C difficile spores

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Clostridioides difficile infection (CDI) poses significant mortality risks and healthcare burdens. The phase 3 CLOVER trial assessed the detoxified toxin-A/B PF-06425090 vaccine for preventing CDI. Although the vaccine did not meet the primary endpoint of preventing CDI, it was found to be safe and well-tolerated, showing potential in reducing CDI symptom duration, medical attention needs, and antibiotic use.

In the study, 17 recipients of PF-06425090 and 25 placebo recipients experienced their first CDI episode 14 or more days after the third dose, resulting in a vaccine efficacy (VE) of 31% (96.4% CI: –38.7% to 66.6%). For the second dose, 24 PF-06425090 and 34 placebo recipients had their first CDI episode 14 or more days later, with a VE of 28.6% (96.4% CI: –28.4% to 61%). Although, the median duration of CDI was shorter with PF-06425090 (1 day) compared to placebo (4 days; P=.02).¹

The primary endpoints were the incidence of the first CDI episode occurring 14 or more days after the third dose (PD3) and the second dose (PD2). The study also evaluated CDI duration, the need for medical attention, and antibiotic use, along with the vaccine’s tolerability and safety.¹

Among participants with a first CDI episode, no PF-06425090 and 11 placebo recipients sought medical attention, indicating a post hoc estimated VE of 100% (95% CI: 59.6% to 100%). Similarly, no PF-06425090 and 10 placebo recipients required antibiotics, suggesting a VE of 100% (95% CI: 54.8% to 100%). Local reactions were more common with PF-06425090, but systemic events were similar between groups, with most being mild to moderate. Adverse event rates were comparable.¹

This Phase 3 observer-blinded study randomized 17,535 participants aged 50 and older, at increased risk for CDI, to receive either three doses of PF-06425090 or a placebo (administered at 0, 1, and 6 months).¹

This study follows a previous report from Contagion in 2022, where Pfizer announced that its investigational CDI vaccine, PF-06425090, did not meet the primary endpoint of preventing C difficile in the Phase 3 CLOVER trial. Although, vaccine efficacy for all CDI cases recorded 14 days post-dose 3 was 49%, 47%, and 31% at 12 and 24 months, respectively.²

In that report, the vaccine significantly reduced the duration of CDI episodes, with median duration dropping from 4 days to 1 day and mean duration from 16 days to 3 days. In the vaccine group, no participants required medical attention, compared to 11 out of 25 in the placebo group The trial involved approximately 17,500 adults aged 50 and older, randomized to receive either three doses of the vaccine or a placebo. Despite not meeting primary efficacy endpoints, the vaccine was well-tolerated and demonstrated a favorable safety profile. Some secondary endpoints remained unreported.²

Both studies indicate that while the PF-06425090 vaccine did not meet its primary endpoint, it reduced CDI duration and medical interventions. The vaccine was well-tolerated in both studies. Pfizer plans to evaluate the next steps in coordination with regulatory agencies.

References

1. Donskey C, Dubberke E, Klein N, et. al. CLOVER: A Phase 3 Randomized Trial Investigating the Efficacy and Safety of a Detoxified Toxin A/B Vaccine in Adults 50 Years and Older at Increased Risk of Clostridioides difficile Infection, Clinical Infectious Diseases, 2024;, ciae410. Accessed August 27, 2024. https://doi.org/10.1093/cid/ciae410

2. Parkinson J. Pfizer’s C Difficile Vaccine Did Not Meet Endpoint for Phase 3 Study. Contagion. March 4, 2022. Accessed August 27, 2024. https://www.contagionlive.com/view/pfizer-s-c-difficile-vaccine-did-not-meet-endpoint-for-phase-3-study

HPV vaccine.

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The Advisory Committee on Immunization Practices (ACIP) recommends that adolescents aged 11–12 years receive three vaccines: tetanus, diphtheria, and acellular pertussis (Tdap); quadrivalent meningococcal conjugate (MenACWY); and human papillomavirus (HPV). Providers should continue to advocate for these routine vaccinations and regularly review adolescent vaccination records. Although overall vaccination rates have remained stable, targeted efforts are essential to address the decline in HPV vaccination coverage observed in certain birth cohorts.

