Prevalence, drivers and surveillance of antibiotic resistance and antibiotic use in rural China: Interdisciplinary study.

This study aimed to characterise antibiotic prescribing and dispensing patterns in rural health facilities in China and determine the community prevalence of antibiotic resistance. We investigated patterns and drivers of antibiotic use for common respiratory and urinary tract infections (RTI/UTI) in community settings, examined relationships between presenting symptoms, clinical diagnosis and microbiological results in rural outpatient clinics, and assessed potential for using patient records to monitor antibiotic use. This interdisciplinary mixed methods study included: (i) Observations and exit interviews in eight village clinics and township health centres and 15 retail pharmacies; (ii) Urine, throat swab and sputum samples from patients to identify potential pathogens and test susceptibility; (iii) 103 semi-structured interviews with doctors, patients, pharmacy workers and antibiotic-purchasing customers; (iv) Assessment of completeness and accuracy of electronic patient records through comparison with observational data. 87.9% of 1123 recruited clinic patients were prescribed antibiotics (of which 35.5% contained antibiotic combinations and >40% were for intravenous administration), most of whom had RTIs. Antibiotic prescribing for RTIs was not associated with presence of bacterial pathogens but was correlated with longer duration of infection (OR = 3.33) and presence of sore throat (OR = 1.64). Fever strongly predicted prescription of intravenous antibiotics (OR = 2.87). Resistance rates in bacterial pathogens isolated were low compared with national data. 25.8% of patients reported antibiotics use prior to their clinic visit, but only 56.2% of clinic patients and 53% of pharmacy customers could confirm their prescription or purchase included antibiotics. Diagnostic uncertainty, financial incentives, understanding of antibiotics as anti-inflammatory and limited doctor-patient communication were identified as key drivers of antibiotic use. Completion and accuracy of electronic patient records were highly variable. Prevalence of antibiotic resistance in this rural population is relatively low despite high levels of antibiotic prescribing and self-medication. More systematic use of e-records and in-service training could improve antibiotic surveillance and stewardship in rural facilities. Combining qualitative and observational anthropological methods and concepts with microbiological and epidemiological investigation of antibiotic resistance at both research design and analytic synthesis stages substantially increases the validity of research findings and their utility in informing future intervention development.

The pharmacodynamics of minocycline alone and in combination with rifampicin against Staphylococcus aureus studied in an in vitro pharmacokinetic model of infection.

BACKGROUND: Tetracyclines are widely used as oral therapy of MRSA infection, however, the pharmacodynamic underpinning is absent. OBJECTIVES: We employed an in vitro pharmacokinetic model to study the pharmacodynamics of minocycline alone and in combination with rifampicin. METHODS: An exposure-ranging design was used to establish fAUC/MIC targets for static, -1 log drop and -2 log drop effects against Staphylococcus aureus for minocycline and in combination with rifampicin. We then simulated 7-10 day human dosing of minocycline and the combination. RESULTS: The minocycline fAUC/MIC for 24 h static effect and -1 log drop in bacterial load were 12.5 ±â€Š7.1 and 23.3 ±â€Š12.4. fAUC/MIC targets for static and -1 log drop were greater at 48 and 72 h. The addition of simulated free rifampicin associated with dosing 300 mg q12h reduced the 24 h minocycline fAUC/MICs. Simulations performed over 7-10 days exposure indicated that for minocycline standard human doses there was a 1-3 log reduction in viable count and no changes in population profiles. Addition of rifampicin resulted in larger reductions in staphylococcal load but emergence of resistance to rifampicin. There was no resistance to minocycline. CONCLUSIONS: An fAUC/MIC minocycline target of 12-36 is appropriate for S. aureus. Addition of rifampicin decreases bacterial load but results in emergence of resistance to rifampicin. Unusually, there was no emergence of resistance to minocycline.

In vitro pharmacodynamics of omadacycline against Escherichia coli and Acinetobacter baumannii.

