Objective To characterise failure of antibiotic treatment in primary care in the United Kingdom in four common infection classes from 1991 to 2012.Design Longitudinal analysis of failure rates for first line antibiotic monotherapies associated with diagnoses for upper and lower respiratory tract infections, skin and soft tissue infections, and acute otitis media. Setting Routine primary care data from the UK Clinical Practice Research Datalink (CPRD).Main outcome measures Adjusted rates of treatment failure defined by standardised criteria and indexed to year 1 (1991=100).Results From 58 million antibiotic prescriptions in CPRD, we analysed 10 967 607 monotherapy episodes for the four indications: 4 236 574 (38.6%) for upper respiratory tract infections; 3 148 947 (28.7%) for lower respiratory tract infections; 2 568 230 (23.4%) for skin and soft tissue infections; and 1 013 856 (9.2%) for acute otitis media. In 1991, the overall failure rate was 13.9% (12.0% for upper respiratory tract infections; 16.9% for lower respiratory tract infections; 12.8% for skin and soft tissue infections; and 13.9% for acute otitis media). By 2012, the overall failure rate was 15.4%, representing an increase of 12% compared with 1991 (adjusted value indexed to first year (1991) 112, 95% confidence interval 112 to 113). The highest rate was seen in lower respiratory tract infections (135, 134 to 136). While failure rates were below 20% for most commonly prescribed antibiotics (amoxicillin, phenoxymethylpenicillin (penicillin-V), and flucloxacillin), notable increases were seen for trimethoprim in the treatment of upper respiratory tract infections (from 29.2% in 1991-95 to 70.1% in 2008-12) and for ciprofloxacin (from 22.3% in 1991-95 to 30.8% in 2008-12) and cefalexin (from 22.0% in 1991-95 to 30.8% in 2008-12) in the treatment of lower respiratory tract infections. Failure rates for broad spectrum penicillins, macrolides, and flucloxacillin remained largely stable.Conclusions From 1991 to 2012, more than one in 10 first line antibiotic monotherapies for the selected infections were associated with treatment failure. Overall failure rates increased by 12% over this period, with most of the increase occurring in more recent years, when antibiotic prescribing in primary care plateaued and then increased.

Urinary follicle stimulating hormone (FSH) is being used for the treatment of human infertility. Recently, FSH manufactured by means of recombinant DNA technology with a much higher purity (> 99%) has become available. A prospective, randomized, assessor-blind, multicentre (n = 18) study was conducted in infertile women undergoing in-vitro fertilization comparing recombinant FSH (Org 32489, Puregon) and urinary FSH (Metrodin). Eligible subjects were randomized (recombinant versus urinary FSH = 3:2) and pretreated with buserelin for pituitary suppression. FSH was given until three or more follicles with a diameter of at least 17 mm were seen. After oocyte retrieval, fertilization routines were applied according to local procedures. No more than three embryos were replaced. In all, 585 subjects received recombinant FSH and 396 urinary FSH. Significantly more oocytes were retrieved after recombinant FSH treatment (mean adjusted for centre 10.84 versus 8.95, P < 0.0001). Ongoing pregnancy rates per attempt and transfer in the recombinant FSH group were 22.17 and 25.97% respectively, and in the urinary FSH group, 18.22 and 22.02% respectively (not significant). Ongoing pregnancy rates including pregnancies resulting from frozen-thawed embryo cycles were 25.7% for recombinant and 20.4% for urinary FSH (P = 0.05). Compared to urinary FSH, the total dose of FSH was significantly lower with recombinant FSH (2138 versus 2385 IU, P < 0.0001) in a significantly shorter treatment period (10.7 versus 11.3 days, P < 0.0001). No clinically relevant differences between recombinant and urinary FSH were seen with respect to safety variables. It is concluded that recombinant FSH (Puregon) is more effective than urinary FSH in inducing multifollicular development and achieving an ongoing pregnancy.

The aim of this systematic review and meta-analysis was to conduct a comprehensive assessment of the evidence on the efficacy and safety of oral dydrogesterone versus micronized vaginal progesterone (MVP) for luteal phase support. Embase and MEDLINE were searched for studies that evaluated the effect of luteal phase support with daily administration of oral dydrogesterone (20 to 40 mg) versus MVP capsules (600 to 800 mg) or gel (90 mg) on pregnancy or live birth rates in women undergoing fresh-cycle IVF (protocol registered at PROSPERO [CRD42018105949]). Individual participant data (IPD) were extracted for the primary analysis where available and aggregate data were extracted for the secondary analysis. Nine studies were eligible for inclusion; two studies had suitable IPD (full analysis sample: n = 1957). In the meta-analysis of IPD, oral dydrogesterone was associated with a significantly higher chance of ongoing pregnancy at 12 weeks of gestation (odds ratio [OR], 1.32; 95% confidence interval [CI], 1.08 to 1.61; P = 0.0075) and live birth (OR, 1.28; 95% CI, 1.04 to 1.57; P = 0.0214) compared to MVP. A meta-analysis combining IPD and aggregate data for all nine studies also demonstrated a statistically significant difference between oral dydrogesterone and MVP (pregnancy: OR, 1.16; 95% CI, 1.01 to 1.34; P = 0.04; live birth: OR, 1.19; 95% CI, 1.03 to 1.38; P = 0.02). Safety parameters were similar between the two groups. Collectively, this study indicates that a higher pregnancy rate and live birth rate may be obtained in women receiving oral dydrogesterone versus MVP for luteal phase support.

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