In 2023, vaccination coverage for all routine vaccines recommended for adolescents was like that of 2022. Coverage among (Vaccines for Children) VFC-eligible adolescents remained steady during the COVID-19 pandemic, except for a decline in the percentage of those up to date with HPV vaccination by age 13 for individuals born in 2010 compared to those born in 2007. Before the pandemic, there were disparities in coverage between VFC-eligible and non-VFC-eligible adolescents, but these differences have lessened among the most recent birth cohorts surveyed.

“In 2021, approximately 25% of U.S. households reported that a child or adolescent had missed or delayed a health care visit because of the pandemic,” investigators state. “In addition, compared with coverage among adolescents born in 2007, HPV UTD coverage among those born in 2010 decreased 7.1 percentage points overall and 10.3 percentage points among VFC-eligible adolescents.

The CDC analyzed data from the 2023 National Immunization Survey-Teen, which covered 16,658 adolescents aged 13–17, born between January 2005 and December 2010. The analysis aimed to assess vaccination coverage for 2023, track recent trends by birth year, and examine coverage differences based on eligibility for the VFC program.

The report has three main limitations starting with a low household response rate may introduce selection bias. Second, coverage estimates by birth year rely on unequal sample sizes, especially smaller for younger adolescents, which affects precision. Third, coverage estimates for 2023 were notably lower than for 2022, potentially due to changes in survey procedures or reporting methods. Data may also underestimate actual coverage, particularly for HPV, by up to 5.2 percentage points

The next study in MMWR focuses on HPV vaccines, which are also effective in preventing most cervical cancers. Introduced in US-Affiliated Pacific Islands (USAPI) between 2007 and 2016, these vaccines were mainly provided through school-based programs. Assessing adolescent vaccination coverage for tracking progress toward regional goals and identifying areas with low coverage is important. To enhance vaccine access and coverage evidence-based strategies are needed.

As of December 2023, HPV vaccination series initiation among girls aged 13–17 years ranged from 58% in Palau to 97.2% in the Northern Mariana Islands. Completion coverage ranged from 43.4% in Palau to 91.8% in the Northern Mariana Islands. Notably, completion coverage exceeds 90% in the Northern Mariana Islands, and American Samoa is on track to meet WHO goals by 2030.

The investigators note, “The school-located HPV vaccination program is an evidence-based intervention to increase HPV vaccination coverage, particularly in low- and middle-income settings. For example, secondary school enrollmentamong girls is approximately 66% in Federated States of Micronesia, 83% in Marshall Islands, and 80% in Palau, compared with approximately 97% in American Samoa and the Northern Mariana Islands.”

A retrospective analysis using data from jurisdictional immunization information systems estimated HPV vaccination coverage among adolescent girls from 2013 to 2023. The focus was on both initiation and completion of the HPV vaccination series, measuring progress toward the WHO 2030 goal of ≥90% series completion by age 15.

The report has three key limitations, first, the accuracy of coverage estimates relies on the completeness and accuracy of jurisdictional immunization information systems, (IIS) with evaluations showing high data quality since 2016, but earlier data remains unverified. Next, IIS data might overestimate the active patient population due to challenges in tracking migration and deaths, affecting coverage estimates. Lastly, vaccination coverage for Guam, assessed separately via the National Immunization Survey, is not comparable with IIS-based estimates for other USAPI jurisdictions.

In summary, both studies contribute to understanding and improving HPV vaccination coverage by highlighting trends, effectiveness, and regional differences, and they both emphasize the importance of continued monitoring and data collection for tracking progress and improving vaccination rates.

