Selection of Antibiotics as Prophylaxis for Close Contacts of Patients with Meningococcal Disease in Areas with Ciprofloxacin Resistance - United States, 2024.

Meningococcal disease, caused by the bacterium Neisseria meningitidis, is a rare but life-threatening illness that requires prompt antibiotic treatment for patients and antibiotic prophylaxis for their close contacts. Historically, N. meningitidis isolates in the United States have been largely susceptible to the antibiotics recommended for prophylaxis, including ciprofloxacin. Since 2019, however, the number of meningococcal disease cases caused by ciprofloxacin-resistant strains has increased. Antibiotic prophylaxis with ciprofloxacin in areas with ciprofloxacin resistance might result in prophylaxis failure. Health departments should preferentially consider using antibiotics other than ciprofloxacin as prophylaxis for close contacts when both of the following criteria have been met in a local catchment area during a rolling 12-month period: 1) the reporting of two or more invasive meningococcal disease cases caused by ciprofloxacin-resistant strains, and 2) ≥20% of all reported invasive meningococcal disease cases are caused by ciprofloxacin-resistant strains. Other than ciprofloxacin, alternative recommended antibiotic options include rifampin, ceftriaxone, or azithromycin. Ongoing monitoring for antibiotic resistance of meningococcal isolates through surveillance and health care providers' reporting of prophylaxis failures will guide future updates to prophylaxis considerations and recommendations.

Immunogenicity and safety of a pentavalent meningococcal ABCWY vaccine in adolescents and young adults: an observer-blind, active-controlled, randomised trial.

