Neisseria meningitidis with decreased susceptibility to penicillin G and molecular characterization of the penA gene in strains isolated at University Hospital Centers of Casablanca and Marrakech (Morocco).

Introduction: the laboratory diagnosis of meningococcal meningitis relies on conventional techniques. This study aims to evaluate the correlation between the reduced sensitivity to penicillin G of Neisseria meningitidis (N.m) strains and the expression of the altered PBP 2 gene. Methods: out of 190 strains of N.m isolated between 2010 and 2021 at the bacteriology laboratories of Ibn Rochd University Hospital Centre (IR-UHC) in Casablanca and the UHC Mohammed VI in Marrakech, 23 isolates were part of our study. We first determined their state of sensitivity to penicillin G by E-Test strips and searched for the expression of the penA gene by PCR followed by Sanger sequencing. Results: of all the confirmed cases of N.m, 93.15% (n=177) are of serogroup B, 75.2% (n = 143) are sensitive to penicillin G and 24.73% (n = 47) are of intermediate sensitivity. No resistance to penicillin G was observed. Reduced sensitivity to penicillin G in N.m is characterized by mutations namely F504 L, A510 V, I515 V, G541 N and I566 V located in the C-terminal region of the penA gene encoding the penicillin-binding protein 2 (PBP2) (mosaic gene). Conclusion: our study presents useful data for the phenotypic and genotypic monitoring of resistance to penicillin G in N.m and can contribute to the analysis of genetic exchanges between different Neisseria species.

Antibiotic resistance among invasive Neisseria meningitidis isolates in England, Wales and Northern Ireland (2010/11 to 2018/19).

Invasive meningococcal disease (IMD), caused by Neisseria meningitidis, can have a fatality rate as high as 10%, even with appropriate treatment. In the UK, penicillin is administered to patients in primary care whilst third generation cephalosporins, cefotaxime and ceftriaxone, are administered in secondary care. The first-choice antibiotic for chemoprophylaxis of close contacts is ciprofloxacin, followed by rifampicin. Immunocompromised individuals are often recommended antibiotic chemoprophylaxis and vaccination due to a greater risk of IMD. Resistance to antibiotics among meningococci is relatively rare, however reduced susceptibility and resistance to penicillin are increasing globally. Resistance to third generation cephalosporins is seldom reported, however reduced susceptibility to both cefotaxime and ceftriaxone has been observed. Rifampicin resistance has been reported among meningococci, mainly following prophylaxis, and ciprofloxacin resistance, whilst uncommon, has also been reported across the globe. The Public Health England Meningococcal Reference Unit receives and characterises the majority of isolates from IMD cases in England, Wales and Northern Ireland. This study assessed the distribution of antibiotic resistance to penicillin, rifampicin, ciprofloxacin and cefotaxime among IMD isolates received at the MRU from 2010/11 to 2018/19 (n = 4,122). Out of the 4,122 IMD isolates, 113 were penicillin-resistant, five were ciprofloxacin-resistant, two were rifampicin-resistant, and one was cefotaxime-resistant. Penicillin resistance was due to altered penA alleles whilst rifampicin and ciprofloxacin resistance was due to altered rpoB and gyrA alleles, respectively. Cefotaxime resistance was observed in one isolate which had an altered penA allele containing additional mutations to those harboured by the penicillin-resistant isolates. This study identified several isolates with resistance to antibiotics used for current treatment and prophylaxis of IMD and highlights the need for continued surveillance of resistance among meningococci to ensure continued effective use.

Identification and structural investigation of potential novel drug candidates against lethal human pathogen.

Neisseria meningtidis is responsible for causing meningococcal meningitis along with acute septicaemia in human beings. Functional genomics strategies proved cruciality of certain genes/proteins in Neisseria meningitidis pathogenesis. During the present studies, three important Neisseria meningitidis proteins i.e., Dead box RNA-Helicase, Polyribonucleotide nucleotidyl-transferase PNPase and Ribonuclease-III were targeted for homology modeling and protein-ligand docking studies not only to determine their three dimensional architectures but also to identify their potential novel inhibitors. The Biscoumarin, malonitrile and indole derivatives showed the best inhibitory mode against all of the three enzymes. Since, these enzymes are assembled in Gram-negative bacteria to form RNA degradosome assembly therefore their inhibition will definitely shut off the degradosome assembly and ultimately the decay of RNA, which is an essential life process. This is the first ever structural investigation of these drug targets along with identification of potential novel drug candidates. We believe that these small chemical compounds will be proved as better drugs and will provide an excellent barrier towards Neisseria meningitidis pathogenesis.