References

1. Pingali C, Yankey D, Chen M, et al. National Vaccination Coverage Among Adolescents Aged 13–17 Years — National Immunization Survey-Teen, United States, 2023. MMWR Morb Mortal Wkly Rep 2024;73:708–714. Accessed August 26, 2024. DOI: http://dx.doi.org/10.15585/mmwr.mm7333a1

2. Suggested citation for this article: Tippins A, Mutamba G, Boyd E, Coy KC, Kriss JL. Human Papillomavirus Vaccination Coverage Among Adolescent Girls Aged 13–17 Years — U.S.-Affiliated Pacific Islands, 2013–2023. MMWR Morb Mortal Wkly Rep 2024;73:715–721. Accessed August 26, 2024. DOI: http://dx.doi.org/10.15585/mmwr.mm7333a2

We are continuing our roundtable series where we delve into important clinical infectious disease topics with a comprehensive discussion with clinicians in the field. This is the first episode of our 3-part series focusing on HIV. Our roundtables are a collaborative project from Contemporary Pediatrics, Contagion, and Contemporary OB/GYN.

This series discusses several aspects of HIV care including clinical management, therapies, vaccines, and multidrug resistance.

In this first episode, the panel offers their approaches to care in terms of medications and management when patients are first diagnosed and a discussion around long-acting injectables for HIV management.

Our panel of clinicians includes:

• MJ Kasten, MD, associate professor of Medicine, consultant, Division of Public Health, Infectious Diseases, and Occupational Medicine, Department of Internal Medicine, Mayo Clinic
• Natasha Hoyte, MPH, CPNP-PC, New York-Presbyterian School Based Health Centers
• Aimalohi Ahonkhai, MD, MPH, associate physician, medicine at the Massachusetts General Hospital, associate director of the Bio-behavioral and Community Science Core and director of the Community Engaged Research Program for the Harvard University Center for AIDS Research
• Jessica Castilho, MD, associate professor of Medicine, Division of Infectious Diseases, associate professor Dept. of Health Policy, Vanderbilt University Medical Center

Stay tuned for future episodes in the coming weeks.

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For decades, peripartum infections have traditionally been treated with ampicillin and gentamicin, plus potentially clindamycin. Yet recent events have sparked a reevaluation of this empiric antimicrobial regimen for such infections: worsening anaerobic organism resistance to clindamycin, an intravenous clindamycin shortage in the US in summer 2023, and recent Clinical and Laboratory Standards Institute changes to the susceptibility breakpoints for aminoglycosides for gram-negative bacteria (eg, Enterobacterales).

Additionally, from an infectious diseases perspective, we tend to think of peripartum infections arising from genitourinary flora. Complicating treatment choices, there are different considerations from an obstetrics/gynecology or neonatology perspective—such as “baby in” or “baby out:—which are very important to review as new regimens move forward. In a 2012 survey of US obstetricians involved in chorioamnionitis care, 212 respondents indicated the use of more than 25 antimicrobial regimens and a wide range of durations, indicating significant clinical variation.¹ Given the rising maternal mortality rate in the US and the knowledge that 14.3% of maternal deaths are a result of infection or sepsis, there is a call to action to optimize management of peripartum infections.²

Intraamniotic infections (IAI) are polymicrobial infections of the amniotic fluid, placenta, fetus, fetal membranes, or decidua with significant implications for both maternal and fetal health if not recognized and treated urgently with intrapartum antibiotics and delivery of the fetus. Chorioamnionitis is one type of IAI that is associated with a 2- to 3.5-fold increased odds of neonatal adverse outcomes depending on gestational age, as well as higher odds of adverse maternal outcomes, including 2.3 higher odds of requiring cesarean delivery.^3-6 Ascension of microorganisms from the vagina into the previously sterile amniotic sac is the primary mechanism of infection, though hematogenous dissemination (Listeria) or introduction after a procedure (eg, amniocentesis, chorionic villus sampling) is also possible.^4,6 A second type of IAI, postpartum endometritis, has a similar microbiology as chorioamnionitis but develops after delivery of the fetus; it represents an infection of the upper genital tract and peritoneal/retroperitoneal space, most often seen after cesarean delivery.^7,8 Additional IAI (eg, septic abortion, pelvic septic thrombophlebitis) could be diagnosed depending on anatomic involvement.

