Increasingly limited options for the treatment of enteric fever in travellers returning to England, 2014-2019: a cross-sectional analytical study.

Introduction. Enteric fever (caused by Salmonella enterica serovars Typhi and Paratyphi) frequently presents as an acute, undifferentiated febrile illness in returning travellers, requiring timely empirical antibiotics.Gap Statement. Determining which empirical antibiotics to prescribe for enteric fever requires up-to-date knowledge of susceptibility patterns.Aim. By characterising factors associated with antimicrobial resistance in cases of S. Typhi and S. Paratyphi imported to England, we aim to guide effective empirical treatment.Methodology. All English isolates of S. Typhi and S. Paratyphi 2014-2019 underwent antimicrobial susceptibility testing; results were compared to a previous survey in London 2005-2012. Risk factors for antimicrobial resistance were analysed with logistic regression models to predict adjusted odds ratios (aOR) for resistance to individual antibiotics and multi-drug resistance.Results. We identified 1088 cases of S. Typhi, 729 S. Paratyphi A, 93 S. Paratyphi B, and one S. Paratyphi C. In total, 93 % were imported. Overall, 90 % of S. Typhi and 97 % of S. Paratyphi A isolates were resistant to ciprofloxacin; 26 % of S. Typhi were multidrug resistant to ciprofloxacin, amoxicillin, co-trimoxazole, and chloramphenicol (MDR+FQ). Of the isolates, 4 % of S. Typhi showed an extended drug resistance (XDR) phenotype of MDR+FQ plus resistance to third-generation cephalosporins, with cases of XDR rising sharply in recent years (none before 2017, one in 2017, six in 2018, 32 in 2019). For S. Typhi isolates, resistance to ciprofloxacin was associated with travel to Pakistan (aOR=32.0, 95 % CI: 15.4-66.4), India (aOR=21.8, 95 % CI: 11.6-41.2), and Bangladesh (aOR=6.2, 95 % CI: 2.8-13.6) compared to travel elsewhere, after adjusting for rising prevalence of resistance over time. MDR+FQ resistance in S. Typhi isolates was associated with travel to Pakistan (aOR=3.5, 95 % CI: 2.4-5.2) and less likely with travel to India (aOR=0.07, 95 % CI 0.04-0.15) compared to travel elsewhere. All XDR cases were imported from Pakistan. No isolate was resistant to azithromycin. Comparison with the 2005-2012 London survey indicates substantial increases in the prevalence of resistance of S. Typhi isolates to ciprofloxacin associated with travel to Pakistan (from 79-98 %) and Africa (from 12-60 %).Conclusion. Third-generation cephalosporins and azithromycin remain appropriate choices for empirical treatment of enteric fever in most returning travellers to the UK from endemic countries, except from Pakistan, where XDR represents a significant risk.

Ethnically diverse urban transmission networks of Neisseria gonorrhoeae without evidence of HIV serosorting.

OBJECTIVE: We aimed to characterise gonorrhoea transmission patterns in a diverse urban population by linking genomic, epidemiological and antimicrobial susceptibility data. METHODS: Neisseria gonorrhoeae isolates from patients attending sexual health clinics at Barts Health NHS Trust, London, UK, during an 11-month period underwent whole-genome sequencing and antimicrobial susceptibility testing. We combined laboratory and patient data to investigate the transmission network structure. RESULTS: One hundred and fifty-eight isolates from 158 patients were available with associated descriptive data. One hundred and twenty-nine (82%) patients identified as male and 25 (16%) as female; four (3%) records lacked gender information. Self-described ethnicities were: 51 (32%) English/Welsh/Scottish; 33 (21%) white, other; 23 (15%) black British/black African/black, other; 12 (8%) Caribbean; 9 (6%) South Asian; 6 (4%) mixed ethnicity; and 10 (6%) other; data were missing for 14 (9%). Self-reported sexual orientations were 82 (52%) men who have sex with men (MSM); 49 (31%) heterosexual; 2 (1%) bisexual; data were missing for 25 individuals. Twenty-two (14%) patients were HIV positive. Whole-genome sequence data were generated for 151 isolates, which linked 75 (50%) patients to at least one other case. Using sequencing data, we found no evidence of transmission networks related to specific ethnic groups (p=0.64) or of HIV serosorting (p=0.35). Of 82 MSM/bisexual patients with sequencing data, 45 (55%) belonged to clusters of ≥2 cases, compared with 16/44 (36%) heterosexuals with sequencing data (p=0.06). CONCLUSION: We demonstrate links between 50% of patients in transmission networks using a relatively small sample in a large cosmopolitan city. We found no evidence of HIV serosorting. Our results do not support assortative selectivity as an explanation for differences in gonorrhoea incidence between ethnic groups.