Peritonitis primària per N. meningitidis serogrup B / Peritonitis primaria por N. Meningitidis serogrupo B / Primary peritonitis by serogroup B N. Meningitidis

INTRODUCCIÓ: Neisseria meningitidis és un dels principals causants de sèpsia I meningitis adquirida a la comunitat en pacients pediàtrics. Se'n descriuen presentacions atípiques, com la peritonitis primària. Presentem aquest cas per la seva excepcionalitat: una patologia infreqüent en edat pediàtrica causada per un germen poc habitual. CAS CLÍNIC: Es presenta un lactant de 4 mesos que acut al servei d'Urgències amb els seus pares per febre I lesions cutànies disseminades de 24 hores d'evolució, amb vòmits I diarrea. Davant la sospita de sèpsia, s'inicien maniobres de reanimació inicial, amb càrrega de volum I antibioteràpia, prèvia extracció d'hemocultiu. Tot I la millora clínica inicial, persisteix la palpació dolorosa a l'hipogastri. Es valora juntament amb Cirurgia I es fa una tomografia computada abdominal que mostra hipercaptació de nanses d'intestí prim I líquid intraabdominal compatible amb procés inflamatori peritoneal. Es fa una laparoscòpia exploradora I s'obté abundant líquid purulent; es revisen íntegrament budell I colon sense observar lesions. Es manté a dieta absoluta durant 48 hores després de la cirurgia, amb progressió alimentària posterior sense incidències. S'obtenen resultats microbiològics: hemocultiu positiu per N. meningitidis B I reacció en cadena de la polimerasa N. meningitidis positiva en sang I en líquids cefalorraquidi I peritoneal. COMENTARIS: La peritonitis primària en pacients pediàtrics sans és una entitat de baixa incidència. Entre els gèrmens descrits en la literatura és molt poc freqüent trobar N. meningitidis. És necessari pensar en aquesta entitat davant d'un pacient amb malaltia invasiva per N. meningitidis I exploració abdominal patològica. La base del tractament són la cirurgia I l'antibioteràpia endovenosa

INTRODUCCIÓN: Neisseria meningitidis es una de las principales causas de sepsis y meningitis adquirida en la comunidad en pacientes pediátricos. Se describen presentaciones atípicas entre las cuales consta de forma excepcional la peritonitis primaria. Este caso ha sido seleccionado por su excepcionalidad, pues se trata de una patología poco frecuente en edad pediátrica y causada por un germen poco habitual. CASO CLÍNICO: Se presenta a un lactante de 4 meses que acude al servicio de Urgencias con sus padres por fiebre y lesiones cutáneas diseminadas de 24 horas de evolución, junto con vómitos y diarrea. Ante la sospecha de sepsis se realizan maniobras de reanimación inicial con carga de volumen y antibioterapia, con previa toma de hemocultivo. A pesar de la mejoría clínica inicial, persiste palpación dolorosa en hipogastrio. Se valora junto con Cirugía y se realiza tomografía computarizada abdominal que muestra hipercaptación de asas de intestino delgado, asociado a líquido intra-abdominal compatible con proceso inflamatorio peritoneal. Se realiza laparoscopia exploradora y se obtiene abundante líquido purulento y esfacelos; se revisan de forma íntegra intestino y colon sin observar lesiones. Se mantiene a dieta absoluta durante 48 horas tras la cirugía, con progresión alimentaria posterior y sin incidencias. Se obtienen resultados microbiológicos: hemocultivo positivo para N. meningitidis B sensible y reacción en cadena de la polimerasa N. meningitidis B positiva en sangre y en líquidos cefalorraquídeo y peritoneal. COMENTARIOS: La peritonitis primaria en pacientes pediátricos sanos es una entidad de baja incidencia. Entre los gérmenes descritos en la literatura es muy poco frecuente encontrar N. meningitidis. Es necesario pensar en esta entidad ante un paciente con infección invasiva por N. meningitidis con exploración abdominal patológica. La base de su tratamiento son la cirugía y la antibioterapia endovenosa