BACKGROUND: Meningococcal serogroups A, B, C, W, and Y cause nearly all meningococcal disease, and comprehensive protection requires vaccination against all five serogroups. We aimed to assess the immunogenicity and safety of a pentavalent MenABCWY vaccine comprising two licensed vaccines-meningococcal serogroup B-factor H binding protein vaccine (MenB-FHbp) and a quadrivalent meningococcal serogroup ACWY tetanus toxoid conjugate vaccine (MenACWY-TT)-compared with two doses of MenB-FHbp and a single dose of quadrivalent meningococcal serogroup ACWY CRM197-conjugate vaccine (MenACWY-CRM) as the active control. We previously reported the primary safety and immunogenicity data relating to the two-dose MenB-FHbp schedule. Here we report secondary outcomes and ad-hoc analyses relating to MenABCWY immunogenicity and safety. METHODS: We did an observer-blind, active-controlled trial at 68 sites in the USA, Czech Republic, Finland, and Poland. Healthy individuals (aged 10-25 years) who had or had not previously received a MenACWY vaccine were randomly assigned (1:2) using an interactive voice or web-based response system, stratified by previous receipt of a MenACWY vaccine, to receive 0·5 mL of MenABCWY (months 0 and 6) and placebo (month 0) or MenB-FHbp (months 0 and 6) and MenACWY-CRM (month 0) via intramuscular injection into the upper deltoid. All individuals were masked to group allocation, except staff involved in vaccine dispensation, preparation, and administration; and protocol adherence. Endpoints for serogroups A, C, W, and Y included the proportion of participants who achieved at least a four-fold increase in serum bactericidal antibody using human complement (hSBA) titres between baseline and 1 month after each vaccination. For serogroup B, secondary endpoints included the proportion of participants who achieved at least a four-fold increase in hSBA titres from baseline for each of four primary test strains and the proportion of participants who achieved titres of at least the lower limit of quantitation against all four test strains combined at 1 month after the second dose. Endpoints for serogroups A, C, W, and Y were assessed in the modified intent-to-treat (mITT) population, which included all randomly assigned participants who received at least one vaccine dose and had at least one valid and determinate MenB or serogroup A, C, W, or Y assay result before vaccination up to 1 month after the second dose, assessed in ACWY-experienced and ACWY-naive participants separately. Secondary endpoints for serogroup B were analysed in the evaluable immunogenicity population, which included all participants in the mITT population who were randomly assigned to the group of interest, received all investigational products as randomly assigned, had blood drawn for assay testing within the required time frames, had at least one valid and determinate MenB assay result after the second vaccination, and had no important protocol deviations; outcomes were assessed in both ACWY-experienced and ACWY-naive populations combined. Non-inferiority of MenABCWY to MenACWY-CRM and MenB-FHbp was determined using a -10% non-inferiority margin for these endpoints. Reactogenicity and adverse events were assessed among all participants who received at least one vaccine dose and who had available safety data. This trial is registered with Clinicaltrials.gov, NCT03135834, and is complete. FINDINGS: Between April 24 and November 10, 2017, 1610 participants (809 MenACWY-naive; 801 MenACWY-experienced) were randomly assigned: 544 to receive MenABCWY and placebo (n=272 MenACWY-naive; n=272 MenACWY-experienced) and 1066 to receive MenB-FHbp and MenACWY-CRM (n=537 MenACWY-naive; n=529 MenACWY-experienced). Among MenACWY-naive or MenACWY-experienced MenABCWY recipients, 75·5% (95% CI 69·8-80·6; 194 of 257; serogroup C) to 96·9% (94·1-98·7; 254 of 262; serogroup A) and 93·0% (88·4-96·2; 174 of 187; serogroup Y) to 97·4% (94·4-99·0; 224 of 230; serogroup W) achieved at least four-fold increases in hSBA titres against serogroups ACWY after dose 1 or 2, respectively, in ad-hoc analyses. Additionally, 75·8% (71·5-79·8; 320 of 422) to 94·7% (92·1-96·7; 396 of 418) of MenABCWY and 67·4% (64·1-70·6; 563 of 835) to 95·0% (93·3-96·4; 782 of 823) of MenB-FHbp recipients achieved at least four-fold increases in hSBA titres against MenB strains after dose 2 in secondary analyses; 79·9% (334 of 418; 75·7-83·6) and 74·3% (71·2-77·3; 605 of 814), respectively, achieved composite responses. MenABCWY was non-inferior to MenACWY-CRM (single dose) and to MenB-FHbp in ad-hoc analyses based on the proportion of participants with at least a four-fold increase in hSBA titres from baseline and (for MenB-FHbp only) composite responses. Reactogenicity events after vaccination were similarly frequent across groups, were mostly mild or moderate, and were unaffected by MenACWY experience. No adverse events causing withdrawals were related to the investigational product. Serious adverse events were reported in four (1·5%; 0·4-3·7) MenACWY-naive individuals in the MenABCWY group versus six (2·2%; 0·8-4·8) among MenACWY-experienced individuals in the MenABCWY group and 14 (1·3%; 0·7-2·2) in the active control group (MenACWY-experienced and MenACWY-naive individuals combined); none of these were considered related to the investigational product. INTERPRETATION: MenABCWY immune responses were robust and non-inferior to MenACWY-CRM and MenB-FHbp administered separately, and MenABCWY was well tolerated. The favourable benefit-risk profile supports further MenABCWY evaluation as a simplified schedule compared with current adolescent meningococcal vaccination programmes. FUNDING: Pfizer.

Meningococcal Conjunctivitis in a 54-Year-Old Man: Case Report and Review of the Literature.

Neisseria meningitidis represents an uncommon pathogen of acute bacterial conjunctivitis. In this brief report, we describe a case of meningococcal conjunctivitis in an immunocompetent adult male, with a review of the literature. The patient went to the outpatient ophthalmology clinic complaining of severe ocular discomfort, burning, and redness for more than 2 weeks and, at slit lamp examination, he was diagnosed with a mild conjunctivitis. Microbiology cultures of ocular swabs revealed the growth of colonies, as pure culture, identified as N. meningitidis of serogroup B. A diagnosis of primary meningococcal conjunctivitis was made and treatment of patient with intramuscular injections of ceftriaxone in addition to topical moxifloxacin eye drops for 2 weeks led to clinical improvement and, finally, to a complete recovery, in accordance with microbiological findings. Ophthalmologists must be aware of the possibility of primary meningococcal conjunctivitis cases, even uncommon, and the need to treat with systemic antibiotics and their close contacts with adequate antibiotic chemoprophylaxis.