When managing IAI, it is important to rapidly identify pregnant women with infection and initiate antimicrobials. However, there are significant, varied reasons that pregnant women may have a noninfectious fever. There is something unique about the laboring experience that drives fever, and that mechanism is yet to be understood.⁹ Drug exposure (including prostaglandins used to induce labor) and epidural anesthesia are known to cause noninfectious fever in 15% to 25% of pregnant patients; epidural anesthesia may mask other signs of infection (fundal tenderness) or induce other signs of infection (maternal or fetal tachycardia).^9,10 The clinical diagnosis of a peripartum infection such as chorioamnionitis includes presence of fever plus additional clinical factors such as uterine tenderness, purulent amniotic fluid, and other vital sign abnormalities. But there is no gold standard diagnostic test that gives results in a timely fashion (ie, cultures) to say whether a person is infected.⁴ The clinical diagnosis of IAI is clearly critical for both mother and fetus in light of the very serious complications that can occur if antibiotics are not rapidly initiated, but this creates significant clinical variability in identifying infectious versus noninfectious fever because of clinical concern of the serious issues if IAI is missed.

Once IAI is suspected or confirmed, clinicians should consider the likely causative pathogen(s) of infection. There are organisms that should always be considered in IAI, considering the well-noted polymicrobial nature when cultures are obtained. Of high concern is group B streptococci (GBS) due to high colonization rates (10%-30%) at baseline, and the concern that approximately 50% of women who are colonized will transmit the organism to their newborn through vertical transmission during labor or after the rupture of membranes.¹¹ In 2014, the Cochrane Review noted the most commonly isolated organisms in these polymicrobial infections were Mycoplasma hominis, Ureaplasma urealyticum, Chlamydia trachomatis, Neisseria gonorrhea, Trichomonas vaginalis, Bacteroides spp, Gardnerella vaginalis, Escherichia coli, anaerobic streptococcus and GBS.^12,13 Notably, many of these studies referenced in the Cochrane Review use microbiologic data from the 1970s and 1980s, some of which were taken from samples such as placental tissue cultures, amniotic fluid cultures, or vaginal cultures. Many of the peripartum infection Cochrane reviews noted a lack of data upon which to make recommendations; this is a common theme when evaluating peripartum infection data, partially related to ethical concerns about designing trials inclusive of pregnant women. Also worth noting are clinical chorioamnionitis and a slightly different entity of histologic chorioamnionitis, as well as subclinical chorioamnionitis and noninfectious inflammation—so sometimes the data may not correlate with the clinical scenario that the bedside clinician is evaluating.

Furthermore, cultures do not always correlate with the microorganisms identified in the amniotic fluid by RNA gene sequencing, which greatly resemble vaginal flora; it is generally proposed that a dysbiosis occurring, particularly around Lactobacillus, may be generating the predisposition to IAI.⁶This vaginal flora includes organisms not traditionally covered with a “triple therapy” regimen, but the use of triple therapy and its variants still generates a clinical cure. Note that genital mycoplasmas such as Ureaplasma spp and Mycoplasma hominis are found in the lower genital tract of most women. They are noted to provoke robust inflammatory reactions affecting the maternal and fetal compartments, and they are identified in patients with and without signs of clinical IAI.¹⁰ In endometritis and postpartum fevers, results of multiple studies have shown cases involving Gardnerella, Ureaplasma, or Chlamydia trachomatis; however, clinical therapy directed at these organisms was not required for clinical cure.¹⁴ Virulence factors in the genital mycoplasmas may explain their invasive potential, though not their pathogenesis—other organisms such as streptococci have higher pathogenicity.⁶ In an endometritis cohort with Enterococcus spp, a lack of enterococcal coverage did not impact treatment failure rates.¹⁵

Contagion, Summer 2024 Edition

Check out the full Summer 2024 book, now in a new interactive digital format, here:

The American College of Obstetricians and Gynecologists (ACOG) set guidelines for management and published the Intrapartum Management of Intraamniotic Infection committee opinion paper in 2017, which was reaffirmed in 2022.⁴ There are concerns regarding the quality of data on which these recommendations were based, such as the inclusion of antimicrobials that are no longer available or that represent outdated regimens (eg, penicillin monotherapy), and the inclusion of small studies with low numbers of patients enrolled.

