Hair mercury concentrations and in vitro fertilization (IVF) outcomes among women from a fertility clinic

Total hair mercury (Hg) was measured among 205 women undergoing in vitro fertilization (IVF) treatment and the association with prospectively collected IVF outcomes (229 IVF cycles) was evaluated. Hair Hg levels (median = 0.62 ppm, range: 0.03–5.66 ppm) correlated with fish intake (r = 0.59), and exceeded the recommended EPA reference of 1 ppm in 33% of women. Generalized linear mixed models with random intercepts accounting for within-woman correlations across treatment cycles were used to evaluate the association of hair Hg with IVF outcomes adjusted for age, body mass index, race, smoking status, infertility diagnosis, and protocol type. Hair Hg levels were not related to ovarian stimulation outcomes (peak estradiol levels, total and mature oocyte yields) or to fertilization rate, embryo quality, clinical pregnancy rate or live birth rate.     

Placental concentrations of mercury,lead, cadmium,and arsenic and the risk of neural tube defects in a Chinese population

To examine whether in utero exposure to mercury (Hg), cadmium (Cd), lead (Pb) and arsenic (As) is associated with an elevated neural tube defects (NTDs) risk, placental concentrations of total Hg, Cd, Pb and As were measured with an inductively coupled plasma mass spectrometer (ICP-MS) in 36 anencephaly and 44 spina bifida cases as well as in 50 healthy controls. The median Hg concentration in the NTD cases (2.25 ng/g) was higher than that of the controls (1.16 ng/g). The odds ratio (OR) for an Hg concentration above the median was 8.80 (95% CI 3.80–20.36) for the NTD cases. NTD risks increased for the second and third high levels of the concentrations, with ORs of 2.70 (95% CI 1.13–6.43) and 18.20 (95% CI 5.45–60.73), respectively. Therefore, higher placental levels of Hg are associated with an elevated risk of NTDs.     

Lead,mercury, and cadmium in blood and their relation to diet among Swedish adults

The aim of the present study was to examine the body burden of lead (Pb), mercury (Hg), and cadmium (Cd) in blood among Swedish adults and the association between blood levels, diet and other lifestyle factors.The study was based on a subgroup (n = 273) of the national survey Riksmaten 2010–2011 (4-day food records and questionnaire). Lead, Hg, and Cd were measured in whole blood, and Cd additionally in urine, by mass or fluorescence spectrometry methods.The median values (5–95th percentiles) of the metals in blood were as follows; Pb: 13.4 (5.8–28.6) μg/L, Hg: 1.13 (0.31–3.45) μg/L, and Cd: 0.19 (0.09–1.08) μg/L. All three metals increased with increasing age. Lead levels in blood were positively associated with intakes of game and alcohol, Hg was related to fish intake, and blood Cd related to smoking and low iron stores and to a low meat intake.Body burdens of the studied metals were generally below health based reference values, but several individuals had blood Pb levels above the reference point for possible nephrotoxic and developmental neurotoxic effects. As health effects cannot be excluded, individuals with high Pb exposure should aim at decreasing their body burden, both from food and from other exposure routes.     

Markers of oxidative stress in follicular fluid of women with endometriosis and tubal infertility undergoing IVF

Oxidative stress and trace elements in the oocytes environment is explored in endometriosis and impact on in vitro fertilization (IVF) outcome assessed. Follicular fluid was aspirated at the time of oocyte retrieval from endometriosis (n = 200) and tubal infertility (n = 140) and the analytes measured using spectroscopy and HPLC. Increased concentration of reactive oxygen species (ROS), nitric oxide (NO), lipid peroxidation (LPO), iron, lead, cadmium and reduced levels of total antioxidant capacity (TAC), superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione reductase (GR), vitamins A, C, E, copper, zinc and selenium was observed compared to tubal infertility. Increased ROS and NO in endometriosis and tubal infertility associated with poor oocytes and embryo quality. Increased levels of ROS, NO, LPO, cadmium and lead were observed in women who did not become pregnant compared to women who did. Intrafollicular zinc levels were higher in women with endometriosis who subsequently became pregnant following IVF.     

