Merck announces positive trial data for pneumococcal vaccine candidate

News brief
Streptococcus pneumoniae illustration
CDC / Meredith Newlove

Pharmaceutical company Merck last week announced positive topline results from two phase 3 trials of its investigational 21-valent pneumococcal vaccine.

The vaccine, V116, covers the 21 serotypes of Streptococcus pneumoniae that are responsible for 85% of invasive pneumococcal disease in adults ages 65 years and older and includes 8 serotypes that represent adult pneumococcal disease and are not currently covered by pneumococcal vaccines. If approved, it would be the first pneumococcal conjugate vaccine specifically designed for adults.

In the STRIDE-3 trial, V116 demonstrated statistically significant immune responses 30 days post-vaccination when compared with the pneumococcal 20-valent conjugate vaccine (PCV20) in vaccine-naïve adults for serotypes common to both vaccines. In the STRIDE-6 trial, which evaluated the safety, tolerability, and immunogenicity of V116 in adults aged 50 and older who had received pneumococcal vaccination at least one year before enrollment, the vaccine demonstrated immunogenicity for all 21 serotypes. Both studies showed V116 had a safety profile that was comparable to the comparator vaccines (PCV13, PCV15, PCV20, and PPSV23).

Could represent an additional weapon

"Despite the availability of current pneumococcal conjugate vaccines, many adults remain vulnerable to pneumococcal disease, especially those who are older," Eliav Barr, MD, senior vice president, head of global clinical development, and chief medical officer at Merck Research Laboratories, said in a company press release. "These results support the potential for V116 to become an important new preventative option for adults, regardless of prior pneumococcal vaccination status, by expanding coverage to include eight serotypes not currently included in any licensed vaccine."

Despite the availability of current pneumococcal conjugate vaccines, many adults remain vulnerable to pneumococcal disease, especially those who are older.

Merck says it will make the trial results available to the scientific community in the near future. Four other phase 3 trials of V116 are still ongoing.

Sporicidal disinfectants shown more effective against Candida auris

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Candida aurisTesting by a team of researchers with the Louis Stokes Cleveland VA Medical Center indicates that sporicidal disinfectants are more effective against the multidrug-resistant fungal pathogen Candida auris than quaternary-ammonium disinfectants, according to a study published today in Infection Control & Hospital Epidemiology.

For the study, the researchers tested 23 disinfectants used for cleaning and disinfecting surfaces at 57 healthcare facilities in 30 states. The products included chlorine- and peracetic acid–based disinfectants, which are sporicidal, and quaternary-ammonium and hydrogen peroxide–based disinfectants, which are not. To test their efficacy against C auris, the researchers used a three-part soil load containing isolates from four phylogenetic clades of C auris—including the drug-resistant clade 4 strain AR-0385—and a strain of Candida albicans and then cultured the soiled surfaces after they were treated.

The disinfectants were classified as effective if a greater than 5 log10 reduction in C auris was achieved.

Cleaning and disinfection practices may not be sufficient to limit spread.

Overall, five chlorine-based disinfectants and the one peracetic acid–based disinfectant consistently reduced all the C auris and C albicans strains by 5 log10 or more, as did three hydrogen peroxide–based cleaners. But the quaternary-ammonium disinfectants were largely ineffective. Only one product reduced C auris strains by more than 5 log10, but it wasn't effective against the drug-resistant AR-0385 strain.

Current practices may not cut it

The study authors say that while real-world studies are needed, the findings are important because quaternary-ammonium disinfectants are widely used in US healthcare facilities, which have seen a dramatic increase C auris colonization and infection in recent years.

"The fact that many patients with C. auris are colonized and only detected through screening increases the likelihood that unrecognized cases may enter facilities where cleaning and disinfection practices may not be sufficient to limit spread," they wrote.

Single-center study finds no reduction in antibiotic use with stool PCR tests

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Use of a rapid polymerase chain reaction (PCR) test in patients with infectious diarrhea did not reduce antibiotic use compared with stool culture, researchers reported today in Antimicrobial Stewardship & Healthcare Epidemiology.