The management of sexually transmitted infections: a scoping survey in primary care.

BACKGROUND: National guidelines for sexually transmitted infections (STIs) in primary care exists but their management is uncertain. AIM: To assess the management of STIs against national standards in primary care. DESIGN & SETTING: A questionnaire based study in London and Brighton. The survey was conducted in 2015 following reorganisation of sexual health services in England. METHOD: Questionnaires were sent to GPs in London and Brighton about testing for STIs, treatment for gonorrhoea, specialist advice, and referral services. RESULTS: Of 119 GPs who responded, most expressed confidence in treating chlamydia (n = 105/119, 88%), trichomonas (n = 81/119, 68%), and herpes (n = 82/119, 69%) but not gonorrhoea (n = 32/119, 27%). Most referred cases of syphilis (n = 92/119, 77%) and genital warts (83/119, 70%) to genito-urinary medicine (GUM) as per guidance. Most GPs tested for gonorrhoea on patient request (n = 95/119, 80%), in tandem with chlamydia screening (n = 89/119, 75%), because of high risk status (n = 85/119, 71%) and genital symptoms (n = 108/119, 91%). Some GPs (n = 22/119, 18%) sampled urine for culture, 53/119 (45%) provided high vaginal swabs (HVS), and 28/119 (24%) provided self-taken vulvovaginal swabs (STVVS) for culture. These samples are not appropriate for gonococcal culture and not processed in the laboratory. Urethral swabs for men and endocervical swabs (ECS) are recommended for gonococcus culture. Over half (n = 60/102, 59%) of GPs did not treat gonorrhoea but some prescribed cefixime, ciprofloxacin, or azithromycin. Eighty-seven per cent (n = 104/119) sought advice from GUM, and 83/103 (81%) referred gonorrhoea nucleic acid amplification test (NAAT)-positive patients. CONCLUSION: There is scope for improvement of STIs management in primary care to ensure that patients are optimally investigated, treated, and referred.

What were the risk factors and trends in antimicrobial resistance for enteric fever in London 2005-2012?

Purpose. A study was undertaken to determine the risk factors and trends in antimicrobial resistance for enteric fever.Methodology. Demographic, antimicrobial susceptibility, typing and epidemiological data were examined for 2005-2012 in patients with enteric fever in London. Single and multivariable logistic regression was used to determine the risk factors associated with antibiotic resistance.Results. 453 cases with Salmonella enterica subsp. enterica serovar Paratyphi A, 17 with S. Paratyphi B and 611 with S. enterica subsp. enterica serovar Typhi were examined. For travellers, 335 (88 %) of S. Paratyphi A isolates were resistant to ciprofloxacin, but resistance to other antimicrobials was low. Almost 80 % (395) of the S. Typhi isolates were resistant to ciprofloxacin, 131 (26 %) to ampicillin, 131 (27 %) to chloramphenicol, 137 (28 %) to trimethoprim and 171 (28 %) to sulphonamide. None of the isolates were resistant to cephalosporins.A trend analysis for S. Typhi isolates showed no significant change in resistance to ampicillin, chloramphenicol, sulphonamide and trimethoprim or for multidrug resistance (P=0.38). Overall resistance to ciprofloxacin increased for S. Paratyphi A (P=0.018) and for S. Typhi (P<0.001) but fell for S. Typhi in 2011-2012. Resistance profiles were reflected by specific phage types and countries visited by the travellers.Conclusions. The proportion of S. Typhi strains resistant to ampicillin, chloramphenicol and cotrimoxazole remained steady for the period 2005-2012. There was a significant increase in a trend for resistance to ciprofloxacin which increased until 2010, followed by a fall in 2011-2012. S. Paratyphi resistance to ciprofloxacin increased until 2012. Specific phage types were associated with resistance to specific antimicrobials and travel abroad.

