Inhaled colistin monotherapy for respiratory tract infections in adults without cystic fibrosis: a systematic review and meta-analysis

Background

Inhaled colistin is becoming increasingly popular against respiratory tract infections caused by multidrug resistant (MDR) Gram-negative bacteria because it may overcome the problems associated with intravenous (IV) administration.

Meta-analysis: antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding - an updated Cochrane review

Aliment Pharmacol Ther 2011; 34: 509–518

Summary

Background Antibiotic prophylaxis seems to decrease the incidence of bacterial infections in patients with cirrhosis and upper gastrointestinal bleeding and is considered standard of care. However, there is no updated information regarding the effects of this intervention. Aim To assess the benefits and harms of antibiotic prophylaxis in cirrhotic patients with gastrointestinal bleeding by performing a systematic review of randomised trials. Methods We searched The Cochrane Hepato‐Biliary Group Controlled Trials Register, The Cochrane Central Register of Controlled Trials in The Cochrane Library, MEDLINE, EMBASE and Science Citation Index EXPANDED until June 2010. We statistically combined data calculating relative risk (RR) for dichotomous outcomes and mean difference (MD) for continuous outcomes. Results Twelve trials (1241 patients) evaluating antibiotic prophylaxis against placebo or no antibiotic prophylaxis were included. Antibiotic prophylaxis was associated with reduced mortality (RR 0.79, 95% CI 0.63–0.98), mortality from bacterial infections (RR 0.43, 95% CI 0.19–0.97), bacterial infections (RR 0.35, 95% CI 0.26–0.47), rebleeding (RR 0.53, 95% CI 0.38–0.74) and days of hospitalisation (MD ?1.91, 95% CI ?3.80–0.02). Trials analysing rebleeding rate and hospitalisation length are still scarce, thus, caution should be exerted when interpreting the results. Conclusions Antibiotic prophylaxis in patients with cirrhosis and upper gastrointestinal bleeding significantly reduced bacterial infections, and reduce all‐cause mortality, bacterial infection mortality, rebleeding events and hospitalisation length. Novel clinically significant outcomes were included in this meta‐analysis. Some benefits are biased and the risks are not yet properly assessed, this encourages future research in this field.

     

Differences in the rate of carbapenem-resistant Enterobacteriaceae colonisation or Clostridium difficile infection following frontline treatment with tigecycline vs. meropenem for intra-abdominal infections

Objectives

We hypothesised that treatment with a tigecycline-based antimicrobial regimen for intra–abdominal infection (IAI) could be associated with lower rates of subsequent carbapenem-resistant Enterobacteriaceae (CRE) colonisation or Clostridium difficile infection (CDI) compared with a meropenem-based regimen.

Effect of combination therapy containing a high-dose carbapenem on mortality in patients with carbapenem-resistant Klebsiella pneumoniae bloodstream infection

Objectives

To evaluate the impact of high-dose (HD) carbapenem-based combination therapy on clinical outcome in patients with monomicrobial carbapenem-resistant Klebsiella pneumoniae (CR-KP) bloodstream-infection (BSI).

Meta-analysis of somatostatin, octreotide and gabexate mesilate in the therapy of acute pancreatitis

Background:

Autodigestion of the pancreas, secondary to the activation of digestive enzymes, is the pathogenetic mechanism of acute pancreatitis (AP).

Aim:

Clinical trials in which somatostatin (SS), octreotide (OCT) and gabexate mesilate (FOY) were used to treat patients with AP, were submitted to a meta-analytical evaluation. Five end-points were evaluated: early and overall mortality, patients with complications, complication rate, and patients who needed surgery.

Results:

In mild AP, no agent proved of value. In severe AP, both SS and OCT were beneficial in improving the overall mortality: the odds ratios (OR) were, respectively, 0.36 (95% CI: 0.20–0.64, P = 0.001) and 0.57 (95% CI: 0.35–0.88, P = 0.006). FOY had no effect on either early or overall mortality, but was effective in improving complication rate (OR = 0.70, 95% CI: 0.56–0.88, P = 0.02), number of patients with complications (OR = 0.61, 95% CI: 0.41–0.91, P = 0.01), and number of cases submitted to surgery (OR = 0.60, 95% CI: 0.39–0.92, P = 0.01). SS and OCT had no effect on these latter outcomes.