INTRODUCTION: Neisseria meningitidis is one of the main causes of community acquired sepsis and meningitis in children. Atypical presentations have been described, one of them is primary peritonitis. CASE REPORT: We present a 4-month-old infant admitted to the emergency department with fever and disseminated petechia of 24 hours of evolution along with vomiting and diarrhea. With the diagnosis of sepsis, resuscitation maneuvers were started with intravenous fluids and antibiotics after a blood culture was obtained. In spite of the initial clinical improvement, painful palpation persisted in hypogastrium. The patient was assessed together with surgery and an abdominal computed tomography was performed, which showed a small intestine loop enlargement, associated with intraabdominal fluid that suggested peritonitis. Exploratory laparoscopy was performed, obtaining abundant purulent fluid and necrotic and inflammatory tissue. The entire bowel and colon were inspected and no lesions were found. The patient remained fasting for 48 hours after surgery. Enteral nutrition was started afterwards with no complications. N. menigitidis B was isolated in blood culture and polymerase chain reaction positive for N. meningitidis B was positive in blood and in cerebrospinal and peritoneal fluids. COMMENTS: Primary peritonitis in healthy pediatric patients is rare. N. meningitidis is very rare causative pathogen. Primary peritonitis should be considered when having a patient with invasive infection by N. meningitidis with abnormal abdominal examination. Treatment includes surgery and intravenous antibiotics

Antibiotic susceptibility and molecular analysis of invasive Neisseria meningitidis recovered in the Republic of Ireland, 1996 to 2016.

This study examined the antimicrobial susceptibility of invasive meningococcal disease (IMD)-associated Neisseria meningitidis recovered in the Republic of Ireland between 1996 and 2016. In total, 1359 isolates representing over one-third of all laboratory-confirmed cases of IMD diagnosed each epidemiological year (EY; July 1-June 30) were analysed. All isolates were susceptible to ciprofloxacin, rifampicin and cefotaxime and 74% and 87% were susceptible to sulphonamide and penicillin, respectively. The proportion of isolates exhibiting reduced susceptibility to penicillin increased significantly during the study with no evidence of major clonal expansion or horizontal spread of a specific penA allele. Greater diversity observed among recently recovered meningococci and specifically among isolates exhibiting reduced penicillin susceptibility contributed to the overall increase in penA allele diversity throughout. The emergence and dissemination of strains with phenotypic and genotypic reduced susceptibility to penicillin increase the need for continued surveillance of antimicrobial susceptibility of meningococci in the Republic of Ireland especially in view of the recommendation of penicillin G as empiric treatment of choice for pre-hospital management.

Emergence of ciprofloxacin-resistant Neisseria meningitidis B from asymptomatic carriers during an outbreak in Peru, 2017.

Asymptomatic carriers are a likely source of transmission of Neisseria meningitidis to close contacts who are placed at a higher risk for invasive meningococcal disease (IMD). Although N. meningitidis ciprofloxacin-resistance is rare, there have been an increase in the reports of resistant isolates mainly in patients diagnosed with IMD, and little is known about the N. meningitidis ciprofloxacin-resistance in the carrier populations. We performed a pharyngeal carriage study during a 2017 military setting outbreak in Peru, caused by a ciprofloxacin-resistant N. meningitidis B. The isolates analysed came from two hospitalized cases and six asymptomatic carriers. Whole-genome sequence-based analysis was performed and showed that strains carrying the Thr91Ile mutation, in the gene encoding for subunit A of DNA gyrase (gyrA), were responsible for the fluoroquinolone resistance (MICs ≥0.256 µg ml-1) and were closely related to highly virulent strains from France, Norway and the UK. Phylogenetic analysis of the gyrA gene revealed that likely these Peruvian isolates acquired resistance through horizontal gene transfer from Neisseria lactamica. Our study provides evidence for the emergence and propagation of ciprofloxacin-resistant N. meningitidis B from asymptomatic carriers, and recommends the introduction of serogroup B vaccines for high-risk populations.