An extended genotyping framework for Salmonella enterica serovar Typhi, the cause of human typhoid.

The population of Salmonella enterica serovar Typhi (S. Typhi), the causative agent of typhoid fever, exhibits limited DNA sequence variation, which complicates efforts to rationally discriminate individual isolates. Here we utilize data from whole-genome sequences (WGS) of nearly 2,000 isolates sourced from over 60 countries to generate a robust genotyping scheme that is phylogenetically informative and compatible with a range of assays. These data show that, with the exception of the rapidly disseminating H58 subclade (now designated genotype 4.3.1), the global S. Typhi population is highly structured and includes dozens of subclades that display geographical restriction. The genotyping approach presented here can be used to interrogate local S. Typhi populations and help identify recent introductions of S. Typhi into new or previously endemic locations, providing information on their likely geographical source. This approach can be used to classify clinical isolates and provides a universal framework for further experimental investigations.

ESBL-Producing and Macrolide-Resistant Shigella sonnei Infections among Men Who Have Sex with Men, England, 2015.

In England in 2015, Shigella sonnei isolates from men who have sex with men produced extended-spectrum ß-lactamases and exhibited macrolide resistance. Whole-genome sequencing showed a close relationship among the isolates, which harbored a plasmid that was previously identified in a shigellosis outbreak among this population but has acquired a mobile element.

Whole-genome sequencing to determine transmission of Neisseria gonorrhoeae: an observational study.

BACKGROUND: New approaches are urgently required to address increasing rates of gonorrhoea and the emergence and global spread of antibiotic-resistant Neisseria gonorrhoeae. We used whole-genome sequencing to study transmission and track resistance in N gonorrhoeae isolates. METHODS: We did whole-genome sequencing of isolates obtained from samples collected from patients attending sexual health services in Brighton, UK, between Jan 1, 2011, and March 9, 2015. We also included isolates from other UK locations, historical isolates from Brighton, and previous data from a US study. Samples from symptomatic patients and asymptomatic sexual health screening underwent nucleic acid amplification testing; positive samples and all samples from symptomatic patients were cultured for N gonorrhoeae, and resulting isolates were whole-genome sequenced. Cefixime susceptibility testing was done in selected isolates by agar incorporation, and we used sequence data to determine multi-antigen sequence types and penA genotypes. We derived a transmission nomogram to determine the plausibility of direct or indirect transmission between any two cases depending on the time between samples: estimated mutation rates, plus diversity noted within patients across anatomical sites and probable transmission pairs, were used to fit a coalescent model to determine the number of single nucleotide polymorphisms expected. FINDINGS: 1407 (98%) of 1437 Brighton isolates between Jan 1, 2011, and March 9, 2015 were successfully sequenced. We identified 1061 infections from 907 patients. 281 (26%) of these infections were indistinguishable (ie, differed by zero single nucleotide polymorphisms) from one or more previous cases, and 786 (74%) had evidence of a sampled direct or indirect Brighton source. We observed multiple related samples across geographical locations. Of 1273 infections in Brighton (including historical data), 225 (18%) were linked to another case elsewhere in the UK, and 115 (9%) to a case in the USA. Four lineages initially identified in Brighton could be linked to 70 USA sequences, including 61 from a lineage carrying the mosaic penA XXXIV allele, which is associated with reduced cefixime susceptibility. INTERPRETATION: We present a whole-genome-sequencing-based tool for genomic contact tracing of N gonorrhoeae and demonstrate local, national, and international transmission. Whole-genome sequencing can be applied across geographical boundaries to investigate gonorrhoea transmission and to track antimicrobial resistance. FUNDING: Oxford National Institute for Health Research Health Protection Research Unit and Biomedical Research Centre.

Trends in antibiotic susceptibility of enteric fever isolates in East London.