Associations between paternal urinary phthalate metabolite concentrations and reproductive outcomes among couples seeking fertility treatment

IntroductionLimited evidence suggests that male exposure to ubiquitous environmental phthalates may result in poor reproductive outcomes among female partners.MethodsThis analysis included male–female couples undergoing in vitro fertilization (IVF) and/or intrauterine insemination (IUI). We evaluated associations between the geometric mean of paternal specific gravity-adjusted urinary phthalate concentrations prior to the female partners’ cycle and fertilization, embryo quality, implantation, and live birth using generalized linear mixed models.ResultsTwo-hundred eighteen couples underwent 211 IVF and 195 IUI cycles. Trends were observed between paternal urinary mono-3-carboxypropyl phthalate (MCPP; P = 0.01) and mono(carboxyoctyl) phthalate (MCOP; P = 0.01) and decreased odds of implantation. MCPP and MCOP were also associated with decreased odds of live birth following IVF (P = 0.01 and P = 0.04, respectively), and monobutyl phthalate above the first quartile was significantly associated with decreased odds of live birth following IUI (P = 0.04). However, most urinary phthalate metabolites were not associated with these reproductive outcomes.ConclusionSelected phthalates were associated with decreased odds of implantation and live birth.     

Visceral sensitivity,anxiety, and smoking among treatment-seeking smokers

It is widely recognized that smoking is related to abdominal pain and discomfort, as well as gastrointestinal disorders. Research has shown that visceral sensitivity, experiencing anxiety around gastrointestinal sensations, is associated with poorer gastrointestinal health and related health outcomes. Visceral sensitivity also increases anxiety symptoms and mediates the relation with other risk factors, including gastrointestinal distress. No work to date, however, has evaluated visceral sensitivity in the context of smoking despite the strong association between smoking and poor physical and mental health. The current study sought to examine visceral sensitivity as a unique predictor of cigarette dependence, threat-related smoking abstinence expectancies (somatic symptoms and harmful consequences), and perceived barriers for cessation via anxiety symptoms. Eighty-four treatment seeking adult daily smokers (M_age = 45.1 years [SD = 10.4]; 71.6% male) participated in this study. There was a statistically significant indirect effect of visceral sensitivity via general anxiety symptoms on cigarette dependence (b = 0.02, SE = 0.01, Bootstrapped 95% CI [0.006, 0.05]), smoking abstinence somatic expectancies (b = 0.10, SE = 0.03, Bootstrapped 95% CI [0.03, 0.19]), smoking abstinence harmful experiences (b = 0.13, SE = 0.05, Bootstrapped 95% CI [0.03, 0.25]), and barriers to cessation (b = 0.05, SE = 0.06, Bootstrapped 95% CI [0.01, 0.13]). Overall, the present study serves as an initial investigation into the nature of the associations between visceral sensitivity, anxiety symptoms, and clinically significant smoking processes among treatment-seeking smokers. Future work is needed to explore the extent to which anxiety accounts for relations between visceral sensitivity and other smoking processes (e.g., withdrawal, cessation outcome).     

Evaluation of urinary metal concentrations and sperm DNA damage in infertile men from an infertility clinic

This study aimed to examine associations between urinary metal concentrations and sperm DNA damage. Thirteen metals [arsenic (As), cadmium (Cd), cobalt (Co), chromium (Cr), copper (Cu), iron (Fe), lead (Pb), manganese (Mn), molybdenum (Mo), mercury (Hg), nickel (Ni), selenium (Se), and zinc (Zn)] were detected in urine samples of 207 infertile men from an infertility clinic using inductively coupled plasma mass spectrometry, and also, sperm DNA damage (tail length, percent DNA tail, and tail distributed moment) were assessed using neutral comet assay. We found that urinary Hg and Ni were associated with increasing trends for tail length (both p for trend < 0.05), and that urinary Mn was associated with increasing trend for tail distributed moment (p for trend = 0.02). These associations did persist even when considering multiple metals. Our results suggest that environmental exposure to Hg, Mn, and Ni may be associated with increased sperm DNA damage.     