BACKGROUND: The pharmacodynamics of omadacycline have been extensively studied against Gram-positive pathogens but less information is available for Gram-negative pathogens. We describe the pre-clinical pharmacodynamics of omadacycline against Escherichia coli and Acinetobacter baumannii. METHODS: An in vitro dilutional pharmacokinetic model was used. Exposure experiments with fAUC/MIC ratios ranging from 0 to 1200 were performed using five strains of E. coli and five strains of A. baumannii. Reduction in bacterial load and changes in population profiles were measured. RESULTS: The fAUC/MIC targets against E. coli for 24 h static and -1 log reduction in load were 25.3 ±â€Š17.2 and 42.7 ±â€Š32.5, respectively. For A. baumannii the fAUC/MIC for 24 h static effect was 108.1 ±â€Š38.6. Changes in population profiles were observed for E. coli at fAUC/MIC ratios of ≤200 and for A. baumannii up to 1200. MICs were increased 2-32 fold. CONCLUSIONS: fAUC/MIC targets for A. baumannii are greater than for E.coli and changes in population profiles more likely. E. coli fAUC/MIC targets align with in vivo data and will be useful in determining omadacycline dosing for this pathogen.

Pregnant women's use of e-cigarettes in the UK: a cross-sectional survey.

OBJECTIVE: To estimate prevalence of vaping in pregnancy. Compare characteristics and attitudes between exclusive smokers and vapers, and between exclusive vapers and dual users (smoke and vape). DESIGN: Cross-sectional survey. SETTING: Hospitals across England and Scotland. POPULATION: Pregnant women attending antenatal clinics in 2017. METHODS: Women at 8-24 weeks' gestation completed screening questions about their smoking and vaping. Current or recent ex-smokers and/or vapers completed a full detailed survey about vaping and smoking. MAIN OUTCOME MEASURES: The prevalence of vaping, characteristics and attitudes of women who vape and/or smoke. RESULTS: Of 3360 pregnant women who completed screening questions, 515 (15.3%, 95% CI 14.1-16.6) were exclusive smokers, 44 (1.3%, 95% CI 1.0-1.8) exclusive vapers and 118 (3.5%, 95% CI 2.9-4.2) dual users. In total, 867 (25.8%) women completed the full survey; compared with smokers (n = 434), vapers (n = 140) were more likely to hold higher educational qualifications (odds ratio [OR) 1.51, 95% CI 1.01-2.25). Compared with exclusive vapers (n = 33), dual users (n = 107) were younger (OR 0.91 95% CI 0.85-0.98) and less likely to hold high qualifications (OR 0.43, 95% CI 0.20-0.96). Compared with smokers, dual users were more likely to be planning to quit smoking (OR 2.27, 95% CI 1.24-4.18). Compared with smokers, vapers were more likely to think vaping was safer than smoking (78.6% versus 36.4%). CONCLUSIONS: One in 20 pregnant women report vaping, and most also smoke. Dual users are more motivated towards stopping smoking than smokers. Where women have tried but cannot stop smoking, clinicians could encourage them to consider vaping for smoking cessation. TWEETABLE EXTRACT: One in 20 women report vaping during pregnancy but of those that do vape, most also smoke, despite having intentions to quit.

An in vitro biofilm model of Staphylococcus aureus infection of bone.