Epidemiology and antibiotic resistance profile of bacterial meningitis in Morocco from 2015 to 2018.

Over a 4-year study period from 2015 to 2018, altogether 183 isolates of bacterial meningitis were collected from 12 hospitals covering the entire Moroccan territory. Neisseria meningitidis represented 58.5%, Streptococcus pneumoniae 35.5%, and Haemophilus influenzae type b 6%. H. influenzae type b mainly affected 5-year-olds and unvaccinated adults. N. meningitidis serogroup B represented 90.7% followed by serogroup W135 with 6.5%. Decreased susceptibility to penicillin G (DSPG) for all isolates accounted for 15.7%, with 11.6% being resistant to penicillin G (PG) and 4.1% decreased susceptibility. Cumulative results of all strains showed 2.7% decreased susceptibility to amoxicillin and 3.3% resistant, 2.2% of isolates were resistant to third-generation cephalosporin and 2.2% were decreased susceptible, 5.5% were resistant to chloramphenicol and 2.7% were resistant to rifampin. The frequency of DSPG observed in our study is more common in S. pneumoniae than in N. meningitidis (P < 0.05). These isolates have been found to be highly susceptible to antibiotics used for treatment and prophylaxis chemotherapy and the observed resistance remains rare. The impact of introduction of conjugate vaccines against H. influenzae type b and S. pneumoniae (PCVs) is an advantage in reducing meningitis cases due to these two species.

Australian Meningococcal Surveillance Programme annual report, 2019.

Invasive meningococcal disease (IMD) is a notifiable disease in Australia, and both probable and laboratory-confirmed cases of IMD are reported to the National Notifiable Diseases Surveillance System (NNDSS). In 2019, there were 206 notifications of IMD. Of these, 202 were laboratory-confirmed cases analysed by the reference laboratories of the Australian National Neisseria Network (NNN). Of the 202 laboratory-confirmed cases of IMD, 167 were confirmed by bacterial culture and 35 by nucleic acid amplification testing, and all had the serogroup determined. Fine typing was available on 146 samples (146/202, 72%). Neisseria meningitidis serogroup B (MenB) infections accounted for 50.0% (101/202); MenW for 26.2% (53/202); MenY for 20.8% (42/202) and MenC for 3.0% of cases (6/202). Of the MenW cases, 88% were PorA antigen type P1.5,2, and 65% of these (24/37) were sequence type 11, the hypervirulent strain reported in recent outbreaks in Australia and overseas. The primary peaks of IMD notifications in Australia in 2019 were observed in infants less than 1 year of age (36/202, 18%) and in adults aged 65 years or older (39/202, 19%). MenB infections predominated in those aged less than 5 years and those aged 15-19 years, whereas MenW and MenY infections predominated in those aged 45 years or more. All 167 IMD isolates were tested for antimicrobial susceptibility. One isolate out of these 167 (0.6%) was resistant to penicillin with an MIC ≥ 1mg/L; 154/167 isolates (92%) had decreased susceptibility to penicillin. All isolates were susceptible to ceftriaxone and ciprofloxacin, and one isolate was resistant to rifampicin.

First report of meningococcal ciprofloxacin resistance in Greece due to invasive isolates of the sequence type ST-3129.

A local outbreak caused by Neisseria meningitidis occurred in the migration camp in the Greek island of Lesbos during January-February 2020 (4 of 5 cases). In total, 5 samples positive for N. meningitidis were further investigated for sero-/genogroup, PorA, and WGS analysis. MenB was found among 3 cases, while in two cases, MenY was identified. WGS analysis and antibiotic susceptibility testing on the 2 culture positive MenB samples showed the new ST-3129, ciprofloxacin-resistant clone was circulating among the immigrants in the aforementioned camp. This is the first report of ciprofloxacin resistance in Greece.

