Comparative study of gonococcal susceptibility to penicillin in the United States, 1955-1969.
01 Nov 1970-The Journal of Infectious Diseases (Oxford University Press)-Vol. 122, Iss: 5, pp 459-461
TL;DR: Although the Public Health Service recommends penicillin as the antibiotic of choice in the treatment of this disease, experts throughout the world generally agree that resistance of Neisseria gonorrhoeae toPenicillin has developed and is continuing to develop.
Abstract: The incidence of gonorrhea continues to rise at an alarming rate. In 1969, the increase was about 13 96, and an estimated minimum of 1,680,000 cases of the disease will occur in the United States in 1970. Thus, gonorrhea continues to be the number one reported bacterial infection in adults. Although the Public Health Service recommends penicillin as the antibiotic of choice in the treatment of this disease, experts throughout the world generally agree that resistance of Neisseria gonorrhoeae to penicillin has developed and is continuing to develop. In 1954, 11 years after the advent of penicillin in the treatment of gonorrhea, in-vitro studies by Love and Finland [1] demonstrated that all of the 106 cultures of gonococci tested were inhibited by 0.06 units/ml or less of penicillin. Two years later, Thayer et al. [2] reported that 22 96 of the gonococcal isolates tested required 0.2 units/ml of penicillin for complete inhibition. Reyn [3] in 1963, after studying susceptibility of the gonococcus to antibiotics in Denmark, stated that 56 96 of the routine cultures were less sensitive to penicillin than those isolated in 1944.
Citations
More filters
TL;DR: 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, and future methods for genetic testing for AMR might permit region-specific and tailor-made antimicrobial therapy, the design of novel antimicroBials to circumvent the resistance problems can be undertaken more rationally.
Abstract: 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.
840 citations
TL;DR: The recent marked increase in incidence of gonorrhea prompted this analysis of the systemic manifestations of gonococcal infection, and of 42 patients with disseminated infection, 79% were women.
Abstract: The recent marked increase in incidence of gonorrhea prompted this analysis of the systemic manifestations of gonococcal infection. Of 42 patients with disseminated infection, 79% were wom...
350 citations
TL;DR: The history of gonorrhea treatment regimens and gonococcal resistance to antibiotics, the mechanisms of resistance, resistance monitoring schemes that exist in different international settings, global responses to the challenge of resistance and prospects for future treatment regimen in the 21st century are reviewed.
Abstract: Neisseria gonorrhoeae is a strictly human pathogen that is typically transmitted by sexual contact. The associated disease gonorrhea has plagued humankind for thousands of years, with a current estimated incidence of 78 million cases per year. Advances in antimicrobial discovery in the 1920s and 1930s leading to the discovery of sulfonamides and penicillin begun the era of effective antimicrobial treatment of gonorrhea. Unfortunately, the gonococcus developed decreased susceptibility or even resistance to these initially employed antibiotics, a trend that continued over subsequent decades with each new antibiotic that was brought into clinical practice. As this pattern of resistance has continued into the 21st century, there is now reason for great concern, especially in an era when few new antibiotics have prospects for use as treatment of gonorrhea. Here, we review the history of gonorrhea treatment regimens and gonococcal resistance to antibiotics, the mechanisms of resistance, resistance monitoring schemes that exist in different international settings, global responses to the challenge of resistance, and prospects for future treatment regimens in the 21st century.
187 citations
TL;DR: This work examined cephalosporin MIC trends for Neisseria gonorrhoeae in the UK and undertook pharmacodynamic analyses to predict efficacy against strains with raised MICs and predicted that failures with the standard 400 mg cefixime po and 250 mg ceftriaxone im regimens become likely around the present MIC maxima.