Chronic osteomyelitis is difficult to treat, with biofilm growth and the diffusion barrier to antibiotics presented by bone contributory factors. The aim of this study was to develop and evaluate an in vitro model of osteomyelitis. A bioluminescent strain of Staphylococcus aureus was grown in bone blocks made from bovine femur. Light output was insufficient for detection of bacterial cells within bone by 24 h and viable counting of crushed bone blocks was used to determine bacterial survival. Challenge of 72 h biofilms with gentamicin and daptomycin for 24 h demonstrated that only concentrations of 10 times the clinical peak serum target levels (100 mg l-1 gentamicin and 1000 mg l-1 daptomycin) resulted in significant reductions in cell viability compared to controls. Once daily dosing over 7 days resulted in ≥3 log reductions in cell numbers by 48 h. Thereafter no significant reduction was achieved, although emergence of resistance was suppressed. Determination of antibiotic concentration in bone blocks over 7 days indicated that neither agent was able to consistently reach levels in bone of >10% of the original dose. The model was, therefore, able to demonstrate the challenges posed by biofilm growth on and within bone. SIGNIFICANCE AND IMPACT OF THE STUDY: The majority of studies of antibiotic efficacy in the treatment of chronic osteomyelitis are carried out in animals. We developed an in vitro model of Staphylococcus aureus infection of bone to evaluate the ability of antibiotics to eradicate mature biofilms on surfaces analogous to necrotic bone. The results demonstrated the difficulties which occur in osteomyelitis treatment, with only very high concentrations of antibiotic able to penetrate the bone sufficiently to reduce bacterial survival whilst still failing to eradicate biofilms. This model could be of use in initial screening of novel compounds intended for use in the treatment of osteomyelitis.

Comparative antibacterial effects of moxifloxacin and levofloxacin on Streptococcus pneumoniae strains with defined mechanisms of resistance: impact of bacterial inoculum.

OBJECTIVES: We aim to further define the impact of the mechanism of fluoroquinolone resistance and inoculum load on the pharmacodynamic effects of levofloxacin and moxifloxacin on Streptococcus pneumoniae. METHODS: The antibacterial effects of and emergence of resistance (EoR) to moxifloxacin (400 mg once daily) or levofloxacin (750 mg once daily or 500 mg twice daily) were compared using five S. pneumoniae strains containing no known resistance mechanisms, efflux resistance mechanisms, a parC mutation or parC and gyrA mutations, at high (10(8) cfu/mL) and low (10(6) cfu/mL) inocula. An in vitro pharmacokinetic model was used and simulations were performed over 96 h. After drug exposure, isolates were tested for the presence of efflux pumps and mutations in the quinolone resistance-determining regions. RESULTS: A high inoculum diminished the antibacterial effect of moxifloxacin and levofloxacin. Levofloxacin at both dosages produced EoR with all strains. Levofloxacin regimens with AUC/MIC ratios <100 produced EoR. Moxifloxacin produced EoR with the parC strain only. CONCLUSIONS: Levofloxacin dosing regimens with low AUC/MIC ratios select for efflux pump overexpression, leading to fluoroquinolone resistance. Levofloxacin dosing may select for gyrA mutations, inducing moxifloxacin resistance. These data confirm that a fluoroquinolone AUC/MIC ratio of >100 is required for prevention of EoR.

Factors influencing the clinical outcome of methicillin-resistant Staphylococcus aureus bacteraemia.

Methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia is associated with high mortality due to a combination of host, pathogen and therapy related factors. This was a retrospective exploratory study to evaluate host, pathogen and therapy related factors influencing the clinical outcome of MRSA bacteraemia in a UK teaching hospital setting. Of the 38 consecutive episodes of MRSA bacteraemia over a 1-year period, 16 of 38 (40%) patients died at 1 month and 21/38 (55%) died at 6 months. Univariate analysis revealed age (p < 0.006), mean serum vancomycin level (p < 0.035), agr group I (p < 0.036) and set4-var2_11 gene (p < 0.036) at 1 month; and age (p < 0.004) and set4-var2_11 gene (p < 0.002) at 6 months as significant factors. However, there was no association between first trough vancomycin concentration and outcome at 1 month. Multivariate survival analysis from time of admission showed, for each one year increase in age, a patient is 1.121 (95% CI 1.006-1.250, p < 0.007) times more likely to die at any particular point in time, and patients with a mean serum vancomycin level of <10 mg/L, the odds ratio of adverse outcome is 16.129 (95% CI 2.398-111.111) compared to patients with a mean serum level >10 mg/L. A variety of host, pathogen, and therapy related factors influence the clinical outcome of MRSA bacteraemia.

