Spectinomycin, gentamicin, and routine disc diffusion testing: An alternative for the treatment and monitoring of multidrug-resistant Neisseria gonorrhoeae?

INTRODUCTION: Neisseria gonorrhoeae is a major concern of public health due to its extraordinary capacity to develop and acquire resistance to different antimicrobials used to treat gonorrhoea. Limited treatment options and uncontrolled transmission have raised the need to assess the antimicrobial susceptibility profile of the isolates and to establish affordable alternatives for laboratory diagnosis. OBJECTIVES: This study aimed to (i) determine the susceptibility profile of 336 clinical isolates of N. gonorrhoeae to ceftriaxone, azithromycin, ciprofloxacin, spectinomycin and gentamicin by the gold standard agar dilution method; (ii) assess the agreement among agar dilution and disc diffusion results for ciprofloxacin, azithromycin, ceftriaxone, spectinomycin and gentamicin. RESULTS: All isolates were susceptible to ceftriaxone and spectinomycin. The levels of resistance to azithromycin and ciprofloxacin were 3.9% and 35.1%, respectively. Intermediate susceptibility to gentamicin was observed in 19.4% of isolates. There was 100% agreement between methods for spectinomycin and ceftriaxone, 99.7% for ciprofloxacin, and 85.7% for azithromycin. For gentamicin, there was 86.3% agreement between agar dilution and disc diffusion, resulting in intermediate susceptible by one method and susceptible by the other method, defined as minor errors. The discordance among agar dilution and disc diffusion results is acceptable for ciprofloxacin, ceftriaxone and spectinomycin as per CLSI M23-Ed4. CONCLUSIONS: Spectinomycin and gentamicin can be considered in some cases as options for the treatment of gonorrhoea in Brazil. Disc diffusion can be an alternative method in routine testing with comparable accuracy to agar dilution.

Gentamicin Susceptibility in Neisseria gonorrhoeae and Treatment Outcomes for Urogenital Gonorrhea After 25 Years of Sustained Gentamicin Use in Malawi.

BACKGROUND: Gentamicin has been used for the treatment of gonorrhea in Malawi since 1993. However, declining clinical cure rates have been suspected. We evaluated current Neisseria gonorrhoeae susceptibility to gentamicin in vitro and clinically. METHODS: Men with acute urethritis were recruited at the Bwaila District Hospital STI Clinic in Lilongwe, Malawi, between January 2017 and August 2019. All men provided urethral swabs for etiological testing at enrollment and test of cure (TOC), 1 week later, using Gram-stained microscopy and culture. We used Etest to determine minimum inhibitory concentrations (MICs) of gentamicin, azithromycin, cefixime, ceftriaxone, ciprofloxacin, and spectinomycin; disc diffusion for tetracycline susceptibility; and whole-genome sequencing (WGS) to verify/refute treatment failure. RESULTS: Among 183 N. gonorrhoeae culture-positive men enrolled, 151 (82.5%) had a swab taken for TOC. Of these 151 men, 16 (10.6%) had a positive culture at TOC. One hundred forty-one baseline isolates were tested for gentamicin susceptibility using Etest: 2 (1.4%), MIC = 2 µg/mL; 111 (78.7%), MIC = 4 µg/mL; and 28 (19.9%), MIC = 8 µg/mL. All isolates were susceptible to azithromycin, cefixime, ceftriaxone, and spectinomycin, whereas 63.1% had intermediate susceptibility or resistance to ciprofloxacin. Almost all (96.1%) isolates were resistant to tetracycline. All examined isolates cultured at TOC (n = 13) had gentamicin MICs ≤8 µg/mL. Ten men had pretreatment and posttreatment isolates examined by whole-genome sequencing; 2 (20%) were verified new infections (4119 and 1272 single-nucleotide polymorphisms), whereas 8 (80%) were confirmed treatment failures (0-1 single-nucleotide polymorphism). CONCLUSIONS: Gentamicin MICs poorly predict gonorrhea treatment outcome with gentamicin, and treatment failures are verified with gonococcal strains with in vitro susceptibility to gentamicin. The first-line treatment of gonorrhea in Malawi should be reassessed.

Dynamic time-kill curve characterization of spectinamide antibiotics 1445 and 1599 for the treatment of tuberculosis.