Toxic trace metals and embryo quality indicators during in vitro fertilization (IVF)

Trace exposures to the toxic metals mercury (Hg), cadmium (Cd) and lead (Pb) may interfere with in vitro fertilization (IVF). The aim of this study is to explore biologically plausible hypotheses concerning associations between metals and embryo quality indicators during IVF. For 24 female patients, a multivariable ordinal logistic regression model suggests a 75% reduction in the odds for higher embryo cell cleavage per μg/dL increase in blood Pb (adjusted odds ratio (aOR) 0.25, 95% confidence interval (CI) 0.07-0.86). For 15 male partners, each μg/L increase in blood Hg (aOR 0.60, 95% CI 0.45-0.79) and μg/dL increase in blood Pb (aOR 0.58, 95% CI 0.37-0.91) is associated with a decrease in the analogous odds. Embryo fragmentation is reduced by higher blood Hg (aOR 0.85, 95% CI 0.72-1.00), but increased by higher blood Pb (aOR 1.47, 95% CI 1.11-1.94) in men. The magnitude of these suggested effects warrants confirmation in a larger study.     

Alteration in bone geometric and mechanical properties,histomorphometrical parameters of trabecular bone,articular cartilage,and growth plate in adolescent rats after chronic co-exposure to cadmium and lead in the case of supplementation with green,black, red and white tea

Adolescent male Wistar rats were used to check whether regular consumption of black, red, white, or green tea would have a protective effect on femur development during 12-week exposure to Cd and Pb (7 mg Cd and 50 mg Pb in 1 kg of the diet). The animals were randomly divided (n = 12) into a positive control (without Cd, Pb and teas), a negative control group (Cd and Pb), and groups supplemented additionally with green (GT), black (BT), red (RT), and white tea (WT). Heavy metals reduced the geometric and densitometric parameters and the total thickness of articular cartilage irrespective of tea administration and influenced mechanical endurance, growth plate thickness, and trabecular histomorphometry depending on the tea type. It is difficult to indicate which tea has the best protective effects on bone and hyaline cartilage against heavy metal action.     

Statins in prevention of repeat revascularization after percutaneous coronary intervention—A meta-analysis of randomized clinical trials

Recent prospective cohort studies have shown that patients discharged on statins after percutaneous coronary intervention (PCI) are at lower risks of repeat revascularization and mortality when compared to those not on statins after discharge. However, few randomized clinical trials among post-PCI patients confirmed these beneficial effects. It is needed to evaluate the effects of post-procedural statin therapy on individual clinical outcomes to facilitate the further investigation on identifying the underlying mechanism(s). A meta-analysis of randomized clinical trials was conducted to examine the effects of statin therapy initiated after coronary angioplasty on repeat revascularization, all-cause mortality and myocardial infarction (MI). From relevant reports on Medline (from inception to October 2009), six randomized clinical trials comprising 2979 patients were included. Relative risks were evaluated for pooled data via random effect models. Compared with controls, post-PCI statin therapy was associated with a significantly decreased risk of repeat revascularization (risk ratio (RR) = 0.73, 95% confidence interval (CI), 0.55–0.98, p = 0.04), nonsignificantly decreased risks of all-cause mortality (RR = 0.88, 95% CI, 0.35–2.21, p = 0.79), MI (RR = 0.76, 95% CI, 0.49–1.18, p = 0.23), and target lesion or target vessel revascularization (RR = 0.58, 95% CI, 0.24–1.39, p = 0.22). In conclusion, statin therapy after PCI can reduce the risk of repeat revascularization. Further investigation is needed to identify the underlying mechanism(s).     

