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1.  Urinary tract infections treated with single dose of short-acting sulphonamide. 
British Medical Journal  1979;1(6172):1175-1176.
In a prospective study 29 patients with urinary tract infections caused by sulphonamide-sensitive organisms were treated with a single oral dose of the short-acting sulphonamide sulphafurazole. Twenty-seven (93%) of the 29 patients--and possibly all 29--were cured of their infections. There was no difference in the recurrence rates after single-dose treatment and treatment for 10 days or more. Six out of eight strains of Escherichia coli causing early recurrences were sensitive to sulphonamides. These results suggest that uncomplicated infections may safely and successfully be treated by a single oral dose of a short-acting sulphonamide.
PMCID: PMC1599338  PMID: 444997
2.  The novel toluidine sulphonamide EL102 shows pre-clinical in vitro and in vivo activity against prostate cancer and circumvents MDR1 resistance 
British Journal of Cancer  2013;109(8):2131-2141.
Background:
Taxanes are routinely used for the treatment of prostate cancer, however the majority of patients eventually develop resistance. We investigated the potential efficacy of EL102, a novel toluidine sulphonamide, in pre-clinical models of prostate cancer.
Methods:
The effect of EL102 and/or docetaxel on PC-3, DU145, 22Rv1 and CWR22 prostate cancer cells was assessed using cell viability, cell cycle analysis and PARP cleavage assays. Tubulin polymerisation and immunofluorescence assays were used to assess tubulin dynamics. CWR22 xenograft murine model was used to assess effects on tumour proliferation. Multidrug-resistant lung cancer DLKPA was used to assess EL102 in a MDR1-mediated drug resistance background.
Results:
EL102 has in vitro activity against prostate cancer, characterised by accumulation in G2/M, induction of apoptosis, inhibition of Hif1α, and inhibition of tubulin polymerisation and decreased microtubule stability. In vivo, a combination of EL102 and docetaxel exhibits superior tumour inhibition. The DLKP cell line and multidrug-resistant DLKPA variant (which exhibits 205 to 691-fold greater resistance to docetaxel, paclitaxel, vincristine and doxorubicin) are equally sensitive to EL102.
Conclusion:
EL102 shows potential as both a single agent and within combination regimens for the treatment of prostate cancer, particularly in the chemoresistance setting.
doi:10.1038/bjc.2013.537
PMCID: PMC3798953  PMID: 24052043
prostate cancer; chemotherapeutic; toluidine sulphonamide; taxane; MDR1 drug resistance; Hif1
3.  Sulphonamide resistant commensal Neisseria with alterations in the dihydropteroate synthase can be isolated from carriers not exposed to sulphonamides 
BMC Microbiology  2002;2:34.
Background
Development of sulphonamide resistance in Neisseria meningitidis has been suggested to involve horizontal DNA-transfer from a commensal Neisseria species. In this study, we isolated commensal Neisseria from throat specimens and examined the isolates with respect to sulphonamide resistance.
Results
Three resistant clones were identified and the resistance phenotype could be explained by amino acid variations in their dihydropteroate synthase, the target molecule for sulphonamides. Some of these variations occurred in positions corresponding to previously detected variations in resistant N. meningitidis.
Conclusions
Sulphonamide resistant commensal Neisseria were isolated from an environment not exposed to sulphonamides, suggesting that resistant Neisseria has become a natural part of the commensal throat flora.
doi:10.1186/1471-2180-2-34
PMCID: PMC138796  PMID: 12435277
4.  Long-term Control of Bacteriuria with Trimethoprim-Sulphonamide 
British Medical Journal  1971;1(5745):377-379.
Long-term antibacterial therapy with the drug combination trimethoprim-sulphonamide has been used for the treatment of 52 patients with persistent or recurrent bacteriuria. Hypersensitivity or gastrointestinal intolerance was observed in six. Bacteriuria was controlled in 36 out of 38 patients with organisms sensitive to trimethoprim-sulphonamide, 28 having received treatment for periods ranging from 6 to 49 months. Treatment was in some cases curative and in others suppressive or prophylactic. The importance of supportive measures is re-emphasized.