Conclusions:

Antisecretory agents, such as SS and OCT, are able to reduce mortality without affecting complications, whereas antiproteases, such as FOY, have no effect on mortality but do reduce complications. A trial exploring the efficacy of combining antisecretory agents with antiproteases would be of great benefit in patients with severe AP.

     

Incidence and risk factors of nephrotoxicity in patients on colistimethate sodium

Background Colistin is used to treat gram-negative infections but it’s highly associated with nephrotoxicity. Objectives To determine the incidence and risk factors as well as mortality in patients on colistin. Setting Sultan Qaboos University Hospital, Muscat, Oman. Methods This was a retrospective cohort study of patients admitted and who received colistin for ≥?48 h. The exclusion criteria included inhaled colistin therapy, cystic fibrosis, or pregnancy. The study period was from January 2010 to June 2016. Main outcome measures Nephrotoxicity using the Risk, Injury, Failure, Loss and Endstage kidney disease (RIFLE) criteria. The secondary outcomes were incidence, risk factors and mortality in patients on colistin. Results A total of 123 patients were included. Colistin-associated nephrotoxicity (CAN) occurred in 57 (46%) patients after colistin therapy. As per the RIFLE criteria, 22 (18%) patients were classified as ‘at risk’, 17 (14%) as ‘injury’, and 18 (15%) as ‘failure’. Multivariate analysis indicated that increasing age (adjusted odds ratio (aOR), 1.03; 95% confidence interval (CI) 1.01–1.06; p?=?0.004) and higher APACHE II score (aOR 1.08; 95% CI 1.01–1.16; p?=?0.040) were significant predictors for the development of nephrotoxicity. Factors associated with mortality included ICU admission (aOR 23.3; 95% CI 5.04–106; p?<?0.001), vasopressin use (aOR 5.54; 95% CI 1.56–19.6; p?=?0.008) and higher APACHE II score (aOR 1.15; 95% CI 1.03–1.30; p?=?0.027). Conclusions The incidence of CAN was 46%. Increasing age and higher APACHE II score were the risk factors for CAN. Factors associated with mortality at 28 days included ICU admission and higher APACHE II score.     

Clinical experience with ceftazidime/avibactam for treatment of antibiotic-resistant organisms other than Klebsiella pneumoniae

Background

Ceftazidime/avibactam is a newly approved β-lactam/β-lactamase inhibitor combination with activity against antibiotic-resistant Gram-negative organisms, including many carbapenem-resistant strains. Although this agent may offer a promising treatment option for serious infections with limited alternatives available, clinical experience with ceftazidime/avibactam in treatment of infections caused by multidrug-resistant Gram-negative organisms other than Klebsiella pneumoniae is limited.

Incidence and risk of severe infections associated with aflibercept in cancer patients: a systematic review and meta‐analysis

Aims

Aflibercept is an engineered humanized vascular endothelial growth factor (VEGF)‐targeted agent. Severe infections are serious adverse event associated with aflibercept. However, the contribution of aflibercept to infection is still unknown. We thus conducted this meta‐analysis to investigate the overall incidence and risk of developing severe infections in cancer patients treated with aflibercept.

Methods

Electronic databases including PubMed, Embase and abstracts presented at American Society of Clinical Oncology (ASCO) and European Society of Medical Oncology (ESMO) meeting were searched. Eligible studies were phase II and III prospective clinical trials of aflibercept in cancer patients with toxicity profile on infections. Summary incidences, relative risk (RR), odds ratio (OR) and 95% confidence intervals (95% CIs) were calculated by using either random effects or fixed effect models according to the heterogeneity of included studies.