Meningococcemia in a vaccinated child receiving eculizumab and review of the literature.

BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is a rare and severe disease characterized by uncontrolled activation and dysregulation of the alternative complement pathway and development of thrombotic microangiopathy. Eculizumab, which is used as a first-line therapy in aHUS, blocks the formation of C5 convertase and inhibits the formation of the terminal membrane attack complex. It is known that treatment with eculizumab increases the risk of meningococcal disease by 1000-2000-fold. Meningococcal vaccines should be administered to all eculizumab recipients. CASE: We describe a girl with aHUS who was receiving eculizumab treatment and experienced meningococcemia with non-groupable meningococcal strains which rarely cause disease in healthy people. She recovered with antibiotic treatment and we discontinued eculizumab. CONCLUSIONS: In this case report and review, we discussed similar pediatric case reports in terms of meningococcal serotypes, vaccination history, antibiotic prophylaxis and prognosis of patients who experienced meningococcemia under eculizumab treatment. This case report highlights the importance of a high index of suspicion for invasive meningococcal disease.

A mismatch amplification mutation assay for specific detection of ciprofloxacin-resistant Neisseria meningitidis.

Meningococcal chemoprophylaxis for people in close contact with patients with invasive meningococcal disease (IMD) is necessary for preventing the spread of Neisseria meningitidis. Ciprofloxacin (CIP) is commonly used to treat IMD. However, CIP-resistant N. meningitidis isolates have rapidly evolved worldwide; therefore, rapid and accurate detection of CIP-resistant N. meningitidis is essential. We developed a mismatch amplification mutation assay for identifying gyrA substitutions T91I and D95Y, associated with reduced CIP susceptibility, using two primer sets to detect these variants. Comparison with gyrA sequencing data showed complete congruency. This method enables reliable detection of CIP-resistant N. meningitidis, thus leading to efficient management and control of IMD infections.

Primary septic arthritis of the knee caused by Neisseria meningitidis serogroup B in an elderly patient. Case report and review of the literature.

PURPOSE: Primary meningococcal arthritis (PMA) represents an uncommon clinical presentation of meningococcal infection, mainly reported among young people. Herein, a case of PMA of the knee in an elderly patient is described. CASE PRESENTATION: On January 2022, an 87-year-old patient arrived at hospital with continuous fever persisting for three days and a picture of pain, swelling, redness, and warmth of her left knee. An arthrocentesis was promptly performed and the inoculated synovial fluid turned positive with numerous Gram-negative diplococci at the microscopic examination. The identification of bacteria was done in 48 h using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF) MS systems (VITEK®MS-bioMérieux) and standard microbiological procedures (VITEK®2 NH ID card-bioMérieux). Both methods identified the strain as N. meningitidis. The meningococcal isolate belonged to the serogroup B (MenB), Sequence type (ST)-162/clonal complex (cc)162. Two grams of ceftriaxone twice a day were administered for 21 days; than cefditoren pivoxil 400 mg twice a day for further 6 weeks after discharge. In Italy, from 2018 to January 2022, among 135 MenB, 31 MenB/cc162 were identified, of which only the case here reported was associated with an atypical clinical presentation. REVIEW OF THE LITERATURE: A total of 41 cases of PMA caused by N. meningitidis was reported in the literature, but only four occurred in elderly. To our knowledgements, no cases of PMA caused by MenB were previously reported among patients of more than 65 years of age.

Outcomes of adults with invasive meningococcal disease with reduced penicillin susceptibility in Auckland 2004-2017.