PMCID: PMC1795024  PMID: 5541926
5.  Resistant Urinary Infections Resulting from Changes in Resistance Pattern of Faecal Flora Induced by Sulphonamide and Hospital Environment* 
British Medical Journal  1970;3(5718):305-309.
The faecal flora was studied in eight children admitted to hospital for treatment of a first urinary infection with sulphonamides. The original, sulphonamide-sensitive Escherichia coli organisms were found to disappear, to be replaced by other E. coli serotypes that were almost invariably resistant to sulphonamides. Some of these serotypes carried R-factors for multiple antibiotic resistance.
Possibly some urinary infections with antibiotic-resistant organisms may be due to faecal organisms whose resistance has been changed by previous antibiotic treatment. Hence it is important to study the effects of individual antibiotics on the faecal flora.
PMCID: PMC1701508  PMID: 4916195
6.  Sensitivity of Nocardia to trimethoprim and sulphonamides in vitro 
Journal of Clinical Pathology  1970;23(5):423-426.
Studies in vitro of the sensitivity to trimethoprim and sulphonamides of nine strains of N. asteroides, two strains of N. caviae, and one of N. blackwellii are presented. No unequivocal evidence of synergism was found. Despite this, the inclusion of trimethoprim in the drug regime when sulphonamides are used in the treatment of nocardiosis is suggested on empirical grounds.
PMCID: PMC476784  PMID: 5476868
7.  A haematological study of patients receiving long-term treatment with trimethoprim and sulphonamide 
Journal of Clinical Pathology  1970;23(5):392-396.
The haematological effects of long-term treatment for three months with a combination of trimethoprim and sulphamethoxazole were studied in 10 cases of chronic bronchitis. Trimethoprim selectively inhibits dihydrofolate reductase in bacteria but not in man. Only minor effects on folate metabolism were observed in nine cases, causing no clinical concern. Some degree of thrombocytopenia occurred in the tenth case which improved when folinic acid was given.
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PMCID: PMC476778  PMID: 4920413
8.  Synthesis, Characterization, and Biotoxicity of N N⌢ Donor Sulphonamide Imine Silicon(IV) Complexes 
The organosilicon derivatives of 2-[1-(2-furayl)ethyledene]sulphathiazole with organosilicon chlorides have been synthesised and characterized on the basis of analytical, conductance, and spectroscopic techniques. Probable trigonal bipyramidal and octahedral structures for the resulting derivatives have been proposed on the basis of electronic, IR, 1H, 13C NMR, and 29Si NMR spectral studies. In the search for better fungicides, bactericides, nematicides, and insecticides studies were conducted to assess the growth-inhibiting potential of the synthesized complexes against various pathogenic fungal, bacterial strains, root-knot nematode Meloidogyne incognita, and insect Trogoderma granarium. These studies demonstrate that the concentrations reached levels which are sufficient to inhibit and kill the pathogens, nematode, and insect.
doi:10.1155/BCA/2006/13743
PMCID: PMC1686292  PMID: 17496998
9.  Synergism between sulphonamide drugs and antibiotics of the polymyxin group against Proteus sp. in vitro 
Journal of Clinical Pathology  1963;16(4):362-366.
Interesting synergism in vitro between a recently introduced antibiotic, colistin methane sulphonate, and sulphonamide drugs is described. The observations were extended to polymyxin B sulphate and sulphonamides with essentially similar results. The combinations are bactericidal at therapeutic levels, the ratio of drugs to one another is not critical, and the effect is present over a fairly wide pH range.
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PMCID: PMC480577  PMID: 14044038
10.  Ortho-toluene sulphonamide and saccharin in the promotion of bladder cancer in the rat. 
British Journal of Cancer  1980;42(1):129-147.
The importance of the contaminant OTS in the promoting activity of commercial saccharin on rat bladder neoplasia was investigated. OTS, OTS-free and OTS-contaminated saccharin were administered in the drinking water or diet for 2 years to groups of rats pretreated with an intravesical instillation of MNU; OTS alone and OTS-free saccharin were also given to groups of rats not pretreated with MNU. Administration of OTS was not associated with changes in urinary pH, crystalluria or calculus formation, had no effect on the histology of normal rat bladder, and did not increase the incidence of bladder hyperplasia or neoplasia elicited by pretreatment with MNU. No differences could be found between the effect of OTS-free or OTS-contaminated saccharin on bladders of rats pretreated with MNU. These results indicate that OTS contamination played no part in the reported promoting activity of saccharin on the rat bladder. Administration of saccharin did not increase urinary pH, crystalluria or calculus formation, and failed to promote bladder neoplasia after a carcinogenic dose of MNU, though the numbers of proliferative lesions in the bladder were increased.