BACKGROUND: The study sought evidence for changes in the proportions of antibiotic resistant strains among isolates of Salmonella enterica serovar Typhi (S. typhi) and Salmonella enterica serovar Paratyphi (S. paratyphi) between 2005 and 2012. METHODS: Blood culture isolates of S. typhi and S. paratyphi from patients attending Newham and The Royal London Hospitals were included in the study. The organisms were cultured on selective media and identified by Maldi-ToF, API 20E and serology. Minimum inhibitory concentrations (MICs) of augmentin, chloramphenicol, co-trimoxazole, ceftriaxone, ciprofloxacin and azithromycin were determined by E tests for 194 isolates. RESULTS: Median MICs of ciprofloxacin and ceftriaxone were stable at 0.5 mg/L and 0.125 mg/L, respectively. Chloramphenicol, azithromycin, co-trimoxazole and augmentin median MICs were 4 mg/L, 8 mg/L, 0.064 mg/L and 0.5 mg/L, respectively. MIC90 values were lower than the resistant breakpoint for ceftriaxone, azithromycin and augmentin, but were >256 mg/L for chloramphenicol, 32 mg/L for co-trimoxazole and 1 mg/L for ciprofloxacin. CONCLUSIONS: Antibiotic resistance remained stable for enteric fever isolates between 2005 and 2012. The isolates remained susceptible to augmentin, ceftriaxone and azithromycin over this period, but the MIC90 was greater than the resistant breakpoint for chloramphenicol, cotrimoxazole and ciprofloxacin. The implications for clinical practice are that isolates of S. typhi and S. paratyphi from East London remain sensitive to ceftriaxone and azithromycin.

Enteric fever and its impact on returning travellers.

Enteric fever, a systemic illness, is caused by Salmonella enterica serovar Typhi or S. enterica serovar Paratyphi A, B or C. The organism is transmitted to humans by the faecal oral route and is endemic in countries with poor sanitation and lacking clean drinking water. There are around 27 million individuals infected with S. Typhi worldwide annually. Enteric fever is a particular problem in travellers to endemic areas, especially those visiting friends and relatives. Currently, the two main vaccines recommended for travellers are the Vi polysaccharide vaccine and the oral Ty21a vaccine. These internationally licensed vaccines are safe and effective against S. Typhi. However, there is currently no commercially available vaccine against S. Paratyphi, which is increasingly reported as a cause of enteric fever. Vaccine uptake and taking appropriate precautions are poor in travellers visiting friends and relatives abroad; this problem requires addressing. Ciprofloxacin is no longer recommended for empirical treatment of infection because of increasing reports of resistance, especially from South Asia. Ceftriaxone and azithromycin are currently the most commonly used antimicrobials for empirical treatment of enteric fever but resistance to both these agents is emerging.

East London experience with enteric fever 2007-2012.

PURPOSE: The clinical presentation and epidemiology for patients with enteric fever at two hospitals in East London during 2007-2012 is described with the aim to identify preventive opportunities and to reduce the cost of treatment. METHODS: A retrospective analysis of case notes from patients admitted with enteric fever during 2007 to 2012 with a microbiologically confirmed diagnosis was undertaken. Details on clinical presentation, travel history, demographic data, laboratory parameters, treatment, patient outcome and vaccination status were collected. RESULTS: Clinical case notes were available for 98/129 (76%) patients including 69 Salmonella enterica serovar Typhi (S. Typhi) and 29 Salmonella enterica serovar Paratyphi (S. Paratyphi). Thirty-four patients (35%) were discharged from emergency medicine without a diagnosis of enteric fever and then readmitted after positive blood cultures. Seventy-one of the 98 patients (72%) were UK residents who had travelled abroad, 23 (23%) were foreign visitors/new entrants to the UK and four (4%) had not travelled abroad. Enteric fever was not considered in the initial differential diagnosis for 48/98 (49%) cases. The median length of hospital stay was 7 days (range 0-57 days). The total cost of bed days for managing enteric fever was £454,000 in the two hospitals (mean £75,666/year). Median time to clinical resolution was five days (range 1-20). Seven of 98 (7%) patients were readmitted with relapsed or continued infection. Six of the 71 (8%) patients had received typhoid vaccination, 34 (48%) patients had not received vaccination, and for 31 cases (44%) vaccination status was unknown. CONCLUSIONS: Further interventions regarding education and vaccination of travellers and recognition of the condition by emergency medicine clinicians in travellers to South Asia is required.