Spectinamides are a novel class of antibiotics under development for the treatment of MDR- and XDR-tuberculosis, with 1599 and 1445 as early lead candidates within this group. In order to evaluate and differentiate the pharmacological properties of these compounds and assist in candidate selection and design of optimal dosing regimens in animal models of Mtb infection, time kill curve assessments were performed in a previously established in vitro PK/PD model system. The performed studies and subsequent pharmacometric analysis indicate that the anti-mycobacterial activity of 1599 exhibits concentration-dependent killing whereas 1445 shows time-dependent killing. These findings are supported by the fact that the PKPD index that best describes bacterial killing is T > MIC for 1445, but fCmax/AUC for 1599. The differential killing behavior among the lead candidates can be rationalized by the differences in post-antibiotic effect: 15.7 h for 1445 compared the 133 h for 1599. Overall, the PK/PD based analysis of the in vitro pharmacologic killing profile of spectinamides 1599 and 1445 on mycobacteria provided valuable insights that contributed to lead candidate selection and preclinical development of these compounds.

High levels of susceptibility to new and older antibiotics in Neisseria gonorrhoeae isolates from Saskatchewan (2003-15): time to consider point-of-care or molecular testing for precision treatment?

OBJECTIVES: The antimicrobial susceptibility of Neisseria gonorrhoeae isolates from Saskatchewan was determined retrospectively (2003-15) to ascertain temporal trends to both current and older antimicrobials used for treatment. METHOD: The agar dilution method was used to test the antimicrobial susceptibilities of 685 isolates to seven antibiotics. RESULTS: Over the period, only three (0.4%) gonococcal isolates had reduced susceptibility to cefixime and/or ceftriaxone. All isolates were susceptible to spectinomycin. Over 95% of the isolates tested were susceptible to azithromycin except in 2010 and 2013 (27.6% and 7.2% resistant, respectively). One isolate was resistant to both azithromycin and cefixime. Ciprofloxacin resistance was seen in < 5% of isolates prior to 2010, but in > 5% thereafter. From 2006 to 2012, and in 2015, penicillin resistance was detected in < 5% (0%-4.0%) of isolates, but in > 5% for the rest of the study period. Tetracycline resistance remained >5% (11.8%-89.1%) throughout the study. Plasmid-mediated resistance to tetracycline fluctuated between 0% and 17.5% of isolates tested. Four isolates were MDR and two isolates were XDR. CONCLUSIONS: N. gonorrhoeae isolates were largely susceptible (∼85%) to antibiotics no longer recommended for treatment, such as penicillin and ciprofloxacin. Gonorrhoea in Saskatchewan is primarily (>95%) diagnosed by nucleic acid amplification testing, which does not permit antimicrobial susceptibility testing. The development of molecular testing, or point-of-care tests, to evaluate antimicrobial susceptibility, would enhance knowledge of true levels of resistance and allow discretion as to whether older but still effective antibiotics could be used in individual patient care.

Aminomethyl spectinomycins as therapeutics for drug-resistant respiratory tract and sexually transmitted bacterial infections.

The antibiotic spectinomycin is a potent inhibitor of bacterial protein synthesis with a unique mechanism of action and an excellent safety index, but it lacks antibacterial activity against most clinically important pathogens. A series of N-benzyl-substituted 3'-(R)-3'-aminomethyl-3'-hydroxy spectinomycins was developed on the basis of a computational analysis of the aminomethyl spectinomycin binding site and structure-guided synthesis. These compounds had ribosomal inhibition values comparable to spectinomycin but showed increased potency against the common respiratory tract pathogens Streptococcus pneumoniae, Haemophilus influenzae, Legionella pneumophila, and Moraxella catarrhalis, as well as the sexually transmitted bacteria Neisseria gonorrhoeae and Chlamydia trachomatis. Non-ribosome-binding 3'-(S) isomers of the lead compounds demonstrated weak inhibitory activity in in vitro protein translation assays and poor antibacterial activity, indicating that the antibacterial activity of the series remains on target against the ribosome. Compounds also demonstrated no mammalian cytotoxicity, improved microsomal stability, and favorable pharmacokinetic properties in rats. The lead compound from the series exhibited excellent chemical stability superior to spectinomycin; no interaction with a panel of human receptors and drug metabolism enzymes, suggesting low potential for adverse reactions or drug-drug interactions in vivo; activity in vitro against a panel of penicillin-, macrolide-, and cephalosporin-resistant S. pneumoniae clinical isolates; and the ability to cure mice of fatal pneumococcal pneumonia and sepsis at a dose of 5 mg/kg. Together, these studies indicate that N-benzyl aminomethyl spectinomycins are suitable for further development to treat drug-resistant respiratory tract and sexually transmitted bacterial infections.