Detection of Ciprofloxacin-Resistant, ß-Lactamase-Producing Neisseria meningitidis Serogroup Y Isolates - United States, 2019-2020.

Meningococcal disease is a sudden-onset, life-threatening illness caused by the bacterium Neisseria meningitidis. Prompt empiric antibiotic treatment can reduce morbidity and mortality among patients, and antibiotic prophylaxis can prevent secondary disease in close contacts. Historically, N. meningitidis isolates in the United States have largely been susceptible to the antibiotics recommended for treatment and prophylaxis, including penicillin and ciprofloxacin. This report describes detection of penicillin-resistant and ciprofloxacin-resistant N. meningitidis serogroup Y (NmY) isolates in the United States. NmY isolates containing a blaROB-1 ß-lactamase enzyme gene conferring resistance to penicillins (1) were recovered from 33 cases reported during 2013-2020. Isolates from 11 of these cases, reported during 2019-2020, harbored a ciprofloxacin resistance-associated mutation in a chromosomal gene (gyrA). Cases were reported from 12 geographically disparate states; a majority of cases (22 of 33, 67%) occurred in Hispanic persons. These cases represent a substantial increase in penicillin-resistant and ciprofloxacin-resistant meningococci in the United States since 2013. Ceftriaxone and cefotaxime, the recommended first-line agents for empiric bacterial meningitis treatment, can continue to be used for treatment, but health care providers should ascertain susceptibility of meningococcal isolates to penicillin before switching to penicillin or ampicillin. Ongoing monitoring for antimicrobial resistance among meningococcal isolates and prophylaxis failures will be important to inform treatment and prophylaxis recommendations.

Neisseria meningitidis aislada de muestras de hombres que tienen sexo con hombres / Neisseria meningitidis isolated from patients in men who have sex with men

Resumen En los períodos 2000-2004 y 2014-2015 se investigó la presencia de Neisseria meningitidis en 1.143 y 544 hombres que tienen sexo con hombres respectivamente, atendidos en el marco de un programa de enfermedades de transmisión sexual. Se determinó la prevalencia de este agente, su distribución en serogrupos y su sensibilidad a los antimicrobianos. Se obtuvieron hisopados faríngeos, rectales y uretrales, que se sembraron en medio selectivo Thayer Martin modificado. La identificación se realizó mediante pruebas bioquímicas convencionales y por espectrometría de masas (MALDI-TOF). En el segundo período estudiado, sobre 85 aislamientos procedentes de faringes se investigaron los serogrupos B, C, W e Y mediante PCR. Se determinó la CIM de penicilina, ceftriaxona, rifampicina, azitromicina y ciprofloxacina en 66 aislamientos obtenidos en el primer período y en 102 logrados en el segundo. La prevalencia de N. meningitidis fue del 17,8% en el primer período y del 28,1% en el segundo; este microorganismo se aisló más frecuentemente de fauces. Los serogrupos hallados fueron B (31,5%), Y (7,6%) y W (3,3%), con un 9,8% de aislamientos no capsulados; los restantes corresponderían a otros serogrupos. El 34,8% y el 63,7% de los aislados estudiados correspondientes al primer y segundo período, respectivamente, tuvieron sensibilidad intermedia a la penicilina, y un 11,8% de los evaluados en el segundo período fueron resistentes a dicho antibiótico. Todos los aislados estudiados fueron sensibles a ceftriaxona y a ciprofloxacina (excepto 3, con CIM entre 0,25 y 0,5(g/ml), el 3% fueron resistentes a rifampicina y el 2% fueron no sensibles a azitromicina. La portación de N. meningitidis en hombres que tienen sexo con hombres fue elevada y hubo un alto porcentaje de cepas no sensibles a penicilina. El serogrupo B fue prevalente.