Whole-genome enrichment and sequencing of Chlamydia trachomatis directly from clinical samples.

BACKGROUND: Chlamydia trachomatis is a pathogen of worldwide importance, causing more than 100 million cases of sexually transmitted infections annually. Whole-genome sequencing is a powerful high resolution tool that can be used to generate accurate data on bacterial population structure, phylogeography and mutations associated with antimicrobial resistance. The objective of this study was to perform whole-genome enrichment and sequencing of C. trachomatis directly from clinical samples. METHODS: C. trachomatis positive samples comprising seven vaginal swabs and three urine samples were sequenced without prior in vitro culture in addition to nine cultured C. trachomatis samples, representing different serovars. A custom capture RNA bait set, that captures all known diversity amongst C. trachomatis genomes, was used in a whole-genome enrichment step during library preparation to enrich for C. trachomatis DNA. All samples were sequenced on the MiSeq platform. RESULTS: Full length C. trachomatis genomes (>95-100% coverage of a reference genome) were successfully generated for eight of ten clinical samples and for all cultured samples. The proportion of reads mapping to C. trachomatis and the mean read depth across each genome were strongly linked to the number of bacterial copies within the original sample. Phylogenetic analysis confirmed the known population structure and the data showed potential for identification of minority variants and mutations associated with antimicrobial resistance. The sensitivity of the method was >10-fold higher than other reported methodologies. CONCLUSIONS: The combination of whole-genome enrichment and deep sequencing has proven to be a non-mutagenic approach, capturing all known variation found within C. trachomatis genomes. The method is a consistent and sensitive tool that enables rapid whole-genome sequencing of C. trachomatis directly from clinical samples and has the potential to be adapted to other pathogens with a similar clonal nature.

A selected screening programme was less effective in the detection of methicillin-resistant Staphylococcus aureus colonisation in an orthopaedic unit.

PURPOSE: Our unit has used a selective screening policy for methicillin-resistant Staphylococcus aureus (MRSA) colonisation using standard chromogenic growth media, based upon risk stratification. The aim of this study was to examine the effectiveness of this selective screening policy. METHODS: A cohort of 429 patients was assessed for their risk status for MRSA colonisation using both rapid polymerase chain reaction (PCR) swabs and traditional culture and sensitivity analysis. The sensitivity, specificity, positive predictive values and negative predictive values of the traditional selective approach were calculated compared to universal rapid screening. RESULTS: One hundred eighteen patients were considered high risk and would traditionally be further screened with standard culture of swabs. The prevalence of MRSA was 15/429 (3.5%). The sensitivity of selective screening was 53% identifying eight of 15 cases. The false-negative rate was therefore 47% and seven would have been missed. PCR results were available within four to six hours, whereas culture results were only available at 24 hours for the media showing no growth and not until 72 hours for positive MRSA cases. CONCLUSIONS: We now advocate universal screening prior to, or on admission, using this rapid PCR test, as we consider this identifies MRSA colonisation more effectively and facilitates "ring-fencing" of orthopaedic beds.

Be vigilant for secondary periprosthetic joint infection.

Periprosthetic joint infection (PJI) is caused by haematogenous spread from a distant primary infection in 70% of deep infections. It can potentially be avoided by prompt recognition and treatment of the primary infection focus in susceptible patients. Streptococci are commonly implicated in such secondary infections. Group A, B, C and G streptococci can cause invasive, potentially life-threatening infection. Risk factors include diabetes, immunodeficiency and venous insufficiency Any patient with a joint replacement should be counselled to seek early attention for any soft tissue or dental infection. A course of antibiotics should be considered in any wound in which there has been significant contamination. Patients at risk of infection through impaired physical defences such as chronic venous insufficiency should be treated appropriately and consideration should be given to prophylactic treatment of varicose veins if there are early signs of chronic venous insufficiency. Mild, uncomplicated cellulitis can be treated with oral antibiotics, simple penicillin agents such as amoxicillin or flucloxacillin should be administered. Patients should be referred to hospital for consideration of parenteral antibiotics if they are exhibiting signs of systemic sepsis such as tachycardia, pyrexia or hypotension. PJI should be suspected if a patient with a joint replacement develops pain in that joint after a soft tissue, respiratory tract or dental infection. In cases of suspected PJI prompt orthopaedic advice should be sought and antibiotics withheld.