To evaluate the impact of multiplex stool PCR testing versus stool culture on antibiotic use in patients with infectious diarrhea, researchers from Baylor College of Medicine evaluated data on hospitalized adult patients with suspected infectious diarrhea during two periods: the preintervention period, when stool cultures were routinely collected from patients, and the postintervention period, when all orders for stool cultures were converted in the electronic health record (EHR) to multiplex stool PCR tests. The primary outcomes included antibiotic days of therapy (DOT) and length of therapy (LOT).

In the preintervention group, stool cultures were negative in 71 (94.7%) of 75 patients, compared with negative stool PCR panels in 58 (71.6%) of 81 patients in the postintervention group. There was no meaningful difference in DOT and LOT between the two groups. In both groups, the median DOT and LOT were 0 days, with ranges of 0 to 10 days (DOT) and 0 to 5 days (LOT) in the preintervention group and 0 to 8 and 0 to 5 days in the postintervention group. Similarly, the incidence rate ratios for DOT (0.71; 95% confidence interval [CI], 0.42 to 1.22) and LOT (0.67; 95% CI, 0.36 to 1.24) indicated no change in the incidence rate after the intervention.

Findings might not be generalizable

The study authors note that other research on multiplex stool PCR tests, which have much faster turnaround times than stool cultures, has produced different outcomes, and that the small sample size of the study, and their institution's existing culture of antimicrobial stewardship, could diminish the generalizability of the findings.

"Future research investigating the impact of stool PCR testing on antimicrobial use may help inform clinical decision making or the development of clinical decision-support tools within EHRs," they wrote. "As antibiotic stewardship becomes increasingly essential with the advent of drug-resistant pathogens, diagnostic stewardship must be considered in patient evaluation and treatment, including the turnaround time and result sensitivity."

Diagnostic stewardship must be considered in patient evaluation and treatment.

Risk of severe flu outcomes 7-fold higher in poorer nations, analysis finds

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Empty ICU bedThe risk of flu-related intensive care unit (ICU) admission was sevenfold higher in lower middle-income countries (LMICs) than in high-income countries (HICs), according to an analysis yesterday in the Journal of Infectious Diseases.

The Global Influenza Hospital Surveillance Network conducted the study, the first to evaluate years of global, patient-level data from hospitals to determine geographic differences in flu severity. The analysis included 15,660 patients admitted to 116 hospitals in 22 countries for flu from 2012 through 2019. Of all patients, 72.4% had influenza A, and 27.6% had influenza B.

"Given lack of routine testing for influenza, and the complex pathway by which influenza can exacerbate chronic conditions and lead to severe disease, influenza burden estimates remain uncertain, especially in data-poor settings," the authors wrote.

Comorbidities doubled the risk

After adjustment for patient-level covariates, the risk of flu-related ICU admission was sevenfold higher in LMICs than in HICs. Having two or more underlying medical conditions significantly heightened the likelihood of ICU admission, mechanical ventilation, and in-hospital death (adjusted odds ratios [aORs], 2.40, 2.58, and 1.66, respectively), while female sex was protective against death (aOR, 0.80).

Relative to patients aged 5 to 64 years, those 65 and older had double the odds of death (aOR, 2.18), and those younger than 5 had lower chances of ICU admission, mechanical ventilation, and death (aORs, 0.67, 0.67, and 0.17, respectively).

Delayed care-seeking in LMIC could contribute to the increased severity.

Admission during the 2017-18 flu season increased the risk of ICU admission, mechanical ventilation, and death (aORs, 1.62, 2.15, and 1.37, respectively). Infection with the influenza A H1N1 strain independently predicted ICU admission (aOR, 1.67), mechanical ventilation (aOR, 1.47), and death (aOR, 1.37) compared with influenza A H3N2.

The researchers noted that flu vaccination is generally less available in LMICs. "Moreover, differences in standards of care and/or lack of access to antivirals in LMIC are also a possible explanation," they wrote. "Delayed care-seeking in LMIC could contribute to the increased severity."

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