Abstract During the periods 2000-2004 and 2014-2015, Neisseria meningitidis was investigated in men who have sex with men, 1143 and 544 respectively, who consulted in the sexually-transmitted disease program. Prevalence, serogroup distribution and susceptibility to antibiotics were determined. Pharyngeal, rectal and urethral swabs were cultivated on selective Thayer-Martin modified medium. The identification was performed by biochemical tests and mass spectrometry by MALDI-TOF. Serogroups B, C, W and Y were investigated by PCR in 85 isolates recovered from the pharynx belonging to the second period. MICs of penicillin, ceftriaxone, rifampicin, azithromycin and ciprofloxacin were determined for 66 and 102 isolates from periods 1 and 2 respectively, according to CLSI. The prevalence of N. meningitidis was 17.8% and 28.1%, in periods 1 and 2 respectively; the isolates were mainly recovered from the pharynx. The distribution of serogroups was B 31.5%; Y 7.6%; W 3.3% and 9.8% non-capsulated and the rest would belong to other serogroups. Isolates classified as intermediate to penicillin were 34.8% and 63.7% (first and second periods, respectively); moreover, 11.8% of the isolates from the second period were resistant. All isolates were susceptible to ceftriaxone, to ciprofloxacin (except 3 isolates with MIC values between 0.25 and 0.5(g/ml), 3% were resistant to rifampicin and 2% were not susceptible to azithromicin. The prevalence of N. meningitidis carriage in men who have sex with men was high with a high rate of penicillin non-susceptible isolates. B was the prevalent serogroup.

Carriage rate of Neisseria meningitidis, antibiotic susceptibility pattern and associated risk factors among primary school children in Gondar town, Northwest Ethiopia.

BACKGROUND: Globally, in 2012, about 1.2 million estimated cases were reported with ~ 135,000 deaths annually. In Ethiopia, specifically in our study area, limited information is found on the oropharyngeal carriage, antimicrobial resistance pattern, and associated risk factors for N. meningitidis among school children. So, the aim of this study was to assess oropharyngeal carriage rate of N. meningitidis, antibiotic susceptibility pattern and associated risk factors among primary school children in Gondar town, Northwest Ethiopia. METHODS: A cross sectional study was conducted from January to April, 2019 in Gondar town. Multi stage simple random sampling technique was used. A total of 524 oropharyngeal swabs were collected using sterile plastic cotton swabs. Modified Thayer Martin media was used for primary isolation. Antimicrobial susceptibility pattern was done based on Kirby-Bauer method on Muller-Hinton agar supplemented with 5% sheep blood. Multidrug resistance was defined as resistance of an isolate to two or more antimicrobial classes tested. Logistic regression model was used to see the association between dependent variables (Carriage rate of Neisseria meningitidis, Serogroups of Neisseria meningitidis and Antimicrobial susceptibility patterns) and independent variables (Socio-demographic data and risk factors). Variables with a P- value ≤0.2 during bivariable analysis was taken to multivariable analysis to check significant association of meningococcal carriage with risk factors. Finally, a P-value < 0.05 was considered as statistically significant. Data was summarized using numbers, percentages and tables. RESULTS: A total of 53(10.1%) (CI: 7.6-12.8) N. meningitidis isolates were identified. Serogroup A 13 (24.5%) was the most prevalent followed by Y/W135 11(20.7%) whereas serogroup B 4(7.6%) was the least identified serotype. Meningococcal isolates were resistant to ciprofloxacin (45.3%) and trimethoprim-sulfamethoxazole (73.6%). Overall, most of meningococcal isolates showed about 32(60.4%) multidrug resistance. Meningococcal carriage rate was significantly associated with family size, tonsillectomy, passive smoking, number of students per class, sharing utensils, history of visiting healthcare institutions, and indoor kitchen. CONCLUSION: This study highlights the need for reinforcement of case-based, laboratory confirmed surveillance of N. meningitidis carriage in Ethiopian elementary school students to enable mapping of distribution of serotypes of the causative organisms across the country and determine the current potential necessity of vaccination.

The spread of chloramphenicol-resistant Neisseria meningitidis in Southeast Asia.

