Immunogenicity and safety of a quadrivalent meningococcal conjugate vaccine (MenACYW-TT) administered as a booster to adults aged ≥59 years: A phase III randomized study.

This 2-stage Phase III study (NCT04142242) of a recently licensed quadrivalent meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT) assessed the safety and immunogenicity of a booster dose in older adults (≥59 years) primed with either MenACYW-TT or a quadrivalent meningococcal polysaccharide vaccine (MPSV4). Immune persistence of MenACYW-TT and MPSV4 after primary vaccination was also evaluated. During Stage I, the participants administered MPSV4 (n = 165) or MenACYW-TT (n = 236) 3 years previously were randomized 9:2 to receive either a MenACYW-TT booster or to have blood drawn for persistence only. Participants primed with MPSV4 or MenACYW-TT 6-7 years previously had blood drawn for antibody persistence only. A serum bactericidal assay using human complement was used to measure functional antibodies against each serogroup at baseline and, for those receiving a booster, 30 days post-vaccination (D30). Proportions of participants with seroresponse (post-vaccination titers ≥1:16 when baseline titers <1:8 or ≥ 4-fold increase when baseline titers ≥1:8) were determined. Safety data were collected up to D30. Seroresponse rates for all serogroups at D30 ranged from 49.2% to 60.8% in the MPSV4-primed group, and 79.3-93.1% in the MenACYW-TT-primed group. MenACYW-TT induced sufficient seroresponses in each primed group. Geometric mean titers (GMTs) for serogroups C, W, and Y remained or trended higher than pre-vaccination levels at both 3 and 6-7 years after primary vaccination, indicating immune persistence. Safety outcomes were comparable between groups. A MenACYW-TT booster was immunogenic and well tolerated in participants aged ≥59 years regardless of previous quadrivalent meningococcal vaccine received. The greatest immune responses occurred in those primed with MenACYW-TT.

Immunogenicity and safety of MenACWY-TT, a quadrivalent meningococcal tetanus toxoid conjugate vaccine recently licensed in the United States for individuals ≥2 years of age.

Vaccination offers the best way to prevent invasive meningococcal disease (IMD). As demonstrated in countries with national immunization programs (NIPs) against IMD, meningococcal conjugate vaccines have contributed to significant declines in incidence. Since some meningococcal vaccines are associated with modest immunogenicity in infants, possible immunological interference upon concomitant administration with some pediatric vaccines, and administration errors resulting from improper reconstitution, opportunities for improvement exist. A quadrivalent conjugate vaccine, MenQuadfi® (Meningococcal [Serogroups A, C, Y, and W] Conjugate Vaccine; Sanofi, Swiftwater, Pennsylvania), was approved in 2020 for the prevention of IMD caused by meningococcal serogroups A, C, W, and Y in individuals ≥2 years of age in the United States. Five pivotal studies and one ancillary study supported approval in the United States; clinical trials in infants are ongoing. Data on the immunogenicity and safety of this vaccine are presented, and its potential value in clinical practice is discussed.

Persistence of bactericidal antibodies 4 years after a booster dose of quadrivalent meningococcal diphtheria toxoid conjugate vaccine (MenACWY-D).

One dose of quadrivalent meningococcal conjugate vaccine (MenACWY) was first recommended for US adolescents (ages 11-12 years) in 2005 to protect against invasive meningococcal disease (IMD). In 2010, after evidence emerged about waning protection within 5 years after MenACWY vaccination, the US Advisory Committee on Immunization Practices (ACIP) recommended a MenACWY booster at age 16 years. We used a serum bactericidal assay with human complement (hSBA) to evaluate antibody persistence after a MenACWY-D booster in a sample of 110 participants who received the booster 4 years earlier in a phase 2 study. High proportions (89.9-98.2%) of participants maintained hSBA titers (≥1:4) associated with protection against IMD; a majority (81.7-97.2%) also had hSBA titers ≥1:8, a more conservative threshold. These findings support ACIP recommendations regarding MenACWY booster vaccination, which are aimed at protecting adolescents and young adults throughout the period in which they are at increased risk of IMD.

Safety and Immunogenicity of a Full-dose, Split-virion, Inactivated, Quadrivalent Influenza Vaccine in Healthy Children 6-35 Months of Age: A Randomized Controlled Clinical Trial.