Results

A total of 4310 patients with a variety of solid tumours from 10 prospective clinical trials were included in the meta‐analysis. The incidence of high grade infections associated with aflibercept was 7.3% (95% CI 4.3, 12.0%), with a mortality of 2.2% (95% CI 1.5, 3.1%). In addition, patients treated with aflibercept had a significantly increased risk of developing high grade (RR 1.87, 95% CI 1.52, 2.30; P < 0.001) and fatal (OR 2.16, 95% CI 1.14, 4.11; P = 0.018) infections. No evidence of publication bias was observed. Furthermore, the risk of infections with aflibercept was substantially higher than bevacizumab.

Conclusions

Aflibercept is associated with a significant increased risk of developing severe infections in patients with solid tumours. Frequent clinical monitoring and appropriate management for infections should be emphasized during aflibercept treatment.     

Meta-analysis: enteral nutrition in active Crohn's disease in children

Summary

Background

Controversy exists surrounding the optimal treatment for inducing remission in active Crohn’s disease.

Aim

To review and update evidence on the effectiveness of enteral nutrition (EN) in treating active Crohn’s disease in children.

Methods

MEDLINE, EMBASE and The Cochrane Library (up to February 2007) were searched for randomized controlled trials (RCTs) relevant to Crohn’s disease and EN in children.

Results

We included 11 RCTs (n = 394). Seven RCTs (n = 204) compared EN with corticosteroid therapy. On the basis of pooled results of four RCTs (n = 144), we found no significant difference in the remission rates between groups (relative risk, RR 0.97, 95% CI 0.7–1.4, random effect model). Four RCTs (n = 190) compared two EN regimens. One of the four RCTs (n = 50) revealed a significant increase in the percentage of patients achieving remission in the total EN group compared with the partial EN group (RR 2.7, 95% CI 1–7.4). Because of lack of data, formal pooling of results was not possible for many outcomes (e.g., time until remission, duration of remission, growth data).

Conclusions

Limited data suggest similar efficacy for EN and corticosteroids. As the number of patients needed to provide a definite answer is too large, future studies should focus on detailed outcome measurements including growth and quality of life.

     

The prevalence of benzodiazepines utilization and its association with falls among Saudi older adults; results from the Saudi national survey for elderly Health (SNSEH)

Purpose

First, to determine benzodiazepines prevalence (BDZs) among Saudi older adults (SOA); Second, to quantify the association between BDZs use and falls among SOA. Third, to determine falls effect on all-cause mortality among SOA.

Empiric antibiotic protocols for cancer patients with neutropenia: a single–center study of treatment efficacy and mortality in patients with bacteremia

Background

There are several empiric antibiotic treatment options for febrile neutropenia, yet there is no universally-accepted initial protocol. We aimed to assess the performance of a protocol (piperacillin, gentamicin and cefazolin) introduced over 40 years ago and compare its coverage against bacteria isolated from blood of neutropenic patients with that of various commonly used antibiotic treatment protocols.

Moxifloxacin plus rifampin as an alternative for levofloxacin plus rifampin in the treatment of a prosthetic joint infection with Staphylococcus aureus

Objectives

The combination of a fluoroquinolone with rifampin is one of the cornerstones in the treatment of prosthetic joint infections (PJI) caused by staphylococci. Moxifloxacin is highly active against methicillin–susceptible Staphylococcus aureus (MSSA) and, therefore, is an attractive agent to use. However, several studies reported a lowering in serum moxifloxacin levels when combined with rifampin. The clinical relevance remains unclear. We determined the outcome of patients with early acute PJI caused by MSSA treated with either moxifloxacin/rifampin or levofloxacin/rifampin.

Omeprazole 20 or 40 mg daily for healing gastroduodenal ulcers in patients receiving non-steroidal anti-inflammatory drugs

Background

Non-steroidal anti-inflammatory drugs (NSAIDs) are strongly associated with gastroduodenal ulcers, and the management of patients with NSAID-associated ulcers represents a common clinical dilemma.