Twenty-five-year changing pattern of gonococcal antimicrobial susceptibility in Shanghai: surveillance and its impact on treatment guidelines.

BACKGROUND: Antimicrobial resistance of Neisseria gonorrhoeae is a serious health problem in China. Gonococcal antimicrobial susceptibility has been monitored in Shanghai since 1988. In this study, we examined the changing pattern of gonococcal antimicrobial susceptibility based on data from N. gonorrhoeae isolates collected over the past 25 years. METHODS: Approximately 100-200 isolates each year (1988-2013) were tested for their susceptibility to penicillin (PEN), tetracycline (TET), ciprofloxacin (CIP), ceftriaxone (CRO) and spectinomycin (SPT), using the agar dilution method. Plasmid-mediated N. gonorrhoeae antimicrobial resistance, comprising penicillinase-producing N. gonorrhoeae (presumed PPNG) and high-level tetracycline resistance N. gonorrhoeae (presumed TRNG), were also determined. Breakpoints for susceptibilities followed those described by the Clinical and Laboratory Standard Institute and the European Committee on Antimicrobial Susceptibility Testing. RESULTS: A high proportion of isolates were resistant to PEN, TET and CIP, ranging from less than 20% at the beginning of the survey, increasing in the late 1990s and reaching over 90% in recent years. The proportion of isolates exhibiting plasmid-mediated resistance exceeded 38% for presumed PPNG and 20% for presumed TRNG in recent years. The proportion of CRO nonsusceptible isolates (MIC ≥ 0.125 mg/L) ranged from 7% to 13% in most of the study years. Almost all isolates were susceptible to SPT. The SPT MIC90 was 16-32 mg/L for 2008-2013. The proportion of CRO nonsusceptible-associated multiple-drug-resistant (MDR) isolates was over 5% in most of the study years. CONCLUSIONS: N. gonorrhoeae isolates in Shanghai were resistant to PEN, TET and CIP. Furthermore, CRO nonsusceptible and MDR isolates were prevalent. N. gonorrhoeae isolates were also found to be susceptible to SPT. It is recommended that the CRO dose be increased from currently recommended 250 mg to 500 mg and that SPT be an alternative in treating urogenital gonorrhea. Our findings highlight the importance of both regional and national surveillance programs for the prompt modification of treatment guidelines, vital in responding to the changing pattern of gonococcal antimicrobial susceptibility.

Treatment failure with 2 g of azithromycin (extended-release formulation) in gonorrhoea in Japan caused by the international multidrug-resistant ST1407 strain of Neisseria gonorrhoeae.

OBJECTIVES: Antimicrobial resistance in Neisseria gonorrhoeae is a major public health concern globally. We report the first verified treatment failure of gonorrhoea with 2 g of azithromycin (extended-release formulation) in Japan and characteristics of the corresponding N. gonorrhoeae isolates. METHODS: Pre- and post-treatment isolates (n = 4) were investigated by Etest for antimicrobial susceptibility. The isolates were examined for molecular epidemiology by multilocus sequence typing (MLST), N. gonorrhoeae multi-antigen sequence typing (NG-MAST) and multiple-locus variable-number tandem repeat analysis (MLVA), and for the presence of azithromycin resistance determinants (23S rRNA gene mutations, erm genes and mtrR mutations). RESULTS: All isolates were resistant to azithromycin (MIC 4 mg/L) and ciprofloxacin, but remained susceptible to cefixime, ceftriaxone and spectinomycin. All isolates were assigned to MLST ST1901 and NG-MAST ST1407 and three of four isolates possessed MLVA profile 8-3-21-16-1. All isolates contained the previously described C2599T mutation (N. gonorrhoeae numbering) in all four 23S rRNA alleles and the previously described single-nucleotide (A) deletion in the mtrR promoter region. CONCLUSIONS: This verified treatment failure occurred in a patient infected with an MLST ST1901/NG-MAST ST1407 strain of N. gonorrhoeae. While this international strain commonly shows resistance or decreased susceptibility to multiple antimicrobials, including extended-spectrum cephalosporins, the strain reported here remained fully susceptible to the latter antimicrobials. Hence, two subtypes of azithromycin-resistant gonococcal MLST ST1901/NG-MAST ST1407 appear to have evolved and to be circulating in Japan. Azithromycin should not be recommended as a single antimicrobial for first-line empirical treatment of gonorrhoea.

Plastid transformation in potato: Solanum tuberosum.