Essential trace and toxic element concentrations in organic and conventional milk in NW Spain

Dietary composition and husbandry practices largely determine essential trace element status and toxic element exposure of livestock, and consequently their concentrations in animal products. This study evaluates the main essential trace (Co, Cr, Cu, Fe, I, Mn, Mo, Ni, Se and Zn) and toxic (As, Cd, Hg and Pb) element concentrations in milk from organic and conventional farms in NW Spain (n = 50). Milk samples were acid digested and analyzed by ICP-MS. Essential trace element concentrations in organic milk were significantly lower compared to conventional milk, this was especially evident for elements that are routinely supplemented at high concentrations in the conventional concentrate feed: Cu (41.0 and 68.9 μg/L in organic and conventional milk, respectively), Zn (3326 and 3933 μg/L), I (78 and 265 μg/L) and Se (9.4 and 19.2 μg/L). Toxic metal concentrations in milk were in general very low and no statistically significant differences were observed between organic and conventional milk. In addition, the mineral content of organic milk showed a seasonal pattern, the significantly higher As (65%) and Fe (13%) concentrations found in the winter sampling possibly being related to a higher consumption of concentration feed and soil ingestion when grazing.     

Linezolid versus vancomycin for the treatment of Gram-positive bacterial infections: meta-analysis of randomised controlled trials

This review aimed to compare data regarding the effectiveness and safety of linezolid and vancomycin in the treatment of Gram-positive bacterial infections. PubMed and other databases were searched to identify relevant randomised controlled trials (RCTs). Nine RCTs studying 2489 clinically assessed patients were included in the meta-analysis. Overall, there was no difference between linezolid and vancomycin regarding treatment success in clinically assessed patients [odds ratio (OR) = 1.22, 95% confidence interval (CI) 0.99–1.50]. Linezolid was more effective than vancomycin in patients with skin and soft-tissue infections (OR = 1.40, 95% CI 1.01–1.95). However, there was no difference in treatment success for patients with bacteraemia (OR = 0.88, 95% CI 0.49–1.58) or pneumonia (OR = 1.16, 95% CI 0.85–1.57). Linezolid was associated with better eradication rates in all microbiologically assessed patients compared with vancomycin (OR = 1.33, 95% CI 1.03–1.71). There was no difference in total adverse effects possibly or probably related to the study drugs (OR = 1.14, 95% CI 0.82–1.59). However, nephrotoxicity was recorded more commonly in patients receiving vancomycin (OR = 0.31, 95% CI 0.13–0.74). In conclusion, linezolid is as effective as vancomycin in patients with Gram-positive infections. There is superior clinical and microbiological outcome with linezolid in complicated skin and soft-tissue infections caused by Staphylococcus aureus.     

Colistin therapy for microbiologically documented multidrug-resistant Gram-negative bacterial infections: a retrospective cohort study of 258 patients

It is unclear whether the effectiveness of polymyxins depends on the site of infection, the responsible pathogen, dosage, and monotherapy vs. combination therapy. We investigated colistin therapy in a large, retrospective, single-centre, cohort study. Primary analysis outcomes were infection outcome, survival and nephrotoxicity. Over a 7-year period (October 2000 to October 2007), 258 patients received intravenous (i.v.) colistin for at least 72 h for microbiologically documented multidrug-resistant Gram-negative bacterial infections, comprising 170 (65.9%) Acinetobacter baumannii, 68 (26.4%) Pseudomonas aeruginosa, 18 (7.0%) Klebsiella pneumoniae, 1 (0.4%) Stenotrophomonas maltophilia and 1 (0.4%) Enterobacter cloacae. Cure of infection occurred in 79.1% of patients, nephrotoxicity in 10% and hospital survival in 65.1%. In the multivariate analysis, independent predictors of survival were colistin average daily dose [adjusted odds ratio (aOR) = 1.22, 95% confidence interval (CI) 1.05–1.42] and cure of infection (aOR = 9, 95% CI 3.6–23.1), whilst the proportion of creatinine change (aOR = 0.21, 95% CI 0.1–0.45), Acute Physiology and Chronic Health Evaluation (APACHE) II score (aOR = 0.89, 95% CI 0.84–0.95) and haematological disease (aOR = 0.23, 95% CI 0.08–0.66) were associated with mortality. Effectiveness of colistin was not dependent on the type of pathogen. No independent predictors for nephrotoxicity were observed. The findings of the largest cohort study to date on i.v. colistin show that colistin is a valuable antibiotic with acceptable nephrotoxicity and considerable effectiveness that depends on the daily dosage and infection site.     

