Treatment failure in meningococcal meningitis

Turner, Paul; Southern, K.W.; Spencer, Nick; Pullen, H.

doi:10.1016/0140-6736(90)90852-v

Cited by 50 publications

(8 citation statements)

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“…Although treatment with penicillin is still effective against these penicillin-intermediate strains, low-dose treatment regimens may fail for cases involving penicillin-resistant isolates (MIC > 0.5 mg/L) ( 11 ). We report recent emergence and clonal expansion of a phylogenetically related cluster of penicillin-resistant MenW:cc11 isolates in Western Australia.…”

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confidence: 99%

Clonal Expansion of New Penicillin-Resistant Clade of Neisseria meningitidis Serogroup W Clonal Complex 11, Australia

Mowlaboccus¹,

Jolley²,

Bray³

et al. 2017

Emerg. Infect. Dis.

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confidence: 99%

Clonal Expansion of New Penicillin-Resistant Clade of Neisseria meningitidis Serogroup W Clonal Complex 11, Australia

Mowlaboccus¹,

Jolley²,

Bray³

et al. 2017

Emerg. Infect. Dis.

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“…In several countries (e.g., the UK, Spain, Australia) less susceptible isolates have become increasingly common [5][6][7], but most isolates would be expected to remain susceptible to appropriate therapeutic doses of penicillin [8]. Treatment failure has been reported rarely [9,10], and the only account of a treatment failure in the UK [9] concerns a patient treated with a low dose of penicillin. However, detailed case studies of children infected with isolates with reduced susceptibility to penicillin suggest that these infections result in higher mortality [11] and, therefore, reduced penicillin sensitivity may be very important clinically.…”

Section: Introductionmentioning

confidence: 99%

Fatal outcome from meningococcal disease – an association with meningococcal phenotype but not with reduced susceptibility to benzylpenicillin

Trotter¹,

Fox²,

Ramsay³

et al. 2002

Journal of Medical Microbiology

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“…Although treatment failures have been described for strains with the highest MICs (20), the severe infections caused by these strains generally resolve favorably using high doses of penicillin G or amoxicillin, which allow bactericidal concentrations to be reached in cerebrospinal fluid (CSF). The effect of beta-lactams is dependent on the time (T) the antibiotic concentration exceeds its MIC for the microorganism (T Ͼ MIC) (9).…”

Section: Discussionmentioning

confidence: 99%

Use of Animal Models To Support Revising Meningococcal Breakpoints of β-Lactams

Belkacem

Hong

Antunes

et al. 2016

Antimicrob Agents Chemother

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Antibiotic susceptibility testing (AST) in Neisseria meningitidis is an important part of the management of invasive meningococcal disease. It defines MICs of antibiotics that are used in treatment and/or prophylaxis and that mainly belong to the beta-lactams. The interpretation of the AST results requires breakpoints to classify the isolates into susceptible, intermediate, or resistant. The resistance to penicillin G is defined by a MIC of >0.25 mg/liter, and that of amoxicillin is defined by a MIC of >1 mg/ liter. We provide data that may support revision of resistance breakpoints for beta-lactams in meningococci. We used experimental intraperitoneal infection in 8-week-old transgenic female mice expressing human transferrin and human factor H. N eisseria meningitidis is a Gram-negative bacterium frequently encountered in the human nasopharynx, but it is also the causative agent of invasive meningococcal disease (IMD) that provokes mainly septicemia and meningitis. Neisseria meningitidis remains susceptible to beta-lactams, the antibiotics of choice in the treatment of IMD (1). Resistance to beta-lactams in meningococci is extremely rare, but reduced susceptibility to penicillin G and to amoxicillin (intermediate isolates; Pen i ) has been described previously. However, neither resistance nor reduced susceptibility to third-generation cephalosporins has been detected so far (2). The proportions of Pen i isolates differ worldwide and are increasing in several countries and can reach Ͼ30% of total meningococcal isolates (3-7).We have previously shown a direct correlation between the polymorphism of the penA gene encoding the penicillin binding protein 2 (PBP2) and the Pen i phenotype. This phenotype seems to result from the reduced affinity of penicillin G and amoxicillin to PBP2 as well as to modification of the peptidoglycan structure in Pen i isolates with increased pentapeptide-containing muropeptides (8). Horizontal interspecies DNA exchanges in the genus Neisseria are suggested to drive the polymorphism of penA (7). Antibiotic susceptibility testing (AST) is mandatory for beta-lactam antibiotics and requires reliable breakpoints to inform decision making in patient treatment.In order to consistently define breakpoints, penA genes from a large collection of isolates were sequenced, and this allowed the linking of wild-type alleles of penA to a low MIC for penicillin G (Ͻ0.125 mg/liter) (7). This defined the epidemiological susceptibility cutoff values for the MIC of penicillin G to be lower than 0.125 mg/liter and that of amoxicillin to be Ͻ0.250 mg/liter(7). It divided the meningococcal population into one part containing isolates harboring wild-type alleles of penA and another part comprising isolates showing highly diverse penA alleles and MICs of Ն0.125 mg/liter and 0.250 mg/liter for penicillin G and amoxicillin, respectively (7). The MIC value of Ͻ0.125 mg/liter was preferred to define the susceptibility to penicillin G as it fulfills the important rule of not splitting wild-type MIC distributions (9)...

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Treatment failure in meningococcal meningitis

Cited by 50 publications

References 4 publications

Clonal Expansion of New Penicillin-Resistant Clade of Neisseria meningitidis Serogroup W Clonal Complex 11, Australia

Clonal Expansion of New Penicillin-Resistant Clade of Neisseria meningitidis Serogroup W Clonal Complex 11, Australia

Fatal outcome from meningococcal disease – an association with meningococcal phenotype but not with reduced susceptibility to benzylpenicillin

Use of Animal Models To Support Revising Meningococcal Breakpoints of β-Lactams

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