adjusted for differences in baseline patient characteristics. Results: The final study included 9446 CAP cases (average age of 47.6 years, 52.2% male). The majority (56.1%) resided in an MSA with macrolide resistance rates of <25%. Treatment success rates were 82.5% and 80.5% for MSAs with resistance levels being <25% and � 25%, respectively (P < 0.001). Treatment failure resulting in hospitalization was higher in resistance areas � 25% at 13.1% versus 8.0% in areas with resistance <25% (P < 0.001). Average adjusted treatment costs were 33% higher for those treated in areas with resistance levels � 25% than for those treated in areas where resistance was <25%. Treatment success was associated with average adjusted costs that were 58% less than those whose initial treatment failed, controlling for level resistance (P < 0.001). Conclusions: This study observed an association between community-level macrolide resistance and treatment and economic outcomes. Treatment failure costs were higher for CAP patients treated in areas with macrolide resistance rates � 25% than for those treated in areas where resistance was � 25%.

/pdf/treatment-costs-associated-with-community-acquired-pneumonia-8l7tunepme.pdf

Treatment costs associated with community-acquired pneumonia by community level of antimicrobial resistance.

Antibiotics are essential to the treatment of bacterial sepsis as they reduce the bacterial burden. The impact of bacterial resistance has recently been studied and found to be important in a range of conditions. Resistance to antibiotics can be defined genotypically, phenotypically and clinically through pharmacokinetic/pharmacodynamic studies and their correlations with clinical outcomes. Although the kinetics of antibiotics has been shown to be favourably altered in sepsis, a range of studies in sepsis has revealed that for most pathogens resistance contributes to significant increases in mortality. This has been clearly demonstrated in bacteraemia, including community- and hospital-acquired infection, and with bacteraemia caused by vancomycin-resistant enterococci, methicillin-resistant staphylococci and extended-spectrum producing Gram-negative bacteria. Significant mortality increases have also been seen with ventilator-associated pneumonia and serious infections requiring admission to intensive care. Gentotypic and phenotypic resistance in coagulase-negative staphylococci causing bacteraemia, and in invasive pneumococcal disease has not shown differences in mortality. In the latter case, dosage regimens have to date been adequate to overcome laboratory-defined resistance. Early indications are that de-escalating therapy from broad-spectrum initial coverage after results of cultures and susceptibility tests become available does not jeopardize outcomes, and further prospective studies are warranted. There is now convincing evidence that broad-spectrum initial therapy to cover the likely pathogens and their resistances pending culture results is mandatory in sepsis to minimize adverse outcomes.

Impact of Antibiotic Resistance on the Treatment of Sepsis

Resource Utilization of Adults Admitted to a Large Urban Hospital With Community-Acquired Pneumonia Caused by Streptococcus pneumoniae

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1524-4733.2008.00410.x

Potential for cost-savings in the care of hospitalized low-risk community-acquired pneumonia patients in China.

Despite failure to correlate in vitro susceptibility with clinical outcomes for respiratory tract infections and bacteremia, resistance affects management of patients with pneumococcal infections. The economic impact of resistance among pneumococci has not been evaluated. We conducted a single-center, retrospective, observational, cohort study of hospitalized patients infected with Streptococcus pneumoniae isolated from blood or a respiratory source between January 1, 1995, and December 31, 1998. Data were collected for 36 days surrounding the day that the first positive culture was collected. Patients were grouped according to isolate penicillin-susceptibility profile [susceptible minimum inhibitory concentration (MIC) ≤ 0.06 μg/ml, nonsusceptible MIC ≥ 0.125 μg/ml), and data were analyzed with respect to health care resource utilization patterns. Of 231 patients identified, 142 and 89 had susceptible and nonsusceptible isolates, respectively. Groups were similar with respect to demographics and comorbidities, except that patients infected with a nonsusceptible isolate were more likely to have the isolate obtained from a respiratory source and to have a history of recent antibiotic therapy. No difference was noted with respect to clinical outcome; however, patients infected with a nonsusceptible isolate had a longer median stay (14 vs 10 days, p<0.05). They also had significantly higher total median costs ($1600, 95% confidence interval $257-2943) due to room and nursing services. Infections caused by penicillin-nonsusceptible pneumococci were not associated with a worse outcome in hospitalized patients but were associated with increased cost of care.

Health Care Resource Utilization Associated with Treatment of Penicillin-Susceptible and -Nonsusceptible Isolates of Streptococcus pneumoniae