Although plastid transformation has attractive advantages and potential applications in plant biotechnology, for long time it has been highly efficient only in tobacco. The lack of efficient selection and regeneration protocols and, for some species, the inefficient recombination using heterologous flanking regions in transformation vectors prevented the extension of the technology to major crops. However, the availability of this technology for species other than tobacco could offer new possibilities in plant breeding, such as resistance management or improvement of nutritional value, with no or limited environmental concerns. Herein we describe an efficient plastid transformation protocol for potato (Solanum tuberosum subsp. tuberosum). By optimizing the tissue culture system and using transformation vectors carrying homologous potato flanking sequences, we obtained up to one transplastomic shoot per bombardment. Such efficiency is comparable to that usually achieved in tobacco. The method described in this chapter can be used to regenerate potato transplastomic plants expressing recombinant proteins in chloroplasts as well as in amyloplasts.

Plastid transformation in sugar beet: Beta vulgaris.

Chloroplast biotechnology has assumed great importance in the past 20 years and, thanks to the numerous advantages as compared to conventional transgenic technologies, has been applied in an increasing number of plant species but still very much limited. Hence, it is of utmost importance to extend the range of species in which plastid transformation can be applied. Sugar beet (Beta vulgaris L.) is an important industrial crop of the temperate zone in which chloroplast DNA is not transmitted trough pollen. Transformation of the sugar beet genome is performed in several research laboratories; conversely sugar beet plastome genetic transformation is far away from being considered a routine technique. We describe here a method to obtain transplastomic sugar beet plants trough biolistic transformation. The availability of sugar beet transplastomic plants should avoid the risk of gene flow between these cultivated genetic modified sugar beet plants and the wild-type plants or relative wild species.

Gonococcal resistance: evolving from penicillin, tetracycline to the quinolones in South Africa -- implications for treatment guidelines.

Resistant Neisseria gonorrhoeae has been evolving. This study assessed the antimicrobial susceptibility profile of isolates in the Pretoria region, South Africa. Isolates of N. gonorrhoeae from men with urethritis were tested for susceptibility to eight antimicrobial agents by disc diffusion, Etest and agar dilution methods. Chromosomal resistance to penicillin was found in 16% of isolates, 16% showed plasmid-mediated resistance and decreased susceptibility was seen in 73% of isolates. For the first time, there is evidence of high-level tetracycline resistance (36%). Ciprofloxacin resistance emerged at 7%. All isolates remained susceptible to ceftriaxone. In view of these findings of the emergence of quinolone-resistant N. gonorrhoeae, national treatment guidelines for syndromic management of sexually transmitted infections need to be urgently reviewed. The injectable preparation, ceftriaxone has to be considered as a first-line agent for the management of gonococcal infections. Overall, the gonococcal isolates in the Pretoria region remain susceptible to ceftriaxone, cefoxitin, cefpodoxime and spectinomycin.

Antimicrobial susceptibility among Neisseria gonorrhoeae in New Zealand in 2002.

AIM: To estimate the prevalence of antimicrobial resistance among Neisseria gonorrhoeae, and to determine whether the increase in ciprofloxacin resistance observed in Auckland in 2001 had occurred in other parts of the country. METHODS: The antimicrobial susceptibility of N. gonorrhoeae (isolated in New Zealand over a 4-month period between April and August 2002) was tested at either LabPlus, Auckland District Health Board, or at ESR, using the same agar dilution method. RESULTS: The prevalence of resistance to the antimicrobials tested was: ceftriaxone, 0%; ciprofloxacin, 6.8%; penicillin, 9.0%; spectinomycin, 0%; and tetracycline, 27.8%. There were few statistically significant geographical differences in resistance within New Zealand. Gonococcal infections acquired in Asia were more likely to be ciprofloxacin and penicillin resistant than infections acquired in New Zealand. CONCLUSIONS: Ciprofloxacin resistance among N. gonorrhoeae in New Zealand has reached a level where this antibiotic is no longer the most appropriate first-line treatment. In fact, ceftriaxone should now be considered the most reliable option for the treatment and control of gonorrhoea in New Zealand, particularly in the Northland/Auckland region.

Susceptibility testing of Actinobacillus pleuropneumoniae in Denmark. Evaluation of three different media of MIC-determinations and tablet diffusion tests.