Given this is often a clinical diagnosis and that cultures, if even obtained, typically don’t result for a few days, antimicrobial selection for a given patient case is generally empiric. There are multiple studies evaluating different regimens. In 1983, Blanco et al wrote that “the newer cephalosporins are also effective as single-agent therapy,” in reference to using ceftazidime compared with clindamycin and tobramycin in an endometritis cohort, which also had a 9% bacteremia rate. There was no difference in cure rate, side effects, or length of stay.¹⁵ In septic abortion, the combination of ampicillin, gentamicin, and metronidazole was considered universally efficient over the multitude of other regimens utilized clinically. However, Fouks et al noted that piperacillin/tazobactam monotherapy covered 93.3% of all isolates.¹⁶ Logically, broad-spectrum coverage will be successful, but with the urgent public health threat of antimicrobial resistance, narrow-spectrum antimicrobials are preferred whenever possible. The pregnant women population is traditionally considered healthy and without significant antimicrobial resistance, but there are increasing reports of resistance in geographic areas with high gram-negative resistance rates.¹⁷ Regardless of antimicrobial choice, one of the remarkable things about these infections is that a short duration of antibiotics is almost universally agreed upon in the literature.

Enterococcus spp and Ureaplasma spp can be missed in cephalosporin-based regimens, and Ureaplasma spp need the specific addition of azithromycin.⁷ None of the ampicillin, gentamicin, and clindamycin combinations cover genital mycoplasmas. However, this regimen has a greater than 95% success rate in treating maternal infections as well as reducing neonatal sepsis; therefore it is unclear if specific genital mycoplasma coverage is needed.¹⁰ Another analysis noted that when comparing regimens with Bacteroides fragilis activity and those without, there was still an 80% success rate, “raising questions about the type of woman in which a broad-spectrum regimen is necessary.”¹⁸

When confronted with risks such as the emergence of antimicrobial resistance (primarily in Enterobacterales or Bacteroides), changing antimicrobial susceptibility breakpoints (eg, aminoglycosides), and adverse drug events, it is reasonable to consider alternative, modern antimicrobial regimens.⁷ Although ampicillin and gentamicin are primary regimens in IAI, when penicillin allergy regimens plus the potential needs for GBS prophylaxis or surgical site infection prophylaxis in cesarean deliveries are included, there are at least 19 different ACOG-endorsed regimens.^4,11 Cefoxitin was shown to be effective in a real-world cohort study and is endorsed as an “alternative” regimen by ACOG­—one that dodges the clindamycin shortage and gentamicin susceptibility breakpoint changes.¹⁹ Although the additional alternative regimens may be too narrow (ampicillin/sulbactam) or too broad (ertapenem), depending on the microorganisms that are predominant in the local community, there are other Goldilocks-esque regimens that could replace ampicillin/gentamicin plus clindamycin, such as cefoxitin, cefotetan, or piperacillin/tazobactam.

References

1.Greenberg MB, Anderson BL, Schulkin J, Norton ME, Aziz N. A First Look at ChorioamnionitisManagement Practice Variation among US Obstetricians. Infect Dis Obstet Gynecol. 2012;2012:628362. doi:10.1155/2012/628362

2. Pregnancy Mortality Surveillance System | Maternal and Infant Health | CDC. Published March 31, 2023. Accessed April 10, 2024. https://www.cdc.gov/reproductivehealth/maternal-mortality/pregnancy-mortality-surveillance-system.htm

3.Venkatesh K, Glover A, Vladutiu C, Stamilio DM. Association of chorioamnionitis and its duration with adverse maternal outcomes by mode of delivery: a cohort study. BJOG Int J Obstet Gynaecol. 2019;126(6):719-726. doi:10.1111/1471-0528.15565

4.Intrapartum Management of Intraamniotic Infection. Accessed October 10, 2022. https://www.acog.org/en/clinical/clinical-guidance/committee-opinion/articles/2017/08/intrapartum-management-of-intraamniotic-infection