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PMCID: PMC2010463  PMID: 7426324
11.  Adverse drug events resulting from use of drugs with sulphonamide-containing anti-malarials and artemisinin-based ingredients: findings on incidence and household costs from three districts with routine demographic surveillance systems in rural Tanzania 
Malaria Journal  2013;12:236.
Background
Anti-malarial regimens containing sulphonamide or artemisinin ingredients are widely used in malaria-endemic countries. However, evidence of the incidence of adverse drug reactions (ADR) to these drugs is limited, especially in Africa, and there is a complete absence of information on the economic burden such ADR place on patients. This study aimed to document ADR incidence and associated household costs in three high malaria transmission districts in rural Tanzania covered by demographic surveillance systems.
Methods
Active and passive surveillance methods were used to identify ADR from sulphadoxine-pyrimethamine (SP) and artemisinin (AS) use. ADR were identified by trained clinicians at health facilities (passive surveillance) and through cross-sectional household surveys (active surveillance). Potential cases were followed up at home, where a complete history and physical examination was undertaken, and household cost data collected. Patients were classified as having ‘possible’ or ‘probable’ ADR by a physician.
Results
A total of 95 suspected ADR were identified during a two-year period, of which 79 were traced, and 67 reported use of SP and/or AS prior to ADR onset. Thirty-four cases were classified as ‘probable’ and 33 as ‘possible’ ADRs. Most (53) cases were associated with SP monotherapy, 13 with the AS/SP combination (available in one of the two areas only), and one with AS monotherapy. Annual ADR incidence per 100,000 exposures was estimated based on ‘probable’ ADR only at 5.6 for AS/SP in combination, and 25.0 and 11.6 for SP monotherapy. Median ADR treatment costs per episode ranged from US$2.23 for those making a single provider visit to US$146.93 for patients with four visits. Seventy-three per cent of patients used out-of-pocket funds or sold part of their farm harvests to pay for treatment, and 19% borrowed money.
Conclusion
Both passive and active surveillance methods proved feasible methods for anti-malarial ADR surveillance, with active surveillance being an important complement to facility-based surveillance, given the widespread practice of self-medication. Household costs associated with ADR treatment were high and potentially catastrophic. Efforts should be made to both improve pharmacovigilance across Africa and to identify strategies to reduce the economic burden endured by households suffering from ADR.
doi:10.1186/1475-2875-12-236
PMCID: PMC3710484  PMID: 23844934
Anti-malarial; Adverse drug reactions; Household costs; ACT; Sulphonamide; Tanzania
12.  A novel phenoxy thiophene sulphonamide molecule protects against glutamate evoked oxidative injury in a neuronal cell model 
BMC Neuroscience  2013;14:93.
Background
Glutamate is one of the major neurotransmitters in the central nervous system. It is a potent neurotoxin capable of neuronal destruction through numerous signal pathways when present in high concentration. Glutamate-evoked excitotoxicity has been implicated in the etiology of many neurodegenerative diseases including Alzheimer’s disease (AD), Parkinson’s disease (PD), and ischemic stroke. Increasing evidence has shown that reactive oxygen species (ROS) provoked by glutamate-linked oxidative stress plays a crucial role in the pathogenesis of these disorders. We previously reported the discovery of an aryl thiophene compound, 4-chloro-N-(naphthalen-1-ylmethyl)-5-(3-(piperazin-1-yl)phenoxy)thiophene-2-sulfonamide (B355252) from a proprietary library of small molecules. We showed that this compound was capable of potentiating nerve growth factor (NGF)-primed neurite outgrowth in neuronal cell models in a low NGF environment. In the present study we investigated the neuroprotective effects and signaling pathways of B355252 on glutamate-evoked excitotoxicity in HT-22, a murine hippocampal neuronal cell line.