This study was conducted to compare the applicability of three different media in sensitivity testing of Actinobacillus pleuropneumoniae by means of MIC and tablet diffusion tests. The media used were: modified PPLO agar, chocolatized Mueller-Hinton-II and Columbia agar supplemented with NAD. Seven antimicrobial agents were tested: ceftiofur, enrofloxacin, penicillin, spectinomycin, tiamulin, trimethoprim + sulfadiazine and tylosin, against 40 randomly selected A. pleuropneumoniae isolates. In general, good agreement was found between results obtained with all combinations of media, most antimicrobials tested and the two-test systems. Some variations between media were observed for spectinomycin, tiamulin and tylosin. For ceftiofur and trimethoprim + sulfadiazine some isolates with low MIC-values were classified as resistant using tablet diffusion, indicating that the break points of resistance for these antimicrobials using the tablet diffusion tests need adjustment. Using current break points for resistance with MIC-determinations, all isolates tested susceptible to ceftiofur, enrofloxacin, penicillin, tiamulin and trimethoprim + sulfadiazine. A larger number of isolates tested resistant to spectinomycin and tylosin on all three media using both MIC determinations and tablet diffusion.

Resistance in gonococci isolated in the WHO Western Pacific Region to various antimicrobials used in the treatment of gonorrhoea, 1997. WHO Western Pacific Gonococcal Antimicrobial Surveillance Programme-WHO WPR GASP.

The World Health Organization Western Pacific Region Gonococcal Antimicrobial Surveillance Programme (WHO WPR GASP) is a multicentric long term programme of continuous surveillance of the antibiotic susceptibility of Neisseria gonorrhoeae. In 1997 the programme examined the susceptibility of 8,594 isolates of gonococci to various antimicrobials in 15 focal points. The trend toward increased antimicrobial resistance noted in earlier years continued. The proportion of quinolone resistant gonococci reported from most centres was either maintained or else increased. More than half of the isolates tested in China-Hong Kong, China, Japan, Korea, and the Philippines had altered quinolone susceptibility and increases in the number and percentage of quinolone resistant strains were noted in most, but not all, of the other centres. Resistance to the penicillins was again widespread, and chromosomally mediated resistance was a significant factor. Penicillinase-producing Niesseria gonorrhoeae (PPNG) were present in all centres. All isolates were sensitive to the third generation cephalosporins and only a very few isolates in China were spectinomycin resistant. High level tetracycline resistance was concentrated in a number of centres including Singapore, Malaysia, the Philippines and Vietnam. The proportion of tetracycline resistant Neiserria gonorrhoeae (TRNG) in most of the remaining centres was less than 10 per cent.

Mutations at positions 13 and/or 914 in Escherichia coli 16S ribosomal RNA interfere with the initiation of protein synthesis.

Mutations at positions 13 (U-->A) and/or 914 (A-->U) of Escherichia coli 16S rRNA severely affect cell growth and protein synthesis, when expressed in vivo in a vector encoding an rrn operon under control of an inducible promoter. In vitro assays using extension inhibition indicate that the mutations interfere with the formation of the 30S translational initiation complex, which can account for their effect on cell growth. The two mutations destabilize an adjacent pseudoknot helix in which bases 17-19 pair to bases 916-918. This was shown by the increased binding of an oligodeoxyribonucleotide probe complementary to one strand of the pseudoknot helix, and by the increased reactivity to kethoxal of base G917 within this helix. These observations suggest that this pseudoknot helix participates in the formation of the 30S translational initiation complex.

Treatment of chancroid with a single dose of spectinomycin.

Fifty patients with lesions characteristic of chancroid were enrolled in an open-label prospective study to examine the efficacy of a single 2-gm dose of spectinomycin for treatment of chancroid. Only those patients (41 men; aged 18 to 49 years) with positive culture results for Haemophilus ducreyi were included in the analysis. Patients each received a single 2-gm dose of spectinomycin intramuscularly. The recovery process began on the third day of follow-up, as evidenced by the occurrence of epithelialization and a decrease in inflammation. By the seventh day after treatment, only one patient had ulcers; 40 patients experienced eradication of all ulcers (P less than 0.0001). The condition of nodes affected by infection also indicated efficacy of treatment (P less than 0.01); only one patient still had a swollen node by the fourteenth day after treatment. Of the 41 patients, 37 (90%) had negative culture results for H. ducreyi on the third day after treatment. Only 4 patients (10%) required a second dose of spectinomycin on the seventh day to affect a cure. Treatment with spectinomycin resulted in a 98% cure rate 14 days after treatment. The minimum inhibitory concentration (MIC) of spectinomycin was 1 microgram/mL to 3 micrograms/mL in the 15 strains studied. The drug was well tolerated and no adverse reactions were reported. It is concluded that a single 2-gm dose of spectinomycin is a safe and effective alternative drug for treatment of chancroid.