5.Gibbs RS, Dinsmoor MJ, Newton ER, Ramamurthy RS. A randomized trial of intrapartum versus immediate postpartum treatment of women with intra-amniotic infection. Obstet Gynecol. 1988;72(6):823-828. doi:10.1097/00006250-198812000-00001

6. Romero R, Gomez-Lopez N, Winters AD, et al. Evidence that intra-amniotic infections are often the result of an ascending invasion – a molecular microbiological study. J Perinat Med. 2019;47(9):915-931. doi:10.1515/jpm-2019-0297

7. Pek Z, Heil E, Wilson E. Getting With the Times: A Review of Peripartum Infections and Proposed Modernized Treatment Regimens. Open Forum Infect Dis. 2022;9(9):ofac460. doi:10.1093/ofid/ofac460

8.Duff WP. Gabbe’s Obstetrics: Normal and Problem Pregnancies. 58 – Maternal and Perinatal Infection in Pregnancy: Bacterial. 8th ed. Elsevier, Inc; 2021.

9.Goetz l L. Maternal fever in labor: etiologies, consequences, and clinical management. Am J Obstet Gynecol. 2023;228(5):S1274-S1282. doi:10.1016/j.ajog.2022.11.002

10.Tita ATN, Andrews WW. Diagnosis and Management of Clinical Chorioamnionitis. Clin Perinatol. 2010;37(2):339-354. doi:10.1016/j.clp.2010.02.003

11.Prevention of Group B Streptococcal Early-Onset Disease in Newborns. Accessed June 22, 2023. https://www.acog.org/en/clinical/clinical-guidance/committee-opinion/articles/2020/02/prevention-of-group-b-streptococcal-early-onset-disease-in-newborns

12.Chapman E, Reveiz L, Illanes E, Cosp XB. Antibiotic regimens for management of intra‐amniotic infection. Cochrane Database Syst Rev. 2014;(12). doi:10.1002/14651858.CD010976.pub2

13.Czikk MJ, McCarthy FP, Murphy KE. Chorioamnionitis: from pathogenesis to treatment. Clin Microbiol Infect. 2011;17(9):1304-1311. doi:10.1111/j.1469-0691.2011.03574.x

14.Watts DH, Eschenbach DA, Kenny GE. Early Postpartum Endometritis: The Role of Bacteria, Genital Mycoplasmas, and Chlamydia trachomatis. Obstet Gynecol. 1989;73(1):52. Accessed June 15, 2023. https://journals.lww.com/greenjournal/abstract/1989/01000/early_postpartum_endometritis__the_role_of.13.aspx

15.Blanco JD, Gibbs RS, Duff P, Castaneda YS, St Clair PJ. Randomized comparison of ceftazidime versus clindamycin-tobramycin in the treatment of obstetrical and gynecological infections. Antimicrob Agents Chemother. 1983;24(4):500-504. doi:10.1128/aac.24.4.500

16.Fouks Y, Samueloff O, Levin I, Many A, Amit S, Cohen A. Assessing the effectiveness of empiric antimicrobial regimens in cases of septic/infected abortions. Am J Emerg Med. 2020;38(6):1123-1128. doi:10.1016/j.ajem.2019.158389

17.Salmanov AG, Vitiuk AD, Zhelezov D, et al. Prevalence of postpartum endometritis and antimicrobial resistance of responsible pathogens in ukraine: results a multicenter study (2015-2017). Wiadomosci Lek Wars Pol 1960. 2020;73(6):1177-1183.