Intersecting epidemics of HIV,HCV, and syphilis among soon-to-be released prisoners in Kyrgyzstan: Implications for prevention and treatment

BackgroundCentral Asia is afflicted with increasing HIV incidence, low antiretroviral therapy (ART) coverage and increasing AIDS mortality, driven primarily by people who inject drugs (PWID). Reliable data about HIV, other infectious diseases, and substance use disorders in prisoners in this region is lacking and could provide important insights into how to improve HIV prevention and treatment efforts in the region.MethodsA randomly sampled, nationwide biobehavioural health survey was conducted in 8 prisons in Kyrgyzstan among all soon-to-be-released prisoners; women were oversampled. Consented participants underwent computer-assisted, standardized behavioural health assessment surveys and testing for HIV, HCV, HBV, and syphilis. Prevalence and means were computed, and generalized linear modelling was conducted, with all analyses using weights to account for disproportionate sampling by strata.ResultsAmong 381 prisoners who underwent consent procedures, 368 (96.6%) were enrolled in the study. Women were significantly older than men (40.6 vs. 36.5; p = 0.004). Weighted prevalence (%), with confidence interval (CI), for each infection was high: HCV (49.7%; CI: 44.8–54.6%), syphilis (19.2%; CI: 15.1–23.5%), HIV (10.3%; CI: 6.9–13.8%), and HBV (6.2%; CI: 3.6–8.9%). Among the 31 people with HIV, 46.5% were aware of being HIV-infected. Men, compared to women, were significantly more likely to have injected drugs (38.3% vs.16.0%; p = 0.001). Pre-incarceration and within-prison drug injection, primarily of opioids, was 35.4% and 30.8%, respectively. Independent correlates of HIV infection included lifetime drug injection (adjusted odds ratio [AOR] = 38.75; p = 0.001), mean number of years injecting (AOR = 0.93; p = 0.018), mean number of days experiencing drug problems (AOR = 1.09; p = 0.025), increasing duration of imprisonment (AOR = 1.08; p = 0.02 for each year) and having syphilis (AOR = 3.51; p = 0.003), while being female (AOR = 3.06; p = 0.004) and being a recidivist offender (AOR = 2.67; p = 0.008) were independently correlated with syphilis infection.ConclusionDrug injection, syphilis co-infection, and exposure to increased risk during incarceration are likely to be important contributors to HIV transmission among prisoners in Kyrgyzstan. Compared to the community, HIV is concentrated 34-fold higher in prisoners. A high proportion of undiagnosed syphilis and HIV infections presents a significant gap in the HIV care continuum. Findings highlight the critical importance of evidence-based responses within prison, including enhanced testing for HIV and sexually transmitted infections, to stem the evolving HIV epidemic in the region.     

Prenatal exposure to lead in relation to risk of preterm low birth weight: A matched case–control study in China

We investigated the association between prenatal exposure to lead (Pb) and the risk of preterm low birth weight (PLBW). Pb concentrations in maternal urine collected at birth from 408 subjects (102 cases and 306 matched controls) were analyzed and adjusted by creatinine. The median Pb concentration in the PLBW cases (10.60 μg Pb/g creatinine) was higher than that of the controls (7.28 μg Pb/g creatinine). An adjusted odds ratio (OR) of 2.96 (95% CI = 1.49–5.87) for PLBW was observed when the highest tertile was compared to the lowest tertile of Pb levels. The association was more pronounced among female infants (adjusted OR = 3.67 for the highest tertile; 95% CI = 1.35–9.93) than male infants (adjusted OR = 1.91 for the highest tertile; 95% CI = 0.74–4.95). Our study suggests that prenatal exposure to levels of Pb encountered today in China is associated with an elevated risk of PLBW.     

