Neisseria gonorrhoeae is evolving into a superbug with resistance to previously and currently recommended antimicrobials for treatment of gonorrhea, which is a major public health concern globally. Given the global nature of gonorrhea, the high rate of usage of antimicrobials, suboptimal control and monitoring of antimicrobial resistance (AMR) and treatment failures, slow update of treatment guidelines in most geographical settings, and the extraordinary capacity of the gonococci to develop and retain AMR, it is likely that the global problem of gonococcal AMR will worsen in the foreseeable future and that the severe complications of gonorrhea will emerge as a silent epidemic. By understanding the evolution, emergence, and spread of AMR in N. gonorrhoeae, including its molecular and phenotypic mechanisms, resistance to antimicrobials used clinically can be anticipated, future methods for genetic testing for AMR might permit region-specific and tailor-made antimicrobial therapy, and the design of novel antimicrobials to circumvent the resistance problems can be undertaken more rationally. This review focuses on the history and evolution of gonorrhea treatment regimens and emerging resistance to them, on genetic and phenotypic determinants of gonococcal resistance to previously and currently recommended antimicrobials, including biological costs or benefits; and on crucial actions and future advances necessary to detect and treat resistant gonococcal strains and, ultimately, retain gonorrhea as a treatable infection.

Antimicrobial Resistance in Neisseria gonorrhoeae in the 21st Century: Past, Evolution, and Future

Pathogenesis of human immunodeficiency virus infection.

In 1990 it was estimated that 4123 million of the world's 5267 million population—78%—lived in developing countries. Of the 39.5 million deaths in the developing world, 9.2 million were estimated to have been caused by infectious and parasitic disease; infections of the lower respiratory tract were the third most common cause of death worldwide, and diarrhoeal diseases were the fourth.1 Ninety eight per cent of deaths in children occur in the developing world, mostly as a result of infections.

Projections of disability adjusted life years (that is, the years of life without disability) for the year 2020 show great improvement in developing regions: people are living longer without disabilities.2 However, even the most pessimistic model analysed did not take into account the possibility that the development of new antimicrobial drugs might slow or cease, and that rates of drug resistance in bacteria such as pneumococci, Mycobacterium tuberculosis , or Staphylococcus aureus might increase. We chart the progress and impact of bacterial resistance to antimicrobial drugs in the developing world. The information in this review has been assembled from searches of the computerised databases Medline and Bath Information and Data Services, discussions with colleagues, and personal knowledge.

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Although even the most potent and recently developed antimicrobial drugs are available throughout the world, …

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Antimicrobial resistance in developing countries.

ANTIGENIC SIMILARITIES BETWEEN BRAIN COMPONENTS AND BACTERIA CAUSING MENINGITIS: Implications for Vaccine Development and Pathogenesis

Type IV pili are remarkably strong, flexible filaments with varied roles in bacterial pathogenicity. All Gram-negative bacterial surfaces have type IV pili, which are polymeric assemblies of the protein pilin that evoke the host immune response and are potential drug and vaccine targets. Pilin structures that have been solved using X-ray crystallography and nuclear magnetic resonance, together with models for pilus architectures inferred from electron microscopy, fibre diffraction and computation, have established a molecular basis for assembly and multi-functionality, with implications for therapeutic interventions.

Type IV pilus structure and bacterial pathogenicity

Immunologic Response of Man to Group B Meningococcal Polysaccharide Vaccines

Background. Despite multiple antiviral humoral and cellular immune responses, infection with the human immunodeficiency virus (HIV) results in a progressively debilitating disease. We hypothesized that a more effective immune response could be generated by postinfection vaccination with HIV-specific antigens. Methods. We performed a phase I trial of the safety and immunogenicity of a vaccine prepared from molecularly cloned envelope protein, gp160, in 30 volunteer subjects with HIV infection in Walter Reed stage 1 or 2. The vaccine was administered either on days 0, 30, and 120 or on days 0, 30, 60, 120, 150, and 180. HIV-specific humoral and cellular immune responses were measured; local and systemic reactions to vaccination, including general measures of immune function, were monitored. Results. In 19 of the 30 subjects both humoral and cellular immunity to HIV envelope proteins increased in response to vaccination with gp160. Seroconversion to selected envelope epitopes was observed, as were new T-cell...

https://www.nejm.org/doi/pdf/10.1056/NEJM199106133242401

A Phase I Evaluation of the Safety and Immunogenicity of Vaccination with Recombinant gp160 in Patients with Early Human Immunodeficiency Virus Infection

Efficacy trial of a parenteral gonococcal pilus vaccine in men

Because of the high prevalence of penicillinase-producing Neisseria gonorrhoeae in the Republic of Korea, spectinomycin has been used there in the primary treatment of gonococcal infections in U.S. military personnel since 1981, but there have been increasingly frequent reports of treatment failures with spectinomycin. We conducted a clinical study to determine the efficacy of spectinomycin treatment in 124 U.S. servicemen in the Republic of Korea who had urethral gonococcal infections. Ninety-seven patients were treated with spectinomycin alone and evaluated in a follow-up visit. In eight patients (8.2 percent), this treatment was unsuccessful. Antibiotic-sensitivity testing on isolates from seven of the patients with treatment failure demonstrated that six isolates were highly resistant to spectinomycin (minimal inhibitory concentration, greater than or equal to 100 micrograms per milliliter). None of the spectinomycin-resistant strains had become resistant to penicillin, either through the production of penicillinase or through a chromosomal mutation. Although the mechanism of spectinomycin resistance appears to be a chromosomal mutation, these isolates were generally sensitive to other antibiotics. The prevalence of resistance to spectinomycin resulted in the substitution of ceftriaxone for the primary treatment of gonorrhea acquired by U.S. military personnel in the Republic of Korea. We believe that the rapid emergence of spectinomycin resistance in this population mandates a cautious approach to widescale use of the drug and indicates a need to broaden current surveillance programs.

Effect of spectinomycin use on the prevalence of spectinomycin-resistant and of penicillinase-producing Neisseria gonorrhoeae.

IT is difficult for those of us practicing modern-day medicine to comprehend how pervasive syphilis was in the pre-antibiotic era. For example, medical textbooks commonly divided the discussion of organ systems into sections on congenital defects, tumors, trauma, and infections, but listed syphilis as a separate category. Sir William Osier was often quoted: "Know syphilis in all its manifestations and relations, and all other things clinical will be added unto you." All that has changed. No disease was more dramatically affected by antibiotics than syphilis. The incidence fell 18-fold from a peak of 72 cases per 100,000 population in 1943 . . .

Edmund C. Tramont

Papers

Immunologic Response of Man to Group B Meningococcal Polysaccharide Vaccines

A Phase I Evaluation of the Safety and Immunogenicity of Vaccination with Recombinant gp160 in Patients with Early Human Immunodeficiency Virus Infection

Efficacy trial of a parenteral gonococcal pilus vaccine in men

Effect of spectinomycin use on the prevalence of spectinomycin-resistant and of penicillinase-producing Neisseria gonorrhoeae.

Syphilis in the AIDS era.