18.Mackeen AD, Packard RE, Ota E, Speer L. Antibiotic regimens for postpartum endometritis. Cochrane Database Syst Rev. 2015;(2). doi:10.1002/14651858.CD001067.pub3

19. Bailey P, Schacht L, Pazienza G, et al. Cefoxitin for Intra-amniotic Infections and Endometritis: A Retrospective Comparison to Traditional Antimicrobial Therapy Regimens Within a Healthcare System. Clin Infect Dis. Published online January 31, 2024:ciae042. doi:10.1093/cid/ciae042

Pfizer-BioNTech’s COVID-19 Influenza Combination Vaccine Demonstrates Mixed Phase 3 Results

Pfizer announced results from its Phase 3 clinical trial of an investigational COVID-19 and influenza combination vaccine, developed in partnership with BioNTech, along with results from a separate Phase 2 trial of its influenza vaccine. The Phase 3 study focused on two primary immunogenicity objectives: responses to SARS-CoV-2 and to influenza A and B. The combination vaccine met one of these objectives. Notably, the Pfizer tIRV formulation demonstrated strong responses to influenza A, showing consistently higher responses compared to a licensed influenza vaccine. Although, it exhibited lower geometric mean titers and seroconversion rates for the influenza B strain.

The Significance of WHO Declaring Mpox a Global Emergency

Last week, the Africa CDC declared the ongoing mpox outbreak a public health emergency of continental security, while the World Health Organization (WHO) declared it a global health emergency. This announcement marks a significant development in international public health. Mitch Wolfe, MD, vice president of Global Engagement and Governance at Ginkgo Bioworks and former Chief Medical Officer at the CDC, welcomed the WHO’s declaration. He emphasized that it helps unify officials, clinicians, and stakeholders in combating mpox. Wolfe noted, “WHO’s declaration obligates member states to certain actions during outbreaks. It enhances awareness, improves coordination, allocates resources, and prompts countries to consider their response strategies. I’m pleased to see WHO make this declaration early in the outbreak.”

Assessing MRSA Skin and Soft Tissue Infections

Skin and soft tissue infections continue to be a persistent issue in communities and healthcare settings. Methicillin-resistant Staphylococcus aureus (MRSA), once considered a novel threat in the antimicrobial resistance (AMR) battle, has become so prevalent that isolation precautions are often not implemented. Accurately measuring the burden of MRSA is challenging; estimates suggest a 14.69% prevalence in elderly care facilities, while approximately 30% of healthy individuals are colonized with Staphylococcus aureus. Global AMR reports increasingly recognize MRSA not as an emerging threat but as a widespread and endemic infection.

Direct-Acting Antivirals Enhance Outcomes for Chronic Hepatitis C Patients

The impact of direct-acting antivirals (DAAs) on hepatitis C virus (HCV) infection has been a subject of considerable discussion. A recent study conducted by Korea University provides compelling evidence that DAAs significantly enhance clinical outcomes for patients with chronic HCV infection. According to the research, DAAs not only improve liver health but also reduce liver fibrosis, thereby lessening the overall disease burden and extending life expectancy. Published in eClinicalMedicine, this study aimed to evaluate how DAA treatment influences disease burden in HCV-infected patients. By analyzing data from individual participants, researchers found that DAA treatment led to substantial improvements in liver health and a decrease in liver fibrosis-related complications.

FDA Grants EUA for Updated mRNA COVID-19 Vaccines Targeting Omicron Variant KP2

The FDA has granted emergency use authorization for the 2024-2025 mRNA COVID-19 vaccines from Moderna and Pfizer, featuring a component targeting the Omicron KP2 strain. The vaccines aim to enhance protection against current variants and reduce severe outcomes. Eligibility varies: unvaccinated children aged 6 months to 4 years can receive three doses of the Pfizer-BioNTech vaccine or two doses of the Moderna vaccine; previously vaccinated children in this age group are eligible for one or two doses. Children aged 5 to 11 are recommended to get a single dose, while individuals aged 12 and older should receive one dose of the updated vaccines. The FDA will continue to review and adjust guidance based on new data.