BACKGROUND: For children <3 years of age, a half dose of inactivated influenza vaccine (7.5 µg hemagglutinin per strain) has been used for more than 30 years, but several studies indicate that a full dose (15 µg hemagglutinin per strain) can be used in this population without increasing the rate of fever or other reactions. Here, we compare the safety and immunogenicity of full and half doses of quadrivalent, split-virion, inactivated influenza vaccine (IIV4) in children 6-35 months of age. METHODS: In this phase IV, randomized, observer-blinded, multi-center study, healthy children 6-35 months of age were randomized 1:1 to be vaccinated with a half or full dose of IIV4 (NCT02915302). The primary objective was to demonstrate that the rate of any fever (≥38.0°C) up to 7 days after a full dose of IIV4 was noninferior to the rate of fever after a half dose. RESULTS: The study included 1950 children. Noninferiority in the rate of fever was demonstrated for the full dose versus the half dose of IIV4 (difference in rate = 0.84%; 95% confidence interval, -2.13% to 3.80%). Solicited reactions and unsolicited adverse events were similar between the dose groups. No vaccine-related serious adverse events were reported. Noninferiority of both hemagglutination inhibition geometric mean titers and seroconversion rates was demonstrated for all 4 vaccine strains for the full dose versus the half dose. CONCLUSIONS: In children 6-35 months of age, a full dose of IIV4 was immunogenic and had a safety profile comparable to that of a half dose, with no new safety concerns observed.

Gastrointestinal Events in High-Dose vs Standard-Dose Influenza Vaccine Recipients.

Passive surveillance data had signaled the possibility of gastrointestinal adverse events occurring after the administration of high-dose inactivated influenza vaccine (IIV-HD). However, in a large, prospective randomized clinical trial, rates of serious gastrointestinal events were no greater among IIV-HD recipients than among those who received a standard-dose influenza vaccine.

Safety and immunogenicity of a quadrivalent influenza vaccine in adults 65 y of age and older.

Frequent mismatches between the predominant circulating B strain lineage and the B strain lineage in trivalent influenza vaccines have resulted in missed opportunities to prevent influenza illness. Quadrivalent influenza vaccines containing B strains from each of the 2 lineages have been developed for improved prevention of influenza B infections. Here, we describe the results of a phase III, randomized, double-blind, active-controlled, multicenter trial examining the safety and immunogenicity of a split-virion inactivated quadrivalent influenza vaccine (IIV4) in 675 adults ≥ 65 y of age (NCT01218646). Participants were randomly assigned 1:1:1 to receive a single intramuscular injection with the investigational IIV4, or one of 2 split-virion trivalent inactivated influenza vaccines (IIV3s): a licensed IIV3 containing a B Victoria-lineage strain or an investigational IIV3 containing a B Yamagata-lineage strain. Post-vaccination (day 21) hemagglutinin inhibition titers to all strains induced by IIV4 were statistically non-inferior to those induced by the 2 IIV3s. In addition, for each B strain, rates of seroconversion in the IIV4 group were superior to those induced by the comparator IIV3 not containing that B strain. For all vaccines, the most common solicited reaction was injection-site pain, and most reactions were mild to moderate in intensity and transient. Overall safety profiles were similar between IIV4 and the IIV3s, and no vaccine-related serious adverse events were reported. These results confirm that in adults ≥ 65 y of age, IIV4 was well tolerated and immunogenic against the additional B lineage strain without compromising the immunogenicity of the other 3 vaccine strains.

Fluzone® High-Dose Influenza Vaccine.

INTRODUCTION: Fluzone® High-Dose (IIV3-HD) is a trivalent, inactivated, split-virus influenza vaccine indicated for use in older adults (≥65 years of age). It contains 60 µg hemagglutinin of each influenza strain, which is four times the hemagglutinin content of standard-dose influenza vaccines, including Fluzone (IIV3-SD). IIV3-HD has been licensed for use in older adults in the US since December 2009 and in Canada since February 2016. Areas covered: In this review, we summarize postlicensure studies on the immunogenicity, safety, and effectiveness of IIV3-HD and estimates of its cost-effectiveness in older adults. We also discuss the potential application of IIV3-HD in adults 50-64 years of age and in individuals who may respond poorly to standard-dose influenza vaccines. Expert commentary: Multiple studies conducted since 2004 have consistently shown that, in older adults, IIV3-HD induces substantially greater antibody responses and better protection against influenza and influenza-associated hospitalization than IIV3-SD. Health economic analyses suggest that IIV3-HD can be a cost-effective alternative to standard-dose trivalent or quadrivalent inactivated influenza vaccines and can even be cost-saving compared to IIV3-SD in older adults. Further investigation of IIV3-HD vaccination as a way to improve immune responses and protection against influenza in immunocompromised individuals is warranted.