PURPOSE: The purpose of this study was to assess the clinical outcomes of adults with invasive meningococcal disease (IMD) and to compare the outcomes of patients with IMD caused by a penicillin susceptible isolate (minimum inhibitory concentration (MIC) ≤ 0.06 mg/L) with patients with IMD caused by an isolate with reduced penicillin susceptibility (MIC > 0.06 mg/L). We also assessed the outcomes of patients with IMD caused by an isolate with reduced penicillin susceptibility who were treated exclusively with intravenous (IV) benzylpenicillin. METHODS: Retrospective study of all culture positive IMD in adult patients (age ≥ 15 years) in the Auckland region from 2004 to 2017. RESULTS: One hundred and thirty-nine patients were included; 94 had penicillin susceptible isolates (88 cured, 6 died), and 45 had an isolate with reduced penicillin susceptibility (41 cured, 1 possible relapse, 3 died). The median benzylpenicillin/ceftriaxone treatment duration was 3 days for both groups. There was no difference in the patient outcomes of both groups. Eighteen patients with IMD caused by an isolate with reduced penicillin susceptibility received benzylpenicillin alone and were cured. CONCLUSIONS: This study provides further support to existing data that has shown that short duration IV beta-lactam treatment is effective for IMD in adults. Only a small number of patients with meningitis caused by an isolate with reduced penicillin susceptibility received benzylpenicillin alone, limiting its evaluation. For Neisseria meningitidis meningitis, we recommend ceftriaxone as empiric treatment and as definitive treatment when this is caused by an isolate with reduced penicillin susceptibility.

A systematic review and meta-analysis on the antibiotic resistance of Neisseria meningitidis in the last 20 years in the world.

BACKGROUND: Neisseria meningitidis is one of the most important causes of meningitis and pathogens-associated deaths in developing and developed countries. Effective anti-microbial agents are pivotal to treat and control N. meningitidis infections. The aim of the present study was to systematically review published studies on the antibiotic resistance of N. meningitidis in the last 20 years (2000-2020) in the world. METHODS: Published researches were identified through a literature search using reputable databases including PubMed, Scopus, and Web of Science. Finally, 24 studies were included for a random-effects model meta-analysis. RESULTS: The overall resistance to most commonly used antibiotics such as ceftriaxone, cefotaxime, ciprofloxacin and rifampin was low, ranging from 1 to 3.4%. However, non-sensitivity to penicillin, as the first-line antibiotic against N. meningitidis, was higher (27.2%). Altogether, the resistance to the first-line antibiotics (except penicillin) is still low indicating these drugs are effective against meningococcal meningitis. We also found a significant gap between MIC and disk diffusion for evaluating resistance to antibiotics in which disk diffusion overestimate the resistance rate. CONCLUSIONS: To properly management and prevent the spread of N. miningitidis isolates resistant antibiotics, it is necessary to monitor the pattern of antibiotic susceptibility regionally and globally using the MIC methods.

[Recurrent meningococcal infection in a young woman witha mutation in the C8B gene].

This is a case report of recurrent meningococcal infection in a young woman. She had no positive microbiological findings but was serologically diagnosed with the meningococcal antibody test. Investigation of the complement system showed no function of the terminal pathway. Further genetical analysis revealed a pathogen mutation in the C8B gene in the patient and her sister. They were both immunised with meningococcal vaccines. Complement deficiencies are rare but potentially fatal. Workup for complement deficiency is important for correct acute and prophylactic treatment.

Aislamiento de Neisseria meningitidis en muestra anorectal en hombre que tiene sexo con hombre con uretritis y sifilis primaria / Isolation of Neisseria meningitidis in anorectal specimen in a men who have sex with men with uretritis and primary syphilis

Resumen Neisseria meningitidis es una bacteria gramnegativa asociada frecuentemente a enfermedades invasoras de elevada mortalidad. Si bien su reservorio natural es la nasofaringe humana, en los últimos años han aumentado los aislamientos de este agente en la mucosa anorectal, principalmente en hombres que tienen sexo con hombres (HSH). Presentamos el caso de un HSH con infección por VIH, que consultó por un cuadro de uretritis y sifilis primaria, en el cual se aisló N. meningitidis en una muestra anorectal. Fue tratado en forma empírica con ceftriaxona y azitromicina, realizándose un cultivo de control post-tratamiento que fue negativo. A pesar del aumento de las infecciones y colonizaciones anogenitales por N. meningitidis, se desconoce su rol como patógeno genital, en la transmisión de otras infecciones y la necesidad de esquemas terapéuticos específicos.