OBJECTIVES: Invasive disease caused by Neisseria meningitidis is a significant health concern globally, but our knowledge of the prevailing serogroups, antimicrobial susceptibility patterns, and genetics of N. meningitidis in Southeast Asia is limited. Chloramphenicol resistance in N. meningitidis has rarely been reported, but was first described in isolates from Vietnam in 1998. We aimed to characterise eight chloramphenicol resistant meningococcal isolates collected between 2007 and 2018 from diagnostic microbiology laboratories in Cambodia, Thailand and the Lao People's Democratic Republic (Laos). METHODS: Whole-genome sequencing was used to generate genome sequences from 18 meningococcal isolates including the eight chloramphenicol resistant isolates. We identified antimicrobial resistance genes present in these strains, and examined the phylogenetic relationships between strains. RESULTS: The eight resistant strains all contain the same chloramphenicol resistance gene first described in 1998, and are closely related to each other. Strains resistant to penicillin, tetracycline, and ciprofloxacin were also observed, including a chloramphenicol-resistant strain which has acquired penicillin and ciprofloxacin resistance. CONCLUSIONS: This study suggests that chloramphenicol-resistant N. meningitidis is more widespread than previously thought, and that the previously-identified resistant lineage is now found in multiple countries in Southeast Asia.

Prophylactic amoxicillin for the prevention of meningococcal infection in infants with atypical hemolytic uremic syndrome under treatment with eculizumab: a report of two cases.

Eculizumab, a humanized monoclonal antibody to complement C5, is a therapeutic drug for atypical hemolytic-uremic syndrome (aHUS) that inhibits the terminal pathway of complement. Patients on eculizumab therapy may become more susceptible to infection with capsule-forming bacteria, including meningococci. Therefore, meningococcal vaccination is required for patients who are on eculizumab therapy. However, the means to prevent meningococcal infection in infants who cannot be vaccinated with the available meningococcal vaccine have not yet been established internationally. In two infants with aHUS at 4-5 months after birth, prophylactic oral amoxicillin was administered, and meningococcal infection was not detected during the period between the initiation of eculizumab therapy and the administration of meningococcal vaccine. Neither adverse events related to amoxicillin nor thrombotic microangiopathy occurred during the treatment. Thus, oral administration of amoxicillin may be effective for preventing meningococcal infection under treatment with eculizumab in infants who have not received meningococcal vaccination.

Australian Meningococcal Surveillance Programme annual report, 2018.

Invasive meningococcal disease (IMD) is a notifiable disease in Australia, and both probable and laboratory-confirmed cases of IMD are reported to the National Notifiable Diseases Surveillance System (NNDSS). In 2018, there were 281 IMD cases notified to the NNDSS. Of these, 278 were laboratory-confirmed cases analysed by the reference laboratories of the Australian National Neisseria Network (NNN). On investigation, the serogroup was able to be determined for 98.6% (274/278) of laboratory-confirmed cases. Serogroup B infections accounted for 44.2% of cases (123 cases); serogroup W for 36.3% of cases (101 cases); serogroup Y infections for 15.8% (44 cases) and serogroup C 1.4% (4 cases); and there were two unrelated cases (0.7%) of IMD attributable to serogroup E. Using molecular methods, 181/278 IMD cases were able to be typed. Of note was that 89% of typed serogroup W IMD cases (66/74) were porA antigen type P1.5,2; of this number, 44% (29/66) were sequence type 11, the hypervirulent strain reported in recent outbreaks in Australia and overseas. The primary age peak of IMD in Australia in 2018 was again observed in adults aged 45 years or more; a secondary disease peak was observed in children and infants aged less than 5 years. Serogroup B infections predominated in those aged less than 5 years, whereas serogroup W and serogroup Y infections predominated in those aged 45 years or more. Of the IMD isolates tested for antimicrobial susceptibility, 1.4% (3/210) were resistant to penicillin with an MIC ≥ 1 mg/L, and decreased susceptibility to penicillin was observed in a further 93.8% (197/210) of isolates. All isolates were susceptible to ceftriaxone and rifampicin; there was one isolate less susceptible to ciprofloxacin.

Neisseria meningitidis with H552Y substitution on rpoB gene shows attenuated behavior in vivo: report of a rifampicin-resistant case following chemoprophylaxis.