Safety and immunogenicity of a booster dose of meningococcal (groups A, C, W, and Y) polysaccharide diphtheria toxoid conjugate vaccine.

BACKGROUND: Quadrivalent meningococcal conjugate vaccines (MenACWY) were developed to offer long-term protection against invasive disease caused by serogroups A, C, W, and Y. Reduced MenACWY effectiveness within 5 years after primary vaccination (likely due to declining bactericidal antibody titers) has been described, particularly with respect to C and Y disease in the United States. We evaluated the safety and immunogenicity of a single booster dose of quadrivalent meningococcal polysaccharide diphtheria toxoid conjugate vaccine (MenACWY-D) in adolescents and adults who received a previous dose 4-6 years earlier. METHODS: This phase 2, open-label, multicenter study of 834 persons was conducted in the United States. Participants received a single 0.5-mL booster dose of MenACWY-D. Serogroup-specific bactericidal antibody geometric mean titers (GMTs) were measured with a serum bactericidal antibody assay using human complement (hSBA). Proportions of participants achieving antibody titers of ⩾1:8 for each vaccine serogroup on Days 6 and 28 were determined. Rates of adverse events (AEs), including serious adverse events (SAEs), were also assessed. RESULTS: Before booster vaccination, 38.7-68.5% of participants had an hSBA titer ⩾1:8, depending on vaccine serogroup. By Day 6 post-vaccination, 98.2-99.1% of participants had hSBA titers ⩾1:8. By Day 28, >99% of participants achieved this threshold and the primary hypothesis (lower limit of the one-sided 95% confidence limit ⩾85% for each serogroup) was met. The GMT ratios (post-vaccination divided by pre-vaccination) at Day 28 ranged from 47.2 (serogroup A) to 209.1 (serogroup Y). Rates of AEs, including SAEs, were similar to those observed among adolescents and adults who received a primary dose of MenACWY-D in previous studies. There were no study discontinuations due to an AE and no deaths. CONCLUSIONS: Booster vaccination with MenACWY-D was safe and induced robust bactericidal antibody responses, consistent with immune memory, among adolescents and adults 4-6 years after primary vaccination. ClinicalTrials.gov registration: NCT01442675.

Fluzone® Intradermal Quadrivalent Influenza Vaccine.

INTRODUCTION: An intradermal version of Fluzone® split-virion inactivated trivalent influenza vaccine, containing 9 µg hemagglutinin per strain of A/H1N1, A/H3N2, and one B lineage virus (Fluzone Intradermal, Sanofi Pasteur), became available in the US during the 2011-2012 influenza season for adults 18-64 years of age. In advance of the 2015-2016 season, Fluzone Intradermal was replaced with Fluzone Intradermal Quadrivalent vaccine, which contains 9 µg hemagglutinin per strain of the two A-strain viruses and both B-strain lineage viruses (Victoria and Yamagata). AREAS COVERED: This literature review summarizes the history and mechanism of intradermal vaccination, discusses the clinical trial results supporting the immunogenicity and safety of Fluzone Intradermal Quadrivalent vaccine, and describes the unique microinjection system used to deliver Fluzone Intradermal Quadrivalent. Expert commentary: Fluzone Intradermal Quadrivalent may boost confidence in influenza vaccination with the addition of a second B-lineage strain. By using an innovative microinjection system, the vaccine is also designed to address some of the logistic challenges faced by healthcare providers administering immunizations.

Effect of Previous-Year Vaccination on the Efficacy, Immunogenicity, and Safety of High-Dose Inactivated Influenza Vaccine in Older Adults.