In vitro assessment of the efficacy of erythromycin in combination with oxytetracycline or spectinomycin against Pasteurella haemolytica.

The effects of combining erythromycin (Ery) with oxytetracycline (Oxy) or spectinomycin (Sp) on Pasteurella haemolytica were evaluated in vitro using the chessboard (checkerboard) technique. These combinations were selected because all are drugs widely used in bovine respiratory disease treatment, and they represent possible sequential or complementary mechanisms of action. Using the recommended breakpoints of greater than 4 micrograms/ml for Ery, 16 micrograms/ml for Oxy, and 32 micrograms/ml for Sp, of the 33 P. haemolytica isolates, 32 were resistant to Oxy, 27 to Sp, and 14 to Ery. Based on the fractional inhibitory concentration index, Ery and Oxy in combination were synergistic or additive against 32 of 33 isolates. The combination of Ery and Sp was synergistic or additive against 27 of 33 isolates. No instances of antagonism were seen. When the effects were considered within the context of therapeutically achievable serum/tissue concentrations, the effects of Ery and Oxy in combination were only marginal. Thus, against P. haemolytica isolates, Ery and Sp appeared to represent an effective antimicrobial combination, whereas Ery and Oxy were only of marginal efficacy as a combination.

Spectinomycin disk zone diameter as a predictor of outcome in clinical treatment of gonorrhea.

The MICs for 41 Neisseria gonorrhoeae strains from patients receiving spectinomycin treatment were determined by the agar dilution method and compared with the zones of inhibition produced by disks containing 100 micrograms of spectinomycin. Our data demonstrated a good correlation between the two methods. Moreover, a zone of inhibition of less than or equal to 15 mm was a good predictor of clinical treatment failures with spectinomycin.

[Epidemiological and therapeutic studies on gonococcal infections--one shot therapy by spectinomycin--[Sapporo Clinical Research Group for STD]].

From January through March of 1985, the Sapporo Clinical Research Group for STD treated 69 cases of gonococcal infections (61 cases of male gonococcal urethritis and 8 cases of female gonococcal cervicitis) at its facilities in Sapporo City. The therapeutic efficacy of one shot therapy of Spectinomycin (SPCM) was investigated, and an epidemiological study on the cases and bacteriological studies on the isolated strains of Neisseria gonorrhoeae were made. The male patients were between 19 and 55 years old, with a peak age distribution in the younger half of the twenties. The female patients were between 18 and 40 years old. The major source of infections was a so-called special massage parlor which accounted for 36.1% of male cases. The isolation rate of PPNG were 16.7% (11/66). The MIC (inoculum size; 10(6) CFU/ml) of SPCM ranged from 3.13 to 25 micrograms/ml regardless of beta-lactamase production. In male patients, the eradication rate (efficacy rate) of N. gonorrhoeae by SPCM was 94.7% on the first day, 93.6% on the third day and 100% on the seventh day after 2 g one shot therapy. In female patients, the rate was 100% on the third and seventh day after 2 g one shot therapy, and 75% on the first day, 66.7% on third day and 100% on seventh day after 4 g one shot therapy. We considered that one shot therapy of SPCM was effective for gonococcal infection also in the present time. Especially SPCM was effective for infections by PPNG, since it was not resolved by beta-lactamase of N. gonorrhoeae. Positive rate of Chlamydia trachomatis was 16.3% in male gonococcal urethritis, and the serous discharge tended to remain longer in the positive patients than in the negative patients. There was only one side effect (1.4%), therefore SPCM was recognized to be a safely administrated antimicrobial agent.

Randomised comparative study of ceftriaxone and spectinomycin in gonorrhoea.

From 26 April to 30 June 1983 a total of 200 men with uncomplicated gonococcal urethritis were randomly treated with either 2 g spectinomycin or 250 mg ceftriaxone, both administered intramuscularly. Of 197 isolates tested for the presence of the enzyme beta lactamase, 91 (46.2%) were positive (PPNG) and 106 (53.8%) were non-PPNG strains. All 93 patients treated with spectinomycin and followed up and 97 treated with ceftriaxone and followed up were cured. Ceftriaxone 250 mg administered by intramuscular injection is highly effective in treating gonococcal infections caused by both PPNG and non-PPNG strains and is an appropriate alternative to spectinomycin.