Longitudinal evaluation of azithromycin and cytokine concentrations in amniotic fluid following one‐time oral dosing in pregnancy

To utilize noninvasive collection of amniotic fluid in the setting of preterm premature rupture of membranes (PPROMs) to report the time concentration profile of azithromycin in amniotic fluid over 7 days from a single dose, and evaluate the correlation between azithromycin concentration and inflammatory markers in amniotic fluid. Prospective cohort study of five pregnant patients admitted with PPROMs and treated with a single 1 g oral azithromycin dose. Amniotic fluid was collected from pads and used to quantify azithromycin concentration as well as TNFa, IL‐1a, IL‐1b, IL‐6, IL‐8, and IL‐10 concentrations. Primary outcome was time/concentration profile of azithromycin in amniotic fluid. Secondary outcome included correlation between azithromycin concentration and cytokine concentrations. Five patients were enrolled. Mean gestational age on admission with PPROM was 27.5 ± 2.3 weeks with a median latency of 7 days (interquartile range [IQR] = 4–13). A median of two samples/day (IQR = 1–3) were collected per participant. Azithromycin was quantified in duplicate; intra‐assay coefficient of variation was 17%. Azithromycin concentration was less than 60 ng/ml after day 3. Azithromycin concentration was positively correlated with IL‐8 (r = 0.38, p = 0.03), IL1a (r = 0.39, p = 0.03), and IL‐1b (r = 0.36, p = 0.04) in amniotic fluid. Azithromycin is detectable in amniotic fluid over 7 days from a single 1 g maternal dose, however, it is not sustained over the range of minimum inhibitory concentration for common genitourinary flora. Based on correlation with specific cytokines, azithromycin penetration in amniotic fluid may relate to maternal monocyte concentration in amniotic fluid in the setting of PPROM.

Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

Azithromycin is used to prevent infection in setting of preterm premature rupture of membranes (PPROMs), but there is no established dose. One cross‐sectional study with one patient found amniotic fluid azithromycin concentration was below minimum inhibitory concentration (MIC)50 of common genitourinary (GU) flora 7 days after a single 1 g maternal dose. There is no reported correlation between maternal azithromycin treatment and the concentration of drug and inflammatory cytokines in amniotic fluid.

• WHAT QUESTIONS DID THIS STUDY ADDRESS?

Our objective was to utilize noninvasive collection of amniotic fluid in pregnant patients admitted with PPROM to address whether one‐time maternal dosing of azithromycin can produce a sustained amniotic fluid concentration greater than the MIC of common GU flora over 7 days, and secondarily, whether amniotic fluid azithromycin concentration was correlated with inflammatory cytokine concentrations.

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

Azithromycin is detectable in amniotic fluid over 7 days from a single 1 g maternal dose, however, it is not sustained over the range of MIC for common GU flora. Azithromycin concentration in amniotic fluid is correlated with specific cytokines that suggest that azithromycin penetration in amniotic fluid may relate to maternal monocyte concentration in amniotic fluid in the setting of PPROM.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

Amniotic fluid may be collected noninvasively from patients with PPROM and used to evaluate the fetal environment, including medication penetrance and inflammatory markers. Given the benefit of maternal and fetal exposure to azithromycin for prevention of adverse perinatal outcomes, it is important to study how maternal dosing leads to azithromycin concentration within the maternal fetal unit in order to optimize therapy.     

Development of technologies for placement of perineural catheters

Continuous peripheral nerve block (CPNB) success is largely dependent on placement of the catheter close enough to the nerve to allow effective and sustained analgesia following painful surgeries with a minimum volume of local anesthetic. One of the most common problems associated with CPNB involves accurate placement of the catheter tip, migration, and dislodgement of the catheter. This is of increasing importance now that catheters are left in place for prolonged periods of time to provide postoperative analgesia, and patients with peripheral nerve catheters are being discharged home with ambulatory pumps. In response to the challenges of providing safe, effective, and consistently reliable analgesia, research and development in this field is expanding rapidly. This review article presents results from recent publications addressing the subject of peripheral nerve catheter localization.     

Infrapatellar fat pad volume and Hoffa-synovitis after ACL reconstruction: Association with early osteoarthritis features and pain over 5 years

Infrapatellar fat pad (IPFP) morphology and Hoffa-synovitis may be relevant to the development and progression of post-traumatic osteoarthritis (OA). We aimed to compare IPFP volume and Hoffa-synovitis in participants with anterior cruciate ligament reconstruction (ACLR) and uninjured controls, and to determine their association with prevalent and worsening early knee OA features and pain in participants post-ACLR. We assessed IPFP volume and Hoffa-synovitis from magnetic resonance imaging (MRI) in 111 participants 1-year post-ACLR and 20 uninjured controls. Patellofemoral and tibiofemoral cartilage and bone marrow lesions (BMLs) were assessed from MRIs at 1 and 5 years post-ACLR, and worsening defined as any longitudinal increase in lesion size/severity. IPFP volume and Hoffa-synovitis prevalence were compared between groups with analysis of covariance and χ ² tests, respectively. Generalized linear models assessed the relation of IPFP volume and Hoffa-synovitis to prevalent and worsening features of OA and knee pain (Knee injury and Osteoarthritis Outcome Score—Pain Subscale, Anterior Knee Pain Scale). No significant between-group differences were observed in IPFP volume (ACLR 34.39 ± 7.29cm³, Control 34.27 ± 7.56cm³) and Hoffa-synovitis (ACLR 61%, Control 80%). Greater IPFP volume at 1-year post-ACLR was associated with greater odds of patellofemoral BMLs at 1-year (odds ratio [OR] [95% confidence intervals]: 1.104 [1.016, 1.200]) and worsening tibiofemoral cartilage lesions at 5-year post-ACLR (OR: 1.234 [1.026, 1.483]). Hoffa-synovitis at 1-year post-ACLR was associated with greater odds of worsening patellofemoral BMLs at 5-year post-ACLR (OR: 7.465 [1.291, 43.169]). In conclusion, IPFP volume and Hoffa-synovitis prevalence are similar between individuals 1-year post-ACLR and controls. Greater IPFP volume and Hoffa-synovitis appear to be associated with the presence and worsening of some early OA features in those post-ACLR, but not pain.     

Application of principal component and hierarchical cluster analysis to classify fruits and vegetables commonly consumed in Ireland based on in vitro antioxidant activity

The purpose of this study was to gain insights into the variations in antioxidant profiles between fruits and vegetables using pattern recognition tools; classification was achieved based on global antioxidant activity, levels of antioxidant groups (total phenolics, total anthocyanins, ascorbic acid) and quality parameters (instrumental colour, moisture). Six vegetables (broccoli, carrot [organic and intensively grown], butterhead lettuce, red onion, yellow onion) and eight fruits (blueberries, cherry tomato, cranberries, red grapes, green pepper, raspberry, red pepper and strawberry) commonly consumed in Ireland were analysed. Antioxidant activity (ARP) and concentrations of bioactive compound groups differed according to sample type. Berry fruits had the highest antioxidant activity (1.51-2.97 (g/L)⁻¹). By contrast, vegetables were quite low in antioxidant activity (0.14-0.39 (g/L)⁻¹). Interrelationships between the parameters analysed and the different fruits and vegetables were investigated by principal component analysis (PCA) and hierarchical cluster analysis (HCA). PCA revealed that the first two components represented 62% of the total variability in antioxidant activity and different antioxidant groups. HCA classified samples into four main groups on the basis of the measured parameters.