Results
Glutamate significantly decreased HT-22 neuronal cell viability in a concentration-dependent manner as measured by the MTT assay. Co-treatment with 2, 4, and 8 μM B355252 protected against cell death caused by glutamate-induced toxicity by 9.1% (p<0.01), 26.0% (p<0.001), and 61.9% (p<0.001) respectively, compared to glutamate-treated control group. B355252 at a concentration of 8 μM fully rescued HT-22 from the neurototoxic effects of glutamate, and by itself increased cell viability by 16% (p<0.001) above untreated control. Glutamate enhanced reduction in glutathione (GSH) synthesis was reversed by 15% (p<0.01) in the presence of B355252. B355252 reduced the expression of apoptosis inducing factor (AIF) by 27%, while the proapoptotic Bcl-2 associated X protein (Bax) was strongly attenuated 3-fold. Glutamate-evoked increase in intracellular calcium (Ca2+) load and subsequent ROS production was inhibited by 71% (p<0.001) and 40% (p<0.001) respectively, to comparable level as untreated control in the presence of B355252. Glutamate significantly upregulated the phosphorylation of extracellular signal regulated kinase Erk1/2 (pERK1/2), while decreasing Erk3. In contrast, B355252 potently attenuated the glutamate-dependent activation of Erk1/2 and robustly increased the level of ERK3 in HT-22.
Conclusions
A novel phenoxy thiophene small molecule, B355252, suppresses glutamate-evoked oxidative stress in HT-22 neurons by blocking Ca2+ and ROS production, and altering the expression or phosphorylation states of Erk kinases. This molecule previously reported to enhance neurite outgrowth in the presence of sub-physiological concentrations of NGF appears to be a promising drug candidate for development as a potential therapeutic and neuroprotective agent for various neurodegenerative disorders.
doi:10.1186/1471-2202-14-93
PMCID: PMC3846642  PMID: 24004478
Glutamate; Neuroprotection; Excitotoxicity; Small molecule; Alzheimer’s disease; Oxidative stress; ERK3; Neurodegenerative disease; Phenoxy thiophene; HT-22
13.  Pharmacokinetic Determinants of Penicillin Cure of Gonococcal Urethritis 
In a 1964 study of the pharmacokinetic determinants of penicillin cure of gonococcal urethritis, 45 male prisoner volunteers were experimentally infected with strains of Neisseria gonorrhoeae having known in vitro penicillin susceptibility. After developing urethritis, subjects received intramuscular penicillin G and had serum samples obtained serially to determine penicillin concentration. Using a multiple regression technique, we studied patient-associated parameters and parameters of the serum penicillin curves to determine the best predictors of treatment results. Cure was best predicted by the time the serum penicillin concentration remained above three to four times the penicillin minimum inhibitory concentration of the infecting strain (probability of correct classification, >0.80). Those cured had serum penicillin concentrations which remained in this range for means of 7 to 10 h. Our findings confirm principles of antimicrobial therapy derived from animal models and may have application in studying therapy of gonorrhea and other infectious diseases.
PMCID: PMC352715  PMID: 464590
14.  How suitable are available pharmaceuticals for the treatment of sexually transmitted diseases? 1: Conditions presenting as genital discharges 
The relative prevalence of sexually transmitted diseases and the agents available for the treatment of these diseases commonly presenting as genital discharges—namely, gonorrhoea, candidosis, trichomoniasis, and non-specific genital infection—are reviewed. The many agents that are active against gonorrhoea are listed, but none is ideal. Penicillin, in spite of its allergic side effects, has remained the drug of choice for 25 years because it is cheap, easily obtained, lacks toxicity even in pregnancy, and is effective. Its use is now threatened by the emergence of some strains that are able to produce penicillinase. At present the policy is to obtain the best results from penicillin while these are acceptable, but the clinician in some countries is badly served by the availability of procaine penicillin in aqueous suspension. There is a need for an effective penicillin or cephalosporin that is penicillinase resistant and cheap. Cefuroxime offers considerable hope but it is likely to be expensive in the immediate future.