Due to geographic isolation and border controls, Aotearoa New Zealand attained high levels of population coronavirus disease-19 (COVID-19) vaccination before widespread community transmission of Omicron variant COVID-19 in early 2022. This provides a unique opportunity to examine outcomes in people with rheumatic diseases immunologically naive to COVID-19.This study aims to describe the outcomes of Omicron variant COVID-19 infection in people with rheumatic diseases in Aotearoa New Zealand.We conducted an observational study of people with inflammatory rheumatic disease and COVID-19 infection from centers in Aotearoa New Zealand between 1 February to 30 April 2022. Data were collected via the Global Rheumatology Alliance Registry, including demographic and rheumatic disease characteristics and COVID-19 vaccination and outcomes. Multivariable logistic regression was used to explore associations of demographic and clinical factors with COVID-19 hospitalisation and death.A total of 1599 cases were included, with 98% from three hospitals that systematically identified all patients from rheumatology clinics who had COVID-19 infection. At the time of COVID-19 infection, 1513 cases (94.6%) had received at least two COVID-19 vaccinations. Hospitalisation occurred for 104 (6.5%) cases, and 10 (0.6%) patients died. A lower frequency of hospitalisation was seen in cases who had received at least two vaccinations (5.9%), compared to cases who were unvaccinated (20.6%) or who received a single vaccine dose (10.7%). In multivariable adjusted models, people with gout (OR 2.2 95% CI 1.02, 4.77) or connective tissue diseases (CTD) (OR 2.78 CI 1.61, 4.80) had increased risk of the combined outcome of hospitalisation and death, compared to people with inflammatory arthritis. Glucocorticoid and rituximab use were associated with 3 to 6 times higher odds of hospitalization and/or death. All cases who died had three or more co-morbidities associated with a known higher risk of poor outcomes or were over 60 years old.In this cohort of people with inflammatory rheumatic diseases with high vaccination rates, severe outcomes from Omicron variant COVID-19 were infrequent. The hospitalisation rate during COVID-19 infection was higher in people who had not completed the primary vaccination course, had gout or CTD, and used glucocorticoids. These findings suggest that outcomes of Omicron variant COVID-19 infection among people with rheumatic disease who are vaccinated but immunologically naive to prior COVID-19 variant infections were favorable.There was no specific funding for data collection. Data analysis was funded by the COVID-19 Global Rheumatology Alliance. The Global Rheumatology Alliance registries are supported by the American College of Rheumatology and European Alliance of Associations of Rheumatology but the views expressed here are of the authors.We thank our colleagues who entered patients to the cohort who include Ms J Heslett, Dr S Bourke, Dr E Chan, Dr S Jordan, Dr K Lindsay, Dr R Murdoch and Dr S Stebbings,Jonathon Brooks: None declared, Anna Montgomery: None declared, Nicola Dalbeth Consultant of: Personal fees from AstraZeneca, Dyve Biosciences, Horizon, Selecta, Arthrosi, JW Pharmaceutical Corporation, PK Med, LG Chem, JPI, PTC Therapeutics, Protalix, Unlocked Labs, Hikma, all outside this abstract, Mark Sapsford: None declared, Amy Cooper: None declared, Rachel Ngan Kee: None declared, Vicki Quincey: None declared, Jean Liew Grant/research support from: Pfizer, outside this abstract, Suleman Bhana Shareholder of: Owns restricted stock units with Pfizer as a Pfizer employee, Consultant of: Honoraria from AbbVie, Horizon, Novartis, Pfizer, has received travel support from Pfizer, Employee of: Pfizer Inc, Monique Gore-Massy Consultant of: Patient consultant for Aurinia Pharmaceuticals, Boehringer Ingelheim, Johnson & Johnson, Bristol-Myers Squibb, all unrelated to this abstract. Receives honoraria from Aurinia Pharmaceuticals, Boehringer Ingelheim, Bristol-Myers Squibb, all unrelated to this abstract, Jonathan Hausmann Consultant of: Consulting fees from Novartis, Pfizer, Sobi and Biogen, all unrelated to this manuscript, Pedro Machado Speakers bureau: PMM has received consulting/speaker’s fees from Abbvie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB, all unrelated to this manuscript, Paul Sufka: None declared, Emily Sirotich: None declared, Philip Robinson Speakers bureau: PR reports personal fees from Abbvie, Atom Biosciences, Eli Lilly, Gilead, GlaxoSmithKline, Janssen, Kukdong, Novartis, UCB, Roche, Pfizer;, Grant/research support from: Meeting attendance support from BMS, Pfizer and UCB and grant funding from Janssen, Novartis, Pfizer and UCB Pharma., Zachary Wallace Consultant of: Consulting fees from Zenas Biopharma, Horizon, Sanofi, Shionogi, Viela Bio, and MedPace, all outside this abstract., Grant/research support from: Research support from Bristol-Myers Squibb and Principia/Sanofi, all outside this abstract., Jinoos Yazdany Consultant of: Consulting fees from Astra Zeneca, Aurinia, Pfizer, all unrelated to this manuscript, Grant/research support from: Grants from Gilead, Astra Zeneca, BMS Foundation, all unrelated to this manuscript, Rebecca Grainger Speakers bureau: RG reports personal fees from AbbVie, Janssen, Cornerstones, Novartis; meeting attendance support from Pfizer.

/pdf/op0079-omicron-variant-infection-in-inflammatory-95mwddsr.pdf

Op0079 omicron variant infection in inflammatory rheumatological conditions - outcomes from a covid-19 naive population in aotearoa new zealand

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Health Care Resource Utilization Associated with Treatment of Penicillin-Susceptible and -Nonsusceptible Isolates of Streptococcus pneumoniae

Op0079 omicron variant infection in inflammatory rheumatological conditions - outcomes from a covid-19 naive population in aotearoa new zealand