BACKGROUND: High-dose inactivated influenza vaccine (IIV-HD) is an alternative to the standard-dose inactivated influenza vaccine (IIV-SD) in the United States for influenza prevention in older adults. IIV-HD improved efficacy relative to IIV-SD in a randomized controlled trial. Recent observational studies suggest that previous influenza vaccination may influence the immunogenicity and effectiveness of current-season vaccination. METHODS: The original study was a double-blind, randomized trial comparing IIV-HD to IIV-SD in adults aged ≥65 years over 2 influenza seasons. A subset of year 1 (Y1) participants reenrolled in year 2 (Y2), receiving vaccine by random assignment in both years. We evaluated the effect of Y1 vaccination on Y2 relative vaccine efficacy (VE), immunogenicity (hemagglutination inhibition [HAI] titers), and safety among reenrolled participants. RESULTS: Of 14 500 Y1 participants, 7643 reenrolled in Y2. Relative to participants who received IIV-SD both seasons, VE was higher for IIV-HD vaccinees in Y2 (28.3% overall; 25.1% for Y1 IIV-HD, Y2 IIV-HD; and 31.6% for Y1 IIV-SD, Y2 IIV-HD). In multivariate logistic regression models, Y1 vaccine was not a significant modifier of Y2 VE (P= .43), whereas Y2 IIV-HD remained significantly associated with lower influenza risk (P= .043). Compared to administration of IIV-SD in both years, postvaccination HAI titers were significantly higher for patterns that included IIV-HD in Y2. No safety concerns were raised with IIV-HD revaccination. CONCLUSIONS: IIV-HD is likely to provide clinical benefit over IIV-SD irrespective of previous-season vaccination with IIV-HD or IIV-SD. IIV-HD consistently improved immune responses, and no safety concerns emerged in the context of IIV-HD revaccination.

Prevention of serious events in adults 65 years of age or older: A comparison between high-dose and standard-dose inactivated influenza vaccines.

BACKGROUND: A recent study showed that a high-dose inactivated influenza vaccine (IIV-HD) was 24.2% more efficacious than a standard-dose inactivated influenza vaccine (IIV-SD) in preventing laboratory-confirmed symptomatic influenza in adults ≥65 years. Here we evaluate the effectiveness of IIV-HD compared to IIV-SD in preventing serious illnesses considered potential sequelae or complications of influenza infection. METHODS: The original study was a double-blind, randomized, active-controlled, multicenter trial. Participants were adults ≥65 years randomized to receive IIV-HD or IIV-SD, and followed for 6-8 months post-vaccination for the occurrence of influenza and serious adverse events (SAEs). SAEs were events: leading to death or hospitalization (or its prolongation); considered life-threatening or medically important; or resulting in disability. For the present analysis, reported SAEs were classified as possibly related to influenza by three blinded physicians and rates per 1000 participant-seasons were calculated. Relative vaccine effectiveness (rVE) was estimated as (1-Rate Ratio)×100. RESULTS: 31,989 participants were enrolled, with 15,991 and 15,998 randomized to receive IIV-HD and IIV-SD, respectively. IIV-HD was significantly more effective than IIV-SD in preventing SAEs possibly related to influenza overall (rVE, 17.7%; 95% confidence interval [CI], 6.6-27.4%) and serious pneumonia (rVE, 39.8%; 95% CI, 19.3-55.1%). Borderline significance was observed for the efficacy of IIV-HD relative to IIV-SD for the prevention of all-cause hospitalizations (rVE, 6.9%; 95% CI, 0.5-12.8%). CONCLUSIONS: Compared to IIV-SD, IIV-HD reduced the risk of SAEs possibly related to influenza. The observed relative effectiveness against serious pneumonia is particularly noteworthy considering the burden of influenza and pneumonia in older adults.

Efficacy and immunogenicity of high-dose influenza vaccine in older adults by age, comorbidities, and frailty.