We present the first Italian reported case of an invasive meningococcal disease with rifampicin-resistance (Rif-R)secondary to chemoprophylaxis. The case is entered in a cluster of two IMDs registered in Tuscany, Italy, in November 2019 caused by two non-differentiable group-C Neisseria meningitidis belonging to ST-11 clonal-complex. The contact case, differently from the index, harbored H552Y mutation on rpoB gene which is known to confer Rif-R putting a high-cost fee on bacterial fitness. The extremely mild clinical presentation in the contact can constitute an in vivo demonstration of the virulence attenuation observed in vitro for H552Ymutants. Clinicians should be aware of the possibility of secondary cases with induced Rif-R and keep a high level of suspicion on contacts who received rifampicin-chemoprophylaxis. Molecular characterization of Rif-R should be performed routinely directly on biological samples and not only on isolates, in order to rapidly detect rare cases of resistance and consequently modify chemoprophylaxis for contacts.

[Neisseria meningitidis isolated from patients in men who have sex with men]. / Neisseria meningitidis aislada de muestras de hombres que tienen sexo con hombres.

During the periods 2000-2004 and 2014-2015, Neisseria meningitidis was investigated in men who have sex with men, 1143 and 544 respectively, who consulted in the sexually-transmitted disease program. Prevalence, serogroup distribution and susceptibility to antibiotics were determined. Pharyngeal, rectal and urethral swabs were cultivated on selective Thayer-Martin modified medium. The identification was performed by biochemical tests and mass spectrometry by MALDI-TOF. Serogroups B, C, W and Y were investigated by PCR in 85 isolates recovered from the pharynx belonging to the second period. MICs of penicillin, ceftriaxone, rifampicin, azithromycin and ciprofloxacin were determined for 66 and 102 isolates from periods 1 and 2 respectively, according to CLSI. The prevalence of N. meningitidis was 17.8% and 28.1%, in periods 1 and 2 respectively; the isolates were mainly recovered from the pharynx. The distribution of serogroups was B 31.5%; Y 7.6%; W 3.3% and 9.8% non-capsulated and the rest would belong to other serogroups. Isolates classified as intermediate to penicillin were 34.8% and 63.7% (first and second periods, respectively); moreover, 11.8% of the isolates from the second period were resistant. All isolates were susceptible to ceftriaxone, to ciprofloxacin (except 3 isolates with MIC values between 0.25 and 0.5µg/ml), 3% were resistant to rifampicin and 2% were not susceptible to azithromicin. The prevalence of N. meningitidis carriage in men who have sex with men was high with a high rate of penicillin non-susceptible isolates. B was the prevalent serogroup.

Failure of first meningococcal vaccination in patients with atypical haemolytic uraemic syndrome treated with eculizumab.

BACKGROUND: The C5 complement inhibitor eculizumab is a first-line treatment in atypical haemolytic uraemic syndrome (aHUS). Therapy with eculizumab is associated with a highly increased risk for meningococcal infection. Therefore, vaccination is highly recommended before beginning treatment. Efficacy of quadrivalent meningococcal vaccines (MenACWY) in patients treated with the C5 complement inhibitor eculizumab in aHUS has not yet been determined. METHODS: Patients with aHUS received one dose of a MenACWY conjugate vaccine before eculizumab treatment commenced. Bactericidal titres against meningococcal serogroups A, C, W and Y were determined using baby rabbit complement in 25 patients. RESULTS: Full immune response to meningococcal vaccination was detected in five patients (20%), while seven patients (28%) showed no immune response in any of the tested serogroups. The remaining 13 patients showed incomplete immune response with proof of protective antibody titres for one to three serogroups without perceptible preference for any serogroup. Bactericidal titres after re-vaccination were available for 17 patients. Nine patients with incomplete immune response after first vaccinations showed protective antibody titres for all serogroups after re-vaccination. Kidney function had improved in >50% of patients at the time of re-vaccination compared with the time of first vaccination and immunosuppressive therapy was only applied to re-vaccinated patients following kidney transplantation. CONCLUSIONS: Immunogenicity of first quadrivalent meninongococcal vaccination is insufficient in patients with aHUS. Booster response is promising, but incomplete. Therefore, establishing antibiotic prophylaxes seems pivotal.