CDI

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A recent study aims to compare the effectiveness of vancomycin and metronidazole in achieving event-free survival (EFS) after an initial Clostridioides difficile (C difficile) infection (CDI), using data from a multicenter cohort study conducted in Germany. The findings support recent guideline updates, emphasizing that vancomycin is more effective than metronidazole across all infection severity levels.¹

The study included 489 patients with a first episode of CDI between August 2017 and September 2020. Of these, 118 (24%) were treated with metronidazole and 371 (76%) with vancomycin. Among patients receiving metronidazole, 78 of 118 (66.1%) achieved EFS, compared to 247 of 371 (66.6%) in the vancomycin group. EFS was defined as a response to treatment within ten days, with no recurrence or death within 90 days post-treatment.¹

The IBIS multicenter cohort study included patients with a first episode of CDI between August 2017 and September 2020. EFS was the primary endpoint, defined as a response to treatment with metronidazole or vancomycin within ten days, with no recurrence or death from any cause up to 90 days post-treatment.¹

In the non-severe infection subgroup, 74 of 293 patients (25.3%) received metronidazole, and 219 of 293 (74.7%) received vancomycin. Of these, 33 of 74 (44.6%) in the metronidazole group and 150 of 219 (68.5%) in the vancomycin group achieved EFS. The Cox proportional hazards model indicated that vancomycin was associated with better EFS outcomes compared to metronidazole, with hazard ratios of .46 for all severity levels (95% CI .33-.65), .39 for non-severe infections (95% CI .24-.60), and .52 for severe infections (95% CI .28-.95).¹

The study utilized a Cox proportional hazards model with inverse probability of treatment weighting to assess treatment effectiveness and analyzed data separately for severe and non-severe infections.¹

A related study published in March further supports these findings by examining the impact of CDI treatment on graft-versus-host disease (GVHD) and overall survival in allo-HCT patients. It notes that vancomycin, compared to metronidazole, is associated with lower treatment failure rates and improved outcomes, including reduced rates of GVHD and gastrointestinal GVHD (GI-GVHD). This reinforces the recommendation to use vancomycin or other more effective agents, such as fidaxomicin, as the first-line treatment for CDI.²

In summary, both studies highlight the superior efficacy of vancomycin over metronidazole in treating CDI, with implications for better patient outcomes and fewer complications.

On the contrary, recent research highlights a concerning trend of reduced vancomycin susceptibility in C difficile isolates, impacting patient outcomes negatively. Approximately 34% of isolates showed diminished susceptibility, notably the Ribotype 027 strain. Patients with these less susceptible strains experienced lower rates of sustained clinical response (SCR) and initial cure compared to those with vancomycin-susceptible strains. Specifically, 76% of patients with reduced susceptibility achieved 30-day SCR versus 86% with susceptible strains, and 89% versus 96% for 14-day initial cure.³

The study, conducted from 2016 to 2021, underscores the need for vancomycin susceptibility testing and strain typing in managing C difficile infections. Ongoing surveillance and exploration of patient-specific factors influencing reduced susceptibility to guide treatment strategies amidst rising antimicrobial resistance.³

In conclusion, the German multicenter study confirms that vancomycin is more effective than metronidazole in achieving event-free survival for C difficile infections across all infection severities. Despite these findings, reduced vancomycin susceptibility in some C difficile strains highlights the need for regular susceptibility testing and the consideration of alternative treatments, such as fidaxomicin, to address antimicrobial resistance issues.

References

1. Conrad J, Giesbrecht K, Cruz Aguilar R, et al. Comparative effectiveness of vancomycin and metronidazole on event-free survival after initial infection in patients with Clostridioides difficile – a German multicentre cohort study (IBIS). Clin Microbiol Infect. Published online August 8, 2024. Accessed August 22, 2024. doi: 10.1016/j.cmi.2024.08.003

2. Piekarska A, Sadowska-Klasa A, Mensah-Glanowska P, et al. Effective treatment of Clostridioides difficile infection improves survival and affects graft-versus-host disease: a multicenter study by the Polish Adult Leukemia Group. Sci Rep 14, 5947 (2024). Accessed August 22, 2024. https://doi.org/10.1038/s41598-024-56336-3

3. Eubank T, Dureja C, Garey K, et. al. Reduced Vancomycin Susceptibility in Clostridioides difficile Is Associated With Lower Rates of Initial Cure and Sustained Clinical Response. Clinical Infectious Diseases. February 21, 2024. Accessed August 22, 2024. doi: https://doi.org/10.1093/cid/ciae087