There are many preparations for the local treatment of candidosis. The confidence expressed by the manufacturers in recommending a three-day treatment is, it is hoped, based on a superior product. Nevertheless there is a need for a safe systemically absorbed fungicide which could be used orally, or some substance that could render the vagina an inhospitable environment for the organism.
In the treatment of trichomoniasis the pharmaceutical industry in providing substances more than 90% effective in a single dose has done all that can be expected. Any further advances lie in the field of human behaviour rather than pharmaceutical research.
In the treatment of non-specific genital infection the needs are more of research than of therapy. More knowledge is required of the cause of the condition and the relative role of contending pathogens, and of the results of treatment of patients and contacts in which Chlamydia or other suspect pathogens have been isolated.
PMCID: PMC1045430  PMID: 338125
15.  Susceptibility of N. gonorrhoeae to Antibiotics 
Gonorrhea has increased in incidence over the past five years in Manitoba as elsewhere. Cases which did not respond to routine penicillin treatment were noted to be occuring more often. In 1948, strains of N. gonorrhoeae isolated in Canada were all sensitive to 0.06 unit of penicillin per c.c. in vitro. Commencing in May 1962, strains of N. gonorrhoeae were isolated from 100 patients of each sex attending the clinic at the St. Boniface General Hospital. Eighteen per cent required concentrations of more than 0.05 unit of penicillin per ml. to inhibit growth; 31% were not inhibited by the 2 μg. disc of dihydrostreptomycin; but only one strain was found resistant to sulfisoxazole and none to oxytetracycline. Results of penicillin treatment were markedly less successful in the patients with strains that demonstrated reduced penicillin sensitivity. Use of streptomycin and a sulfonamide proved to be a satisfactory substitute. Intramuscular oxytetracycline was less successful despite the laboratory findings.
PMCID: PMC1921705  PMID: 14063939
16.  One-session treatment of gonorrhoea in males with procaine penicillin plus probenecid* 
Postgraduate Medical Journal  1970;46(533):142-145.
Six hundred and thirteen male patients with acute uncomplicated gonorrhoea have been treated alternately with single injections of 1·2 mega-units of aqueous procaine penicillin alone or with the same dose and preparation of penicillin with an additional 1·0 g of probenecid given orally immediately prior to injection.
Whether the failure rates were assessed on the basis of an absence of further sexual exposure or by classifying all recurrences within 1 or 2 weeks regardless of history as treatment failures the results were significantly better when probenecid was also given.
The use of a single dose of probenecid is thus capable of maintaining the success of single injection procedures for the treatment of gonorrhoea based on procaine penicillin and thus represents a bulwark for the future should the powers of penicillin against the gonococcus in London deteriorate further.
PMCID: PMC2466978  PMID: 5440736
17.  Antimicrobial agents and gonorrhoea: therapeutic choice, resistance and susceptibility testing. 
Genitourinary Medicine  1996;72(4):253-257.
INTRODUCTION: Neisseria gonorrhoeae, the causative agent of gonorrhoea is a particularly well adapted pathogen that has continued to evolve mechanisms to evade treatment with antimicrobial agents. THERAPEUTIC CHOICE: The choice of antibiotic for use in the first-line treatment of gonorrhoea should be made with knowledge of the susceptibility of the isolates of N gonorrhoeae to be encountered. RESISTANCE: High-level resistance to penicillin and tetracycline in N gonorrhoeae is plasmid-mediated and a major therapeutic problem. Penicillinase-producing N gonorrhoeae, first described in 1976, have now spread worldwide and tetracycline-resistant N gonorrhoeae, described in 1985, are becoming increasingly prevalent. Chromosomal resistance to penicillin is low-level and affects a range of antibiotics. High-level resistance to spectinomycin has been sporadic and has not limited its use whereas the emergence of resistance to ciprofloxacin will have a significant impact on its use for gonorrhoea. SUSCEPTIBILITY TESTING: A variety of methods are available including disc diffusion, breakpoint agar dilution technique, E-test and determination of the minimum inhibitory concentration (MIC). The choice of methodology will depend on the number and type of isolates and the facilities available for testing. DISCUSSION: Surveillance programmes to monitor levels of antibiotic resistant isolates are essential to ensure therapeutic success.