Changes in plasma levels of asymmetric dimethylarginine,symmetric dimethylarginine,and arginine after a single dose of vardenafil in patients with pulmonary hypertension

ObjectiveWe investigated whether vardenafil, a phosphodiesterase-5 inhibitor, alters plasma levels of asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and arginine.Patients and methodsADMA, SDMA, and arginine were measured (0–540 min) in 12 patients with pulmonary hypertension after a single oral dose of vardenafil. Invasive hemodynamic data were collected at baseline and after 60 min.ResultsA reduction in ADMA was observed at 30 and 45 min with a median change of − 11.1% (P = 0.021) and − 12.5% (P = 0.002). SDMA decreased with a median − 5.3% change (P = 0.032) at 45 min. An increase in arginine, median 40.3% (P = 0.002), 45.0% (P = 0.010), and 77.1% (P = 0.008) was observed at 120, 300, and 540 min respectively. An increase in the arginine/ADMA ratio, median 11.7% (P = 0.012), 32.5% (P = 0.003), 26.5% (P = 0.021), 33% (P = 0.007), 48.5% (P = 0.007), and 63.1% (P = 0.008) was observed at 15, 45, 60, 120, 300, and 540 min respectively. There was a positive correlation between vardenafil exposure and the percent change in the arginine/ADMA ratio from baseline to 540 min (r = 0.80; P = 0.01). A correlation between baseline mean right atrial pressure (mRAP) and baseline ADMA (r = 0.65; P = 0.023), and baseline SDMA (r = 0.61; P = 0.035) was observed. A correlation between the baseline arginine/ADMA ratio and baseline cardiac output (CO) (r = 0.59; P = 0.045) and baseline cardiac index (CI) (r = 0.61; P = 0.036) was observed. Baseline arginine/ADMA ratio correlated with baseline mRAP (r = − 0.79; P = 0.002). A correlation between change (0–60 min) in CI and change in arginine (r = 0.77; P = 0.003) as well as change in the arginine/ADMA ratio (r = 0.61; P = 0.037) was observed.ConclusionsVardenafil induced changes in ADMA, SDMA, arginine, and the arginine/ADMA ratio in patients with PH. An increase in arginine and the arginine/ADMA ratio was associated with improvement in CI.     

History of abuse and risky sex among substance users: The role of rejection sensitivity and the need to belong

This study investigates abuse and rejection sensitivity as important correlates of risky sexual behavior in the context of substance use. Victims of abuse may experience heightened sensitivity to acute social rejection and consequently engage in risky sexual behavior in an attempt to restore belonging. Data were collected from 258 patients at a substance use treatment facility in Washington, D.C. Participants' history of abuse and risky sexual behavior were assessed via self-report. To test the mediating role of rejection sensitivity, participants completed a social rejection task (Cyberball) and responded to a questionnaire assessing their reaction to the rejection experience. General risk-taking propensity was assessed using a computerized lab measure. Abuse was associated with increased rejection sensitivity (B = 0.124, SE = 0.040, p = 0.002), which was in turn associated with increased risky sex (B = 0.06, SE = 0.028, p = 0.03) (indirect effect = 0.0075, SE = 0.0043; 95% CI [0.0006, 0.0178]), but not with other indices of risk-taking. These findings suggest that rejection sensitivity may be an important mechanism underlying the relationship between abuse and risky sexual behavior among substance users. These effects do not extend to other risk behaviors, supporting the notion that risky sex associated with abuse represents a means to interpersonal connection rather than a general tendency toward self-defeating behavior.     

Continuous versus intermittent infusion of cefepime in neurosurgical patients with post-operative intracranial infections