BACKGROUND: A randomized trial demonstrated that a high-dose inactivated influenza vaccine (IIV-HD) was 24.2% more efficacious than a standard-dose vaccine (IIV-SD) against laboratory-confirmed influenza illness in adults ≥65 years. To evaluate the consistency of IIV-HD benefits, supplemental analyses explored efficacy and immunogenicity by baseline characteristics of special interest. METHODS: Double-blind, randomized, active-controlled, multicenter trial. Adults ≥65 years were randomized 1:1 to receive IIV-HD or IIV-SD and followed for 6-8 months postvaccination for the occurrence of influenza. One third of participants were randomly selected to provide sera for measurement of hemagglutination inhibition antibody (HAI) titers. Efficacy (IIV-HD vs. IIV-SD) against laboratory-confirmed, protocol-defined influenza-like illness (PD-ILI) and HAI geometric mean titer (GMT) ratios (IIV-HD/IIV-SD) were evaluated by age, and number of high-risk comorbid and frailty conditions. RESULTS: Efficacy (95% confidence intervals) of IIV-HD relative to IIV-SD against laboratory-confirmed PD-ILI was 19.7% (0.4%; 35.4%) for participants 65-74 years, 32.4% (8.1%; 50.6%) for those ≥75 years, 22.1% (3.9%; 37.0%) for participants with ≥1 high-risk comorbidity, 23.6% (-3.2%; 43.6%) for those with ≥2 high-risk comorbidities, 27.5% (0.4%; 47.4%) for persons with 1 frailty condition, 23.9% (-9.0%; 47.2%) for those with 2 frailty conditions, and 16.0% (-16.3%; 39.4%) for those with ≥3 frailty conditions. There was no evidence of vaccine efficacy heterogeneity within age, comorbidity, and frailty strata (P-values 0.351, 0.875, and 0.838, respectively). HAI GMT ratios were significantly higher among IIV-HD recipients for all strains and across all subgroups. CONCLUSIONS: Estimates of relative efficacy consistently favored IIV-HD over IIV-SD. There was no significant evidence that baseline age, comorbidity, or frailty modified the efficacy of IIV-HD relative to IIV-SD. IIV-HD significantly improved HAI responses for all strains and in all subgroups. IIV-HD is likely to provide benefits beyond IIV-SD for adults ≥65 years, irrespective of age and presence of comorbid or frailty conditions.

Safety and immunogenicity of an inactivated quadrivalent influenza vaccine in children 6 months through 8 years of age.

BACKGROUND: Strains of 2 distinct influenza B lineages (Victoria and Yamagata) have cocirculated in the United States for over a decade, but trivalent influenza vaccines (TIVs) contain only 1 B-lineage strain. Each season, some or most influenza B disease is caused by the B lineage not represented in that season's TIV. Quadrivalent influenza vaccines (QIVs) containing a strain from each B lineage should resolve this problem. METHODS: This was a Phase III, randomized, multicenter trial in the United States among children 6 months to <9 years of age to evaluate the safety and immunogenicity of inactivated QIV compared with inactivated control TIVs containing opposite B-lineage strains. Participants were randomized at a ratio of approximately 4:1:1 to receive QIV, TIV containing a Victoria-lineage B strain or TIV containing a Yamagata-lineage B strain. Sera were collected pre- and 28-days post-final vaccination and safety was assessed for 6 months after the last injection. RESULTS: A total of 4363 participants were enrolled. QIV induced noninferior antibody responses to all A strains and corresponding B strains compared with the control TIVs and superior antibody responses to the noncorresponding B strain in each TIV. Rates of solicited reactions and unsolicited and serious adverse events were similar in all groups. CONCLUSIONS: This study demonstrated that QIV is safe and immunogenic among children 6 months to <9 years of age. These findings, along with data from 2 other studies of this QIV in adults, suggest that QIV should offer protection against both B lineages with a safety profile similar to TIV across all ages.

Prevention and control of influenza and dengue through vaccine development.

Influenza and dengue are viral illnesses of global public health importance, especially among children. Accordingly, these diseases have been the focus of efforts to improve their prevention and control. Influenza vaccination offers the best protection against clinical disease caused by strains contained within the specific year's formulation. It is not uncommon for there to be a mismatch between vaccine strains and circulating strains, particularly with regards to the B lineages. For more than a decade, two distinct lineages of influenza B (Yamagata and Victoria) have co-circulated in the US with varying frequencies, but trivalent influenza vaccines contain only one B-lineage strain and do not offer adequate protection against the alternate B-lineage. Quadrivalent influenza vaccines (QIVs), containing two A strains (H1N1 and H3N2) and two B strains (one from each lineage) have been developed to help protect against the four strains predicted to be the most likely to be circulating. The QIV section of this article discusses epidemiology of pediatric influenza, importance of influenza B in children, potential benefits of QIV, and new quadrivalent vaccines. In contrast to influenza, a vaccine against dengue is not yet available in spite of many decades of research and development. A global increase in reports of dengue fever (DF) and its more severe presentations, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), suggest that US physicians will increasingly encounter patients with this disease. Similarities of the early signs and symptoms of influenza and dengue and the differences in disease management necessitates a better understanding of the epidemiology, clinical presentation, management, and prevention of DF by US physicians, including pediatricians. The article also provides a brief overview of dengue and discusses dengue vaccine development.

The science of vaccination: establishing safety and efficacy.