PMCID: PMC1195672  PMID: 8976828
18.  Antibiotic susceptibility of Neisseriagonorrhoeae in Arkhangelsk, Russia 
Sexually Transmitted Infections  2007;83(2):133-135.
Objectives
To characterise comprehensively the antibiotic susceptibility of Neisseria gonorrhoeae in Arkhangelsk, Russia, and to investigate whether the recommended treatment guidelines are updated and effective.
Methods
The susceptibility of N gonorrhoeae isolates, cultured during June–November 2004 mainly from consecutive patients with gonorrhoea (n = 76) in Arkhangelsk, to penicillin G, ampicillin, cefixime, ceftriaxone, ciprofloxacin, erythromycin, azithromycin, kanamycin, spectinomycin and tetracycline was analysed using Etest. Nitrocefin discs were used for β‐lactamase detection.
Results
The levels of intermediate susceptibility and resistance to the different antibiotics were as follows: penicillin G 76%, ampicillin 71%, cefixime 0%, ceftriaxone 3%, ciprofloxacin 17%, erythromycin 54%, azithromycin 14%, kanamycin 49%, spectinomycin 0% and tetracycline 92%. Of the isolates 55 (72%) were determined as multiresistant—that is, they showed intermediate susceptibility or resistance to three or more classes of antibiotics. However, none of the isolates were β‐lactamase producing.
Conclusions
In Arkhangelsk, and presumably in many other areas of Russia, penicillins, ciprofloxacin, erythromycin, azithromycin, kanamycin and tetracycline should not be used in the treatment of gonorrhoea if the results of antibiotic susceptibility testing are not available. In Russia, optimised, standardised and quality‐assured antibiotic susceptibility testing needs to be established in many laboratories. Subsequently, continuous local, regional and national surveillance of antibiotic susceptibility is crucial to detect the emergence of new resistance, monitor changing patterns of susceptibility and be able to update treatment recommendations on a regular basis.
doi:10.1136/sti.2006.021857
PMCID: PMC2598625  PMID: 16971401
antibiotic susceptibility; resistance;  N gonorrhoeae ; Arkhangelsk; Russia
19.  A New Sulphonamide (Sulphonamide E.O.S.) 
British Medical Journal  1941;2(4214):503-507.
PMCID: PMC2163057  PMID: 20783899
20.  Epidemiology of penicillin resistant Neisseria gonorrhoeae. 
Genitourinary Medicine  1991;67(4):307-311.
OBJECTIVE--To study the epidemiology of Neisseria gonorrhoeae that exhibit both chromosomal and plasmid-mediated resistance to penicillin. MATERIALS AND METHODS--A total of 1589 strains of N gonorrhoeae isolated from patients attending St Mary's Hospital, London were tested for both their susceptibility to penicillin and for their auxotype and serotype. RESULTS--Of the 940 non-penicillinase producing N gonorrhoeae, 840 were considered penicillin sensitive (MIC less than or equal to 0.5 mg/l) and 100 were chromosomally-mediated resistant N gonorrhoeae (CMRNG), (MIC greater than or equal to 1.0 mg/l). Of the 649 penicillinase producing N gonorrhoeae (PPNG), 429 carried the 4.4 megadalton (MDa) penicillinase encoding plasmid and 220 carried the 3.2 MDa plasmid. CMRNG were predominantly serogroup IB (90%). PPNG with 3.2 MDa plasmid were the only group more often serogroup IA (58%) than IB (42%). Serovar IA-1/2 and requirement for arginine, hypoxanthine and uracil (AHU) were associated with increased susceptibility to penicillin whereas serovar IB-5/7 was associated with decreased susceptibility in nonPPNG. There was a significant difference in the distribution of the IA and IB serovars between PPNG carrying either the 4.4 MDa or 3.2 MDa plasmid. AHU and PAOU requiring strains were not found among PPNG and were uncommon among CMRNG. CONCLUSION--Some clear associations have been found but the pattern among PPNG appears more complex and in most instances could be related to clusters of a single strain over a short time span.
PMCID: PMC1194706  PMID: 1916793
21.  Susceptibilities of Neisseria gonorrhoeae to fluoroquinolones and other antimicrobial agents in Hyogo and Osaka, Japan 
Sexually Transmitted Infections  2004;80(2):105-107.