Abstract Neisseria meningitidis is a Gram-negative bacterium frequently associated with invasive diseases with high mortality. Although its natural reservoir is the human nasopharynx, in recent years there have been increasing reports of isolation of this agent in the anorectal mucosa, mainly in men who have sex with men (MSM). We present the case of an HIV-positive MSM who consulted for urethritis and primary syphilis, in which N. meningitidis was isolated in an anorectal specimen. He was treated empirically with ceftriaxone and azithromycin, and a post-treatment control culture was negative. Despite the increase in anogenital infections and colonization by N. meningitidis, its role is unknown as a genital pathogen and in the transmission of other infections and the need for specific therapeutic regimens.

Penicillin- and Ciprofloxacin-Resistant Invasive Neisseria meningitidis Isolates from Japan.

Neisseria meningitidis causes a life-threatening invasive meningococcal disease (IMD). Isolates resistant to antibiotics, such as penicillin, ceftriaxone, and ciprofloxacin that are recommended for the treatment of IMD patients and their close contacts have been serious public health concerns globally. However, susceptibility profiles to critically important antibiotics and the genetic characteristics of isolates possessing antibiotic resistance are extremely limited as IMD incidence is low in Japan. We assessed the susceptibility profiles of 87 randomly selected, sterile site-derived N. meningitidis strains isolated from hospitals nationwide, recovered between April 1998 and March 2018 in Japan, to seven antibiotics. As a result, we demonstrated, for the first time, that the isolates remained highly susceptible to ceftriaxone, meropenem, azithromycin, ciprofloxacin, chloramphenicol, and rifampin, but not to penicillin. We then characterized the genetic relatedness of six penicillin- and/or ciprofloxacin-resistant isolates obtained in this study with global 112 genomes using core-genome phylogenetic analysis. These results provide the first evidence that invasive lineages such as a penicillin-resistant serogroup W, sequence type (ST)-11 clonal complex (CC), and a ciprofloxacin-resistant serogroup B/C, ST-4821 CC that is considered as a global threat, have been sporadically identified in Japan. Our findings highlight the need to monitor antibiotic resistance in clinical isolates of N. meningitidis, thereby preventing the spread of antibiotic-resistant invasive lineages and maintaining effective treatment for IMD patients and their close contacts. IMPORTANCE Although antibiotics such as penicillin and ceftriaxone can treat invasive meningococcal disease (IMD), the emergence and spread of antibiotic-resistant Neisseria meningitidis have become a global concern. To provide effective treatment, including chemoprophylaxis to IMD patients and their close contacts, we highlighted the importance of recognizing the antibiotic resistance and genetic features of N. meningitidis isolates.

Outbreak of invasive meningococcal disease caused by a meningococcus serogroup B in a nursery school, Wallonia, Belgium, 2018.

Although most invasive meningococcal disease (IMD) cases are sporadic without identified transmission links, outbreaks can occur. We report three cases caused by meningococcus B (MenB) at a Belgian nursery school over 9 months. The first two cases of IMD occurred in spring and summer 2018 in healthy children (aged 3-5 years) attending the same classroom. Chemoprophylaxis was given to close contacts of both cases following regional guidelines. The third case, a healthy child of similar age in the same class as a sibling of one case, developed disease in late 2018. Microbiological analyses revealed MenB with identical finetype clonal complex 269 for Case 1 and 3 (unavailable for Case 2). Antimicrobial susceptibility testing revealed no antibiotic resistance. Following Case 3, after multidisciplinary discussion, chemoprophylaxis and 4CMenB (Bexsero) vaccination were offered to close contacts. In the 12-month follow-up of Case 3, no additional cases were reported by the school. IMD outbreaks are difficult to manage and generate public anxiety, particularly in the case of an ongoing cluster, despite contact tracing and management. This outbreak resulted in the addition of MenB vaccination to close contacts in Wallonian regional guidelines, highlighting the potential need and added value of vaccination in outbreak management.