Topical ethyl chloride fine spray. Does it have any antimicrobial activity?

AIM: The aim of this study was to assess whether ethyl chloride fine spray (Cryogesic) has antimicrobial activity. MATERIAL AND METHODS: Blood agar plates supplemented with 5% horse blood were inoculated with five different organisms, coagulase-negative staphylococci (CNS), methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA), Streptococcus pyogenes and Enterococcus faecalis. The plates were assessed for growth inhibition at 24 and 48 h by the microbiologist and compared with the non-sprayed control plates. RESULTS: The model showed a highly significant (p<0.0001) reduction in bacterial count for the plates treated with fine ethyl chloride spray. The estimate of the percentage of bacteria remaining after spraying with ethyl chloride was 42.7%, with a 95% confidence interval of 35.9-50.9%. There was no evidence that the effect of ethyl chloride fine spray was different for the different organisms (p=0.49). CONCLUSION: The use of ethyl chloride shows bacterial count reduction but the clinical implication of this needs to be determined. The authors postulate that any statistically significant reduction can only be helpful in reducing the infection rates. This coupled with the already proven local anaesthetic effects of ethyl chloride will make it an important tool for procedures like arthrocentesis and venepunctures.

Should finger rings be removed prior to scrubbing for theatre?

Finger rings increase surface bacterial counts. Although scrubbing reduces these (P=0.05), there are more bacteria under rings than on adjacent skin or the opposite hand. If rings are removed before scrubbing, bacterial counts are reduced but remain higher than on adjacent skin or the opposite hand. Ideally, finger rings should not be worn by theatre staff. However, if they are, they should be removed prior to scrubbing for surgical operations.

Topical fusidic acid/betamethasone-containing gel compared to systemic therapy in the treatment of canine acute moist dermatitis.

The efficacy of a topical preparation containing 0.5% fusidic acid and 0.1% betamethasone-17-valerate was compared to a systemic therapy (comprising a combination of parenteral dexamethasone and oral clavulanate-potentiated amoxycillin) in the treatment of 104 dogs with acute moist dermatitis. Significant improvement was evident after seven days in both treatment groups in all clinical parameters assessed and there was no significant difference in the overall response between the two treatment groups. Staphylococcus intermedius was the most frequently isolated organism from swabs at the first visit (Day 0). No resistance to fusidic acid or clavulanate-potentiated amoxycillin was encountered. The study demonstrates no difference in the clinical improvement achieved in canine acute moist dermatitis following topical or systemic therapy and that both treatment regimes represent effective treatment options for the condition.

In vitro studies on the impact of human serum on the antibacterial effect of faropenem.

The interaction between faropenem and serum in determining antibacterial effect was studied using three target pathogens and two different in vitro methodologies. Strains of Staphylococcus aureus, Streptococcus pneumoniae, capsulate and non capsulate Haemophilus influenzae, all faropenem MIC 0.12 mg/L, were tested in a range of pharmacologically realistic faropenem concentrations with various proportions of serum up to 75%. Using simulated serum bactericidal titres the presence of human serum reduced the activity of faropenem against S. pneumoniae as did heat-treated serum for non-capsulate H. influenzae. Serum on its own was bactericidal against H. influenzae probably due to the presence of complement. The antibacterial effects of combinations of faropenem and serum was assessed in time-kill curves by calculation of the area-under-the bacterial-kill-curve (AUBKC). This was then related to faropenem concentration and the proportion of serum using three-dimensional plots. Serum on its own was mildly inhibitory of the growth of S. aureus, supported improved growth of S. pneumoniae at some proportions and was rapidly bactericidal to H. influenzae, especially the non-capsulate strains. Faropenem had a marked antibacterial effect against all three species in the range 0-2.5 mg/L. Increasing the faropenem concentration from 2.5-10 mg/L produced little or no additional effect. The combination of serum and faropenem had little impact on the antibacterial effect against S. pneumoniae and S. aureus but free drug concentrations were likely to be greater than the MIC in all the combinations used. Against capsulate H. influenzae the effect of serum and faropenem was broadly equivalent while against non-capsulate strains the activity of serum was so great it is difficult to assess the impact of faropenem alone. The interaction between serum and antibiotic in determining antibacterial effect is complex and critically dependent on the proportions of serum and drug concentrations chosen. Three-dimensional plots offer a tool to visualise these complex relationships which may be species specific.