Positive predictive value of the Becton Dickinson VIPER system and the ProbeTec GC Q x assay, in extracted mode, for detection of Neisseria gonorrhoeae.

OBJECTIVES: Performance of the new Becton Dickinson ProbeTec GC Q(x) assay on the BD VIPER platform was evaluated to ascertain whether confirmatory testing is required in our clinical setting. METHODS: Positive predictive value (PPV) was determined by comparison with culture and a confirmatory nucleic acid amplification test (NAAT)-based Neisseria gonorrhoeae assay from genital and extragenital samples (rectal and pharyngeal) collected from a genitourinary medicine (GUM) clinic. RESULTS: Among 14,223 clinical genital samples, 149 (1.0%) specimens were positive using the ProbeTec GC Q(x) assay, automated on the VIPER platform; 141 of these were confirmed by either culture or a real-time PCR targeting two gonococcal-specific targets (PPV 94.6%; 95% CI 90% to 98%). Among 840 pharyngeal samples, 26 (3.1%) were positive by the ProbeTec GC Q(x) assay; 13 were confirmed (PPV 50%; 95% CI 30% to 70%). Among 593 rectal samples, 17 tested positive by the ProbeTec GC Q(x) assay; all were confirmed (PPV 100%; 95% CI 80% to 100%). CONCLUSIONS: The lower 95% CI of the PPV for the ProbeTec GC Q(x) assay for genital specimens was >90% in this GUM clinic population, and therefore confirmatory testing for genital specimens is not required. Confirmatory testing of pharyngeal and rectal samples should continue in line with national guidelines.

High-level azithromycin resistance occurs in Neisseria gonorrhoeae as a result of a single point mutation in the 23S rRNA genes.

High-level azithromycin resistance (AZM-HR), defined as a MIC of > or = 256 mg/liter, emerged in Neisseria gonorrhoeae in the United Kingdom in 2004. To determine the mechanism of this novel phenotype, isolates from the United Kingdom that were AZM-HR (n, 19), moderately AZM resistant (MICs, 2 to 8 mg/liter) (n, 26), or sensitive (MICs, 0.12 to 0.25 mg/liter) (n, 4) were screened for methylase (erm) genes and for mutations in the mtrR promoter region, associated with efflux pump upregulation. All AZM-resistant isolates and 12 sensitive isolates were screened for mutations in domain V of each 23S rRNA allele. All AZM-HR isolates contained the A2059G mutation (Escherichia coli numbering) in three (3 isolates) or four (16 isolates) 23S rRNA alleles. Most (22/26) moderately AZM resistant isolates contained the C2611T mutation in at least 3/4 alleles. The remainder contained four wild-type alleles, as did 8/12 sensitive isolates, while one allele was mutated in the remaining four sensitive isolates. Serial passage of AZM-sensitive colonies on an erythromycin-containing medium selected AZM-HR if the parent strain already contained mutation A2059G in one 23S rRNA allele. The resultant AZM-HR strains contained four mutated alleles. Eight isolates (five moderately AZM resistant and three AZM-HR) contained mutations in the mtrR promoter. No methylase genes were detected. This is the first evidence that AZM-HR in gonococci may result from a single point mutation (A2059G) in the peptidyltransferase loop in domain V of the 23S rRNA gene. Mutation of a single allele is insufficient to confer AZM-HR, but AZM-HR can develop under selection pressure. The description of a novel resistance mechanism will aid in screening for the AZM-HR phenotype.

Emergence and spread of azithromycin-resistant Neisseria gonorrhoeae in Scotland.