Primary meningococcal septic arthritis associated with joint calcium oxalate crystals: A case report and review of the literature.

Primary meningococcal septic arthritis (PMSA) is an extremely rare local infection by Neisseria meningitidis in the absence of meningitis or meningococcaemia syndrome. A 30-year-old healthy, immunocompetent man presented with arthralgia, fever, chest rash, and significant swelling of the right knee. On admission, a disseminated maculopapular and purpuric rash, oligoarthritis, neutrophilia, and elevated acute phase reactants were documented. Following arthrocentesis of the right knee, isolation of N. meningitidis and the presence of calcium oxalate crystals in the synovial fluid were reported. The diagnosis of PMSA was made. Histological analysis of the skin lesion showed leucocytoclastic vasculitis. He was treated with intravenous ceftriaxone plus open surgical drainage and ambulatory cefixime with adequate response. After 1 month, he presented resolution of the pathological process. We performed an extensive review of the literature, finding that the key elements supporting the diagnosis of PMSA are prodromal upper respiratory tract symptoms and skin involvement prior to or synchronous with the arthritis. Also, the most frequently involved joint is the knee. This report is the first case of a patient presenting with PMSA associated with calcium oxalate crystals in the synovial fluid. Herein, we discuss the most frequent clinical manifestations, the unusual histological features, the recommended treatment, and the reported prognosis of this rare entity.

The minor pilin PilV provides a conserved adhesion site throughout the antigenically variable meningococcal type IV pilus.

Neisseria meningitidis utilizes type IV pili (T4P) to adhere to and colonize host endothelial cells, a process at the heart of meningococcal invasive diseases leading to meningitis and sepsis. T4P are polymers of an antigenically variable major pilin building block, PilE, plus several core minor pilins that initiate pilus assembly and are thought to be located at the pilus tip. Adhesion of N. meningitidis to human endothelial cells requires both PilE and a conserved noncore minor pilin PilV, but the localization of PilV and its precise role in this process remains to be clarified. Here, we show that both PilE and PilV promote adhesion to endothelial vessels in vivo. The substantial adhesion defect observed for pilV mutants suggests it is the main adhesin. Consistent with this observation, superresolution microscopy showed the abundant distribution of PilV throughout the pilus. We determined the crystal structure of PilV and modeled it within the pilus filament. The small size of PilV causes it to be recessed relative to adjacent PilE subunits, which are dominated by a prominent hypervariable loop. Nonetheless, we identified a conserved surface-exposed adhesive loop on PilV by alanine scanning mutagenesis. Critically, antibodies directed against PilV inhibit N. meningitidis colonization of human skin grafts. These findings explain how N. meningitidis T4P undergo antigenic variation to evade the humoral immune response while maintaining their adhesive function and establish the potential of this highly conserved minor pilin as a vaccine and therapeutic target for the prevention and treatment of N. meningitidis infections.

Primary meningococcal arthritis of the hip due to serogroup W in a pediatric patient.

BACKGROUND: Primary meningococcal arthritis (PMA) is defined as the presence of acute septic arthritis with the identification of Neisseria meningitidis in synovial fluid or blood cultures but no clinical evidence of sepsis or meningitis. This report aimed to describe a clinical case of PMA caused by serogroup W, an uncommon etiology of this disease in Uruguay, and review the available literature. CASE REPORT: We report the case of a 5-year-old female, with no past medical history, admitted to the emergency department with a 12-hour history of fever of 39 °C and a limp. The patient was hemodynamically stable and had no clinical evidence of meningitis. Hip ultrasound showed an increase in synovial fluid. Arthrocentesis showed purulent exudate and synovial fluid culture showed no growth after five days. The blood culture showed isolates of N. meningitidis, serogroup W. The patient received treatment with ceftriaxone, and drainage of the affected joint was performed with excellent clinical response. CONCLUSIONS: Primary meningococcal arthritis is a rare presentation of meningococcal disease. Systematic arthrocentesis and the adequacy of antibiotic therapy when septic arthritis is clinically suspected are essential for confirming the diagnosis and decompressive drainage of the involved joint. This report is the first of PMA caused by serogroup W in Uruguay. Although the most common serogroup involved in meningococcal arthritis is serogroup B in Uruguay, an increase in serogroup W-related diseases has been reported in Chile and Argentina, emphasizing the need for epidemiological surveillance.