Objectives: Decreasing susceptibility of Neisseria gonorrhoeae to fluoroquinolones has been reported in several countries. Knowledge of local N gonorrhoeae susceptibilities to various antimicrobials is important for establishing a rational treatment strategy in each region.
Methods: Isolates of N gonorrhoeae from male urethritis patients attending four urological clinics in Hyogo and Osaka prefectures in Japan were collected during 2002. The MICs for nine antimicrobials: penicillin G, tetracycline, cefixime, ceftriaxone, levofloxacin, gatifloxacin, ciprofloxacin, moxifloxacin, and spectinomycin were determined for each isolate. All isolates were also tested for ß lactamase producing profiles.
Results: Among the 87 isolates obtained, only one isolate was revealed to produce ß lactamase. MIC90 values for ciprofloxacin, levofloxacin, gatifloxacin, and moxifloxacin were over 8 µg/ml, over 8 µg/ml, 4 µg/ml, and 2 µg/ml, respectively. The proportion of isolates resistant to fluoroquinolones was over 60% (ciprofloxacin, 70.1%; levofloxacin, 65.5%; gatifloxacin, 70.1%). Chromosomally mediated penicillin and tetracycline resistance was identified in 12.6% and 33.3% of the isolates. MIC90 values for cefixime and ceftriaxone and were 0.5 µg/ml and 0.0063 µg/ml. All isolates were sensitive to ceftriaxone and 90.8% of them were sensitive to cefixime. MIC90 for spectinomycin was 32 µg/ml and all isolates were sensitive to it. Fluoroquinolone resistance correlated significantly with MICs for penicillin G but not tetracycline.
Conclusion: Ceftriaxone and spectinomycin demonstrated lower MICs and so are recommended for N gonorrhoeae. Susceptibilities of N gonorrhoeae should be monitored periodically by region.
doi:10.1136/sti.2003.006908
PMCID: PMC1744816  PMID: 15054169
22.  An insight into the drug resistance profile & mechanism of drug resistance in Neisseria gonorrhoeae 
Among the aetiological agents of treatable sexually transmitted diseases (STDs), Neissseria gonorrhoeae is considered to be most important because of emerging antibiotic resistant strains that compromise the effectiveness of treatment of the disease - gonorrhoea. In most of the developing countries, treatment of gonorrhoea relies mainly on syndromic management rather than the aetiological based therapy. Gonococcal infections are usually treated with single-dose therapy with an agent found to cure > 95 per cent of cases. Unfortunately during the last few decades, N. gonorrhoeae has developed resistance not only to less expensive antimicrobials such as sulphonamides, penicillin and tetracyclines but also to fluoroquinolones. The resistance trend of N. gonorrhoeae towards these antimicrobials can be categorised into pre-quinolone, quinolone and post-quinolone era. Among the antimicrobials available so far, only the third-generation cephalosporins could be safely recommended as first-line therapy for gonorrhoea globally. However, resistance to oral third-generation cephalosporins has also started emerging in some countries. Therefore, it has become imperative to initiate sustained national and international efforts to reduce infection and misuse of antibiotics so as to prevent further emergence and spread of antimicrobial resistance. It is necessary not only to monitor drug resistance and optimise treatment regimens, but also to gain insight into how gonococcus develops drug resistance. Knowledge of mechanism of resistance would help us to devise methods to prevent the occurrence of drug resistance against existing and new drugs. Such studies could also help in finding out new drug targets in N. gonorrhoeae and also a possibility of identification of new drugs for treating gonorrhoea.
PMCID: PMC3237238  PMID: 22089602
Epidemiology; mechanism of drug resistance; Neisseria gonorrhoeae
23.  Cefonicid as Therapy for Uncomplicated Gonococcal Urethritis Caused by Penicillinase-Producing Neisseria gonorrhoeae 
Western Journal of Medicine  1984;140(2):224-226.