Vaccination remains a critically important public health tool. It has been responsible for drastically reducing the occurrence of diseases that were once responsible for invoking extreme fear and anxiety. As a consequence, vaccines themselves, and not the diseases they help prevent, have now become the focus of fear and anxiety for many. This review describes the various activities and systems that are in place to ensure that modern vaccines continue to be safe and effective. A better understanding of existing safeguards may help bolster public confidence in immunization.

Safety and immunogenicity of a quadrivalent inactivated influenza vaccine compared to licensed trivalent inactivated influenza vaccines in adults.

PURPOSE: To evaluate the safety and immunogenicity of a prototype quadrivalent inactivated influenza vaccine (QIV) containing two influenza B strains, one of each lineage, compared with licensed trivalent inactivated influenza vaccines (TIVs) containing either a Victoria B-lineage strain (2009-2010 TIV) or a Yamagata B-lineage strain (2008-2009 TIV). METHODS: Healthy adults ≥18 years of age were eligible to participate in this phase II, open-label, randomized, controlled, multicenter study conducted in the US. Participants received a single dose of 2009-2010 TIV, 2008-2009 TIV, or QIV. Sera were collected before and 21 days after vaccine administration to test for hemagglutination inhibition (HAI) antibodies to each of the four influenza strains. Immunogenicity endpoints included geometric mean HAI antibody titers (GMTs) and rates of seroprotection (titer ≥1:40) and seroconversion (4-fold rise pre- to post-vaccination). Safety endpoints included frequency of solicited injection-site and systemic reactions occurring within 3 days of vaccination, and unsolicited non-serious adverse events (AEs) and serious AEs (SAEs) within 21 days of vaccination. RESULTS: One hundred and ninety participants were enrolled to each vaccine group. QIV induced GMTs to each A and B strain that were noninferior to those induced by the 2009-2010 and 2008-2009 TIVs (i.e., lower limit of the two-sided 95% confidence interval of the ratio of GMT(QIV)/GMT(TIV)>0.66 for each strain). Rates of seroprotection and seroconversion were similar in all groups. Incidence and severity of solicited injection-site and systemic reactions, AEs, and SAEs were similar among groups. CONCLUSION: QIV, containing two B strains (one from each B lineage), was as safe and immunogenic as licensed TIV. QIV has the potential to be a useful alternative to TIV and offer protection against both B lineages.

Hepatitis B outbreak associated with a hematology-oncology office practice in New Jersey, 2009.

BACKGROUND: Transmission of bloodborne pathogens due to breaches in infection control is becoming increasingly recognized as greater emphasis is placed on reducing health care-associated infections. Two women, aged 60 and 77 years, were diagnosed with acute hepatitis B virus (HBV) infection; both received chemotherapy at the same physician's office. Due to suspicion of health care-associated HBV transmission, a multidisciplinary team initiated an investigation of the hematology-oncology office practice. METHODS: We performed an onsite inspection and environmental assessment, staff interviews, records review, and observation of staff practices. Patients who visited the office practice between January 1, 2006 and March 3, 2009 were advised to seek testing for bloodborne pathogens. Patients and medical providers were interviewed. Specimens from HBV-infected patients were sent to the Centers for Disease Control and Prevention for HBV DNA testing and phylogenic analysis. RESULTS: Multiple breaches in infection control were identified, including deficient policies and procedures, improper hand hygiene, medication preparation in a blood processing area, common-use saline bags, and reuse of single-dose vials. The office practice was closed, and the physician's license was suspended. Out of 2,700 patients notified, test results were available for 1,394 (51.6%). Twenty-nine outbreak-associated HBV cases were identified. Specimens from 11 case-patients demonstrated 99.9%-100% nucleotide identity on phylogenetic analysis. CONCLUSION: Systematic breaches in infection control led to ongoing transmission of HBV infection among patients undergoing invasive procedures at the office practice. This investigation underscores the need for improved regulatory oversight of outpatient health care settings, improved infection control and injection safety education for health care providers, and the development of mechanisms for ongoing communication and cooperation among public health agencies.

Investigation of an apparent outbreak of Rhodococcus equi bacteremia.

During January to April 2007, hospital staff reported 3 patients with Rhodococcus equi bloodstream infections. Isolates were analyzed at the Centers for Disease Control and Prevention, Atlanta, GA, to confirm identification and to assess strain relatedness; 2 were R. equi but genetically distinct, and 1 was identified as Gordonia polyisoprenivorans. Rapid reference laboratory support prevented an unnecessary outbreak investigation.