Abstract: BACKGROUND: Gonorrhoea has been among the easiest infections to cure with antibiotics. Nevertheless, emerging resistance has driven repeated treatment shifts. Decreased cephalosporin susceptibility is now being reported. We examined cephalosporin MIC trends for Neisseria gonorrhoeae in the UK and undertook pharmacodynamic analyses to predict efficacy against strains with raised MICs. METHODS: Neisseria gonorrhoeae isolates were collected annually in a structured surveillance from 26 genitourinary medicine clinics in England and Wales. MICs were determined by agar dilution and confirmed by Etests. Pharmacodynamic modelling was performed for cefixime and ceftriaxone with Monte Carlo simulations. RESULTS: There was a progressive emergence of small numbers of gonococci with cephalosporin MICs of 0.125-0.25 mg/L; these were not seen before 2005 but, for ceftriaxone and cefixime, respectively, accounted for 0.4% (95% confidence interval 0.2%-1.1%) and 2.8% (1.6%-4.8%) of the 1253 isolates collected in 2008; such MICs are 16-64 times the modal values for the species. Pharmacodynamic analysis was complicated by evidence that cephalosporins need a longer period with the free drug level above MIC than the 7-10 h required for penicillin G; nevertheless, pharmacodynamic analyses predict that failures with the standard 400 mg cefixime po and 250 mg ceftriaxone im regimens become likely around the present MIC maxima. CONCLUSIONS: Gonococci with ceftriaxone and cefixime MICs of 0.125-0.25 mg/L are accumulating in the UK. These MICs lie on the edge of likely responsiveness to current regimens, which need review. Possible responses include: (i) higher cephalosporin doses; (ii) multidose cephalosporin regimens; (iii) multidrug regimens; (iv) microbiologically directed treatment; or, in the future, (v) drug cycling. The practicalities of these approaches are discussed.
161 citations
TL;DR: To delay the emergence of extensively drug-resistant gonorrhoea, public health systems require strengthening and novel strategies need implementing to enhance the therapeutic lifespan of the few antimicrobial agents that the authors have left.
Abstract: Since the introduction of antibiotics in the 1930s, Neisseria gonorrhoeae has exhibited a remarkable ability to acquire novel genetic resistance determinants. Initially, sulphonamides were replaced by penicillin, while tetracyclines were prescribed for penicillin-allergic patients. With the advent of penicillinase-producing gonococci, spectinomycin was only briefly useful as alternative treatment and plasmid-mediated tetracycline resistance spread rapidly from the mid-1980s onwards. The fluoroquinolones followed but chromosomally mediated resistance appeared after only a decade of use. Seventy years on, we now face a global public health challenge of immense significance—the emergence of resistance to cephalosporins. With lack of investment in the search for new anti-gonococcal antimicrobial agents or vaccine research, the global spread of multiresistant gonococci can be seen. The impact of untreatable gonorrhoea on HIV transmission could be enormous in high-prevalence countries. This threat comes at a time when many national STI control programmes are weak. To delay the emergence of extensively drug-resistant gonorrhoea, public health systems require strengthening and novel strategies need implementing to enhance the therapeutic lifespan of the few antimicrobial agents that we have left.
160 citations
References
More filters
57 citations
"Comparative study of gonococcal sus..." refers methods in this paper
...gonorrhoeae grown on Thayer-Martin (TM) [5] selective medium were transferred to a TM slant, incubated, and mailed to the Venereal Disease Research Laboratory....
[...]
TL;DR: Successful attempts to demonstrate penicillin-resistant strains of gonococci in cases of failures ofPenicillin treatment have generally failed, and the rare reports of the isolation of such peniillin- resistant strains * have been dis- counted by other observers.
Abstract: FOLLOWING the introduction and extensive use of sulfonamide drugs in the treatment of gonorrhea, increasing proportions of treatment failures from the use of these drugs were encountered.* Such treatment failures could be correlated with increased tolerance in vitro to sulfonamides by the strains isolated from the patients who responded poorly to sulfonamide therapy.† Fortunately, both sulfonamide-sensitive and sulfonamide-resistant strains of gonococci were found to be highly and equally susceptible in vitro to penicillin,‡ and infections with strains of both varieties responded equally well to treatment with this antibiotic.§ Increased tolerance to sulfonamides ∥ and to penicillin¶ could be induced by prolonged and repeated exposures of originally sensitive strains of gonococci in vitro. However, attempts to demonstrate penicillin-resistant strains of gonococci in cases of failures of penicillin treatment have generally failed,# and the rare reports of the isolation of such penicillin-resistant strains * have been dis- counted by other observers, who consider
24 citations
Journal Article•
17 citations
7 citations
Additional excerpts
...05 unit/ml to inhibit their growth [6]....
[...]
Journal Article•
5 citations