Emerging Resistance in Neisseria meningitidis and Neisseria gonorrhoeae

Paola Stefanelli

Disclosures

Expert Rev Anti Infect Ther. 2011;9(2):237-244. 

In This Article

Abstract and Introduction

Abstract

The value of monitoring antimicrobial resistance is particularly significant for Neisseria meningitidis and Neisseria gonorrhoeae diseases, even if it is for different reasons. Although there is no global alert for the spread of resistant meningococcal strains, the emergence of resistance is correlated to the outcome of treatment and the successful prophylaxis of close contacts. Few cases of resistance among meningococci have been recorded worldwide; it remains unclear what intriguing mechanism is responsible for maintaining resistance in these cases in the absence of significant antibiotic selective pressure, as in the case of penicillin; on the contrary, although rifampicin is the antibiotic of choice in the prophylaxis of close contacts, there is a very low rate of resistance. The emergence of multidrug-resistant N. gonorrhoeae is a great challenge in controlling gonorrhea as one of the main sexually transmitted bacterial diseases. International surveillance programs permit the monitoring of the susceptibility of the pathogen and allow the revision of the standardized treatment regimen when the situation changes.

Introduction

Resistance becomes a clinical problem when the frequency of the resistant variant threatens the effectiveness of empirical drug therapy. The global rise of antimicrobial resistance (AMR) in bacteria combined with the decreasing number of innovative antibacterial agents has led to warnings that we may soon lose our ability to treat bacterial infections.[1] The cost of resistance is one of the most important factors determining both the rate and extent of resistance emergence with an impact on public health management.[2,3] Antibiotic-resistant infections can double the duration of hospital stay, double mortality and probably double morbidity compared with drug-susceptible infections as described for the first time by Holmberg et al.[4] Over the last 5 years, the practice of clinical microbiology and infectious diseases has focused more and more on the problem of antimicrobial resistance. The burden of antibiotic resistance has been estimated in several studies and reviews.[5–7] In this context, antimicrobial surveillance systems constitute the main tool in estimating the rate of resistant pathogens worldwide. Routine antimicrobial surveillance is invaluable for nations, regions and local facilities, because it is essential to ensure accurate information in order to establish and modify treatment guidelines and to aid in the prescription of appropriate empirical antimicrobial therapy.

Several mechanisms have evolved that confer antibiotic resistance to bacteria. These mechanisms can either chemically modify the antibiotic, render it inactive through physical removal from the cell, or modify the target site so that it is not recognized by the antibiotic.

The most common mode is enzymatic inactivation of the antibiotic. An existing cellular enzyme is modified to react with the antibiotic in such a way that it no longer affects the microorganism. An alternative strategy utilized by many bacteria is the alteration of the antibiotic target site. Generally speaking, bacteria are able to acquire resistance to antimicrobials to adapt themselves to the new conditions and, in the absence of mobile elements (which generally mediate high-level resistance), a step-wise progression from low-level to high-level resistance occurs through sequential single point mutations in the chromosome. Several mechanisms are developed by bacteria in order to acquire resistance to antibiotics. All require either the modification of existing genetic material or the acquisition of new genetic material from another source. This applies also to the two pathogenic Neisseriae species: Neisseria meningitidis and Neisseria gonorrhoeae.

Neisseria meningitidis (meningococcus) and N. gonorrhoeae (gonococcus), the well-known agents of epidemic meningitis and gonorrhea, respectively, are Gram-negative bacteria that specifically infect humans; both pathogens prefer to inhabit distinct human mucosal niches and cause markedly different diseases. Both are able to naturally acquire exogenous DNA or mobile elements and, for these reasons, they are interesting areas of study on the development and spread of antibiotic resistance.

The scope of this article is to review and discuss the current situation and why antibiotic resistance for both the Neisseria pathogens can be considered, for different reasons, an emerging problem.

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