In vitro activities of nine peptide deformylase inhibitors and five comparator agents against respiratory and skin pathogens.

The activity of nine peptide deformylase (PDF) inhibitors undergoing clinical evaluation were compared with co-amoxiclav, levofloxacin, moxifloxacin, erythromycin and telithromycin against a range of respiratory and skin pathogens (n=166). The PDF inhibitor showed good activity against Streptococcus pneumoniae, Moxarella catarrhalis, Group A streptococci and Staphylococcus aureus irrespective of beta-lactam or fluoroquinolone susceptibility. Against Haemophilus influenzae, MIC(90) values were generally higher. BB-88488 was the most active compound. Overall these data suggest that PDF inhibitors are an interesting new class of antimicrobial worthy of further investigation in the treatment of respiratory tract and skin infections.

Bacterial contamination of surgical gloves by water droplets spilt after scrubbing.

Wound infection and deep sepsis can have disastrous consequences, particularly in orthopaedic surgery. Strict protocols, ultra-clean air, prophylactic antibiotics, and impervious gowns and drapes, have all been shown to diminish wound infection. However it remains a common and significant problem. The water droplets spilt from the surgeons hands after meticulous scrubbing with povidone iodine were cultured. The permeability of the surgical glove packaging to Gram-positive bacteria was also investigated. The water droplets from the surgeon's arms contained environmental and potentially pathogenic bacteria including a micrococcus, a coliform and coagulase-negative staphylococci. The paper packaging for the range of sterile surgical gloves tested was discovered to be permeable to Gram-positive bacteria. In conclusion accidental water droplet contamination of surgical gloves is a potential source of infection. Alternative recommendations are made.

Bacterial strike-through of re-usable surgical drapes: the effect of different wetting agents.

Wound contamination and the resultant postoperative infection is a major problem in all forms of surgery. Air contamination, gloves, surgical instruments and drapes have all been investigated as sources of wound contamination. We investigated the effect of different wetting agents on strike-through rate of bacteria through re-usable polyester/cotton surgical drapes using a newly described method. Within 30 min bacterial strike-through of dry surgical drapes occurs. Wetting drapes with blood or normal saline enhances the strike-through rate of bacteria. Wetting drapes with iodine or chlorhexidine diminishes, but does not stop, bacterial strike-through. The use of re-usable polyester/cotton drapes is a potential source of wound contamination especially when wetted with blood or normal saline.

Effect of jewellery on surface bacterial counts of operating theatres.

Twenty items of three jewellery types were studied. Finger rings, nose and ear piercings increased local surface bacterial counts when in situ, and especially after removal (P<0.0001). Although in the UK the National Association of Theatre Nurses' guidelines suggest that all jewellery should be removed before scrubbing, we suggest that jewellery worn on noses and ears should be left in situ and covered by masks and hats, respectively. The effect of jewellery on skin disinfection needs further study before guidelines can be made concerning finger rings.

Direct measurement of bacterial penetration through surgical gowns: a new method.

There is a paucity of data on the penetration of bacteria through surgical gowns during operations. A simple new method was developed, using Petri dishes filled with horse blood agar that were attached to the outside of the gown material. This was used to assess bacterial penetration through disposable spun-bonded polyester gowns and re-usable woven polyester gowns during normal use. There was a significant difference between the two gown types when tested in the axilla (P = 0.02), the groin (P = 0.02) and the peri-anal region (P < 0.01), with the disposable gowns performing to a higher standard. Re-usable gowns demonstrated variation in penetrability, and for this reason, may be unsuitable for use in orthopaedic implant surgery.