Cefepime is administered as an intermittent infusion (II); however, continuous infusion (CI) may be advantageous because β-lactam antibiotics exhibit time-dependent antibacterial activity. This retrospective, non-randomised, comparative study included 68 neurosurgical patients with post-operative intracranial infections treated with 4 g/day cefepime over 24 h as a CI (n = 34) or 2 g every 12 h as II (n = 34). CI controlled the intracranial infection more rapidly and effectively than II (6.6 ± 1.9 days vs. 7.8 ± 2.6 days; P = 0.036). By considering the minimum inhibitory concentrations (MICs) to be 4 μg/mL and 8 μg/mL, the percentage of time when the cefepime plasma or CSF concentrations were higher than the MIC (%T_>MIC) was calculated for each patient. For plasma cefepime concentrations, the %T_>MIC in the CI group was higher than in the II group (for MICs of 8 μg/mL, 100% vs. 75%, respectively). The mean calculated area under the curve (AUC) in the CI group was similar to the II group (1197.99 ± 72.15 μg h/mL vs. 890.84 ± 140.78 μg h/mL; P = 0.655). For CSF cefepime concentrations, the %T_>MIC in the CI group was higher than in the II group (for MICs of 4 μg/mL and 8 μg/mL, 83.3% and 75% vs. 25% and 0%, respectively). The mean calculated AUC for the CI group was higher than the II group (220.56 ± 13.59 μg h/mL vs. 86.34 ± 5.69 μg h/mL; P = 0.003). Therefore, CI of cefepime significantly enhanced the antibacterial effect and reduced the treatment duration in neurosurgical patients with post-operative intracranial infections.     

Colistin-based treatment for extensively drug-resistant Acinetobacter baumannii pneumonia

Data for treatment and outcomes of extensively drug-resistant Acinetobacter baumannii (XDR-AB) pneumonia are limited. A retrospective cohort study of 236 adult patients with XDR-AB pneumonia was conducted between January 2009 and December 2012. The median age of subjects was 70 years (range 17–95 years), 53% were male, 55% had ventilator-associated pneumonia and 42% had been admitted to the intensive care unit. All XDR-AB isolates were susceptible only to tigecycline and colistin; 52 (22%) of the 236 subjects did not receive an agent active against XDR-AB, with an associated 28-day survival of 0%. Colistin-based two-drug combination treatment was prescribed to 166 subjects (70%); regimens included (i) colistin and high-dose sulbactam (n = 93); (ii) colistin and tigecycline (n = 43); and (iii) colistin and high-dose prolonged infusion of a carbapenem (n = 30). The 28-day survival rate and mean length of hospital stay were not statistically different between these three regimens (65%, 53% and 60% and 39, 39 and 38 days, respectively). Predictors of mortality included Acute Physiology and Chronic Health Evaluation (APACHE) II score [adjusted odds ratio (aOR) = 1.11; P < 0.001 for each point increase], duration from infection onset to receipt of active regimen (aOR = 1.01; P = 0.002 for each hour delay), underlying malignancy (aOR = 3.46; P = 0.01) and chronic kidney disease (aOR = 2.85; P = 0.03). These findings suggest that the three colistin-based two-drug combination regimens may be treatment options for XDR-AB pneumonia.     

Risk factors for acute kidney injury in patients treated with polymyxin B or colistin methanesulfonate sodium

Polymyxin B (PMB) and colistin, administered as the prodrug colistin methanesulfonate sodium (CMS), are increasingly used to treat carbapenem-resistant Gram-negative bacteria. Nephrotoxicity is the major dose-limiting adverse effect of both polymyxins. A retrospective cohort study of 132 patients was conducted to evaluate risk factors for acute kidney injury (AKI), classified according to Acute Kidney Injury Network criteria, in patients treated with ≥48 h of intravenous PMB or CMS, with particular focus on potential differences between each polymyxin. The overall incidence of AKI was 25.8% (34/132) [20.8% (20/96) and 38.9% (14/36) in patients treated with PMB and CMS, respectively; P = 0.06]. In the Cox regression model, doses ≥2 million International Units (MIU) of PMB or >9 MIU of CMS were the only variable independently associated with AKI [adjusted hazard ratio (aHR) = 2.11, 95% confidence interval (CI) 1.01–4.41; P = 0.04]. Vancomycin co-administration was strongly associated with AKI, although this was not statistically significant (aHR = 2.22, 95% CI 0.98–5.04; P = 0.058). There was no statistically significant difference in the incidence of AKI between patients treated with PMB or CMS in the multivariate model (aHR = 1.74, 95% CI 0.82–3.69; P = 0.15). High dose was the main risk factor for AKI regardless of the polymyxin administered. Vancomycin co-administration likely increases the risk of AKI. Although there was a higher overall incidence of AKI in patients treated with CMS compared with PMB, CMS was not significantly associated with this outcome after adjusting for the above variables.