Meningococcus, this famous unknown.

Neisseria meningitidis (meningococcus) is a Gram-negative bacterium responsible for two devastating forms of invasive diseases: purpura fulminans and meningitis. Since the first description of the epidemic nature of the illness at the dawn of the nineteenth century, the scientific knowledge of meningococcal infection has increased greatly. Major advances have been made in the management of the disease with the advent of antimicrobial therapy and the implementation of meningococcal vaccines. More recently, an extensive knowledge has been accumulated on meningococcal interaction with its human host, revealing key processes involved in disease progression and new promising therapeutic approaches.

Neisseria meningitidis (méningocoque) est une bactérie à Gram négatif responsable de deux formes gravissimes de maladies invasives : le purpura fulminans et la méningite. Depuis la première description du caractère épidémique de la maladie à l'aube du 19e siècle, les connaissances scientifiques sur les infections méningococciques ont considérablement augmenté. Des progrès majeurs ont été réalisés dans la gestion de la maladie avec l'avènement des agents antimicrobiens et le développement de vaccins contre le méningocoque. De nombreuses connaissances ont récemment été accumulées sur son interaction avec l'être humain, son unique hôte, révélant les processus clés impliqués dans la progression de la maladie et de nouvelles approches thérapeutiques prometteuses.

Acquisition of Ciprofloxacin Resistance Among an Expanding Clade of ß-Lactamase-Positive, Serogroup Y Neisseria meningitidis in the United States.

BACKGROUND: Penicillin and ciprofloxacin are important for invasive meningococcal disease (IMD) management and prevention. IMD cases caused by penicillin- and ciprofloxacin-resistant Neisseria meningitidis containing a ROB-1 ß-lactamase gene (blaROB-1) and a mutated DNA gyrase gene (gyrA) have been recently reported in the United States. METHODS: We examined 2097 meningococcal genomes collected through US population-based surveillance from January 2011 to February 2020 to identify IMD cases caused by strains with blaROB-1- or gyrA-mediated resistance. Antimicrobial resistance was confirmed phenotypically. The US isolate genomes were compared to non-US isolate genomes containing blaROB-1. Interspecies transfer of ciprofloxacin resistance was assessed by comparing gyrA among Neisseria species. RESULTS: Eleven penicillin- and ciprofloxacin-resistant isolates were identified after December 2018; all were serogroup Y, sequence type 3587, clonal complex (CC) 23, and contained blaROB-1 and a T91I-containing gyrA allele. An additional 22 penicillin-resistant, blaROB-1- containing US isolates with wild-type gyrA were identified from 2013 to 2020. All 33 blaROB-1-containing isolates formed a single clade, along with 12 blaROB-1-containing isolates from 6 other countries. Two-thirds of blaROB-1-containing US isolates were from Hispanic individuals. Twelve additional ciprofloxacin-resistant isolates with gyrA T91 mutations were identified. Ciprofloxacin-resistant isolates belonged to 6 CCs and contained 10 unique gyrA alleles; 7 were similar or identical to alleles from Neisseria lactamica or Neisseria gonorrhoeae. CONCLUSIONS: Recent IMD cases caused by a dual resistant serogroup Y suggest changing antimicrobial resistance patterns in the United States. The emerging dual resistance is due to acquisition of ciprofloxacin resistance by ß-lactamase-containing N. meningitidis. Routine antimicrobial resistance surveillance will effectively monitor resistance changes and spread.