Young men with uncomplicated gonococcal urethritis were treated with 1 gram of cefonicid given intramuscularly plus 1 gram of probenecid by mouth. Of 53 evaluable patients, 33 (62%) had penicillinase-producing Neisseria gonorrhoeae. All but one of these patients were cured. All men who had penicillin-sensitive infections were cured. Cefonicid was highly effective in the treatment of both penicillin-sensitive and penicillin-resistant N gonorrhoeae. Other than moderate pain at the site of injection, there were no adverse side effects. Cefonicid can be added to the group of newer cephalosporins that are effective in the treatment of gonococcal urethritis caused by either penicillin-sensitive or penicillin-resistant strains.
PMCID: PMC1021601  PMID: 6428048
24.  Genotyping as a Tool for Antibiotic Resistance Surveillance of Neisseria gonorrhoeae in New Caledonia: Evidence of a Novel Genotype Associated with Reduced Penicillin Susceptibility▿  
Antibiotic resistance in Neisseria gonorrhoeae continues to be a major concern in public health. Resistance of N. gonorrhoeae bacteria to penicillin G is widespread in most developed countries, which has necessitated a change to newer drugs for treatment of gonococcal infections. Recent reports indicate that resistance to these newer drugs is increasing, highlighting the need for accurate therapeutic recommendations. In some countries or communities, however, N. gonorrhoeae isolates are still susceptible to penicillin, so the use of this antibiotic for single-dose treatments of medically under-resourced patients is beneficial. In order to evaluate the adequacy and sustainability of this treatment approach, we explored the presence and prevalence of chromosomally mediated resistance determinants in N. gonorrhoeae isolates collected from 2005 to 2007 in New Caledonia. We developed two new real-time PCR assays targeting the penB and mtrR determinants, to be used together with a previously described duplex assay targeting the penA and ponA determinants. The results of this study provided evidence that neither the most-common mtrR determinants nor the most-resistance-associated penB alleles are currently circulating in New Caledonia, suggesting that penicillin should still be considered a valuable treatment strategy. Additionally, using our genotyping assay, we observed an unexpected penB genotype at a relatively high frequency that was associated with a decreased susceptibility to penicillin (average MIC, 0.15 μg/ml). Sequencing revealed that this genotype corresponded to an A102S mutation in the penB gene. The molecular tools developed in this study can be used successfully for prospective epidemiological monitoring and surveillance of penicillin susceptibility.
doi:10.1128/AAC.00020-08
PMCID: PMC2533457  PMID: 18591264
25.  Enhancing Gonococcal Antimicrobial Resistance Surveillance: a Real-Time PCR Assay for Detection of Penicillinase-Producing Neisseria gonorrhoeae by Use of Noncultured Clinical Samples▿ 
Journal of Clinical Microbiology  2011;49(2):513-518.
With increasing concerns regarding diminishing treatment options for gonorrhea, maintaining the efficacy of currently used treatments and ensuring optimal Neisseria gonorrhoeae antimicrobial resistance surveillance are of the utmost importance. Penicillin is still used to treat gonorrhea in some parts of the world. In this study, we developed and validated a real-time PCR assay for the detection of penicillinase-producing N. gonorrhoeae (PPNG) in noncultured clinical samples with the aim of enhancing penicillin resistance surveillance. The assay (PPNG-PCR2) was designed to be an indirect marker of penicillinase activity, by targeting a region of sequence predicted to be conserved across all N. gonorrhoeae plasmid types harboring the beta-lactamase gene while not specifically targeting the actual beta-lactamase-encoding sequence. The assay was evaluated by using a total of 118 N. gonorrhoeae clinical isolates and 1,194 clinical specimens, including 239 N. gonorrhoeae-positive clinical samples from which N. gonorrhoeae cells were isolated and for which phenotypic penicillinase results are available. Overall, the PPNG-PCR2 assay provided 100% sensitivity and 98.7% specificity compared to bacterial culture results for the detection of PPNG in clinical specimens. PPNG-PCR2 false-positive results, presumably due to cross-reactions with unrelated bacterial species, were observed for up to 1.3% of clinical samples but could be distinguished on the basis of high cycle threshold values. In tandem with phenotypic surveillance, the PPNG-PCR2 assay has the potential to provide enhanced epidemiological surveillance of N. gonorrhoeae penicillin resistance and is of particular relevance to regions where penicillin is still used to treat gonorrhea.
doi:10.1128/JCM.02024-10
PMCID: PMC3043482  PMID: 21159935

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