OBJECTIVES: The aim of this study was to analyse the trend in azithromycin susceptibility (AzDS) of Neisseria gonorrhoeae in Scotland between April 2004 and December 2007, and to characterize isolates exhibiting decreased AzDS or high-level azithromycin resistance (AzHLR). METHODS: Antibiotic susceptibility testing and N. gonorrhoeae multiantigen sequence typing (NG-MAST) were performed on all gonococcal isolates received by the Scottish Bacterial Sexually Transmitted Infections Reference Laboratory (SBSTIRL) during the study period. RESULTS: AzHLR isolates were observed for the first time in 2004 and increased from 0.3% to 3.9% in 2007. AzDS declined from 2.1% to 1.3% in the same period. Taken together, AzDS and AzHLR isolates accounted for 5.2% of the gonococcal infections in Scotland in 2007. NG-MAST revealed that only a small number of sequence types (STs) contained AzHLR and AzDS isolates; these STs also included azithromycin-susceptible isolates. Most STs containing AzHLR isolates were genetically related on the basis of their por and tbpB alleles; however, demographic data suggested that they formed discrete sexual networks. CONCLUSIONS: AzHLR strains of N. gonorrhoeae are increasing in Scotland. A 1 g dose of azithromycin should not be considered as an alternative antibiotic therapy for gonococcal infections. The use of azithromycin to treat chlamydia in patients co-infected with N. gonorrhoeae results in a level of azithromycin in vivo that is sublethal for N. gonorrhoeae, which may lead to resistance.

Frequency of biocide resistance genes, antibiotic resistance and the effect of chlorhexidine exposure on clinical methicillin-resistant Staphylococcus aureus isolates.

OBJECTIVES: To detect genes conferring resistance to biguanides, quaternary ammonium compounds, beta-lactams and fluoroquinolones in clinical methicillin-resistant Staphylococcus aureus (MRSA) and to demonstrate whether reduced susceptibility is spread clonally and if the presence of any of the detected genes links to a specific epidemic MRSA. Finally, to identify if exposure to chlorhexidine may cause reduced susceptibility to antibiotics and chlorhexidine. METHODS: In total, 120 clinical MRSA isolates were isolated. qacA/B, qacG, qacH, norA, smr and blaZ genes were amplified by PCR. MICs of eight antibiotics were determined and PFGE was used for typing. Surface disinfection and residue tests were performed for chlorhexidine and a selection of isolates. RESULTS: qacA/B (8.3%), qacH (3.3%), norA (36.7%), smr (44.2%) and blaZ (97.5%) were prevalent within the population but qacG was not detected. EMRSA-15 (19.2%), EMRSA-16 (15%), P3 (15%) and H (12.5%) were the most common PFGE types. Clinical isolates demonstrated various degrees of susceptibility to chlorhexidine in the surface disinfection [mean microbiocidal effect (ME) = 0-1.91] and biocide residue (mean ME = 0.29-3.74) tests. Increases in post-exposure MICs were observed in both EMRSA-16 and the susceptible S. aureus control. CONCLUSIONS: In our study, isolates resembling PFGE type EMRSA-16 harboured more biocide resistance genes than other types. The observed reduction in susceptibility of clinical isolates to chlorhexidine may mean that a selective pressure is being exerted by residues in the clinical environment, and highlights the importance of efficacy testing on clinical strains and good infection control practices. The development of reduced microbial susceptibility to biocides represents a serious cause for concern in the clinical environment.

Antibiotic resistance in general dental practice--a cause for concern?

This review examines the contribution dental prescribing makes to the selection of antibiotic resistance in bacteria of the oral flora. The antibiotics commonly used in dental prescribing in the UK are discussed, together with the problems of resistance in members of the oral flora. The antibiotic prescribing habits of general dental practitioners are then reviewed with respect to therapeutic prescriptions and those drugs that are prescribed prophylactically. Not all antibiotic prescriptions for dental problems are written by dentists; prescribing outside the dental profession is also considered. The review then considers the support available to dentists from clinical diagnostic microbiology laboratories. It concludes that better use of diagnostic services, surveillance and improvements in dental education are required now to lessen the impact of antibiotic resistance in the future.