Aim

To assess NSAID-associated ulcer healing during treatment with either standard (20 mg) or high dosage (40 mg) omeprazole.

Methods

One hundred and sixty-nine patients chronically ingesting diclofenac, ketoprofen, indome-thacin or naproxen for osteoarthritis or rheumatoid arthritis, who had abdominal pain and an endoscopically proven gastroduodenal ulcer, were evaluated in a randomized, double-blind, dose regimen trial with omeprazole 20 mg o.m. (n = 81) or omeprazole 40 mg o.m. (n = 88). Ulcer healing was assessed endoscopically at 4 and 8 weeks in the case of unhealed ulcers. Patients continued their usual daily dose of anti-inflammatory medication throughout the study period.

Results

One hundred and fifty-six patients completed the study (77 patients taking 20 mg omeprazole and 79 patients taking 40 mg omeprazole); 12 patients were lost during follow-up and one patient reported an adverse event. Cumulative ulcer intention-to-treat healing rates at 8 weeks were 88% (95% confidence interval (CI) = 79–95%) for the 20 mg omeprazole group and 96.2% (95% CI = 89–99%) for the 40 mg group, and 97.1% (95% CI = 90–100%) for the 20 mg omeprazole group and 98.6% (95% CI = 93–100%) for the 40 mg group by per protocol analysis. There were no statistically significant differences between the two groups. Symptom relief did not differ significantly between the two treatment groups.

Conclusion

Both standard and high doses of omeprazole are equally safe and effective regimens for the treatment of NSAID-induced gastroduodenal ulcers when anti-inflammatory treatment is not discontinued.

     

Variation in taste of topical lignocaine anaesthesia for gastroscopy

Aim:

To study the distribution and determinants of taste variation for lignocaine spray (Xylocaine; Astra Pharmaceuticals, King’s Langley, UK).

Methods:

Sixty-nine patients (male:female 49:20, mean age 48.5 years) attending for open access upper gastrointestinal endoscopy were studied. Taste perceived after applying 4 doses (40 mg) of lignocaine spray to the oro-pharynx was recorded prior to endoscopy.

Results:

37/69 (54%, 95% CI: 41–66%) perceived the taste of the lignocaine spray as bitter, whilst 24/69 (35%, 95% CI: 24–47%) and 6/69 (9%, 95% CI: 3–18%) perceived the taste as either fruity/sweet or tasteless. The variation in taste did not correlate with either demographic features or H. pylori infection, but duodenal ulceration was slightly more common amongst bitter tasters.

Conclusion:

The taste of lignocaine is not uniform, but the basis of this variability is uncertain.

     

Randomized controlled trial of omeprazole or endoscopy in patients with persistent dyspepsia: a cost-effectiveness analysis

Background

Cost-effectiveness analysis, Helicobacter pylori research and the development of proton pump inhibitors are having an increasing impact on the management of dyspepsia. However, clinical trials have not always included both H. pylori diagnosis and proton pump inhibitors in their protocols.

Methods

Patients who were referred for upper gastrointestinal endoscopy by their general practitioner were randomized to either prompt endoscopy followed by directed medical treatment (conventional group, n = 38), or to empirical treatment with omeprazole and, in the case of symptom relapse, serological screening for H. pylori infection followed by eradication therapy in seropositive patients (empirical group, n = 42). The study lasted for up to 1 year.

Results

In the empirical group, only 13 patients (31%) underwent endoscopy. The average number of days for which the patients kept records of their dyspeptic symptoms was 266 (95% CI: 226–307) in the empirical group, of which 166 (95% CI: 128–204) were symptom-free. In the conventional group, 159 (95% CI: 119–198) out of 255 days (95% CI: 209–302) were recorded as symptom-free. The average medical cost in the empirical group was 284 (95% CI: 218–350) and in the conventional group 491 (95% CI: 383–600). In the empirical group, two malignancies were found, whereas in the conventional group one malignancy was found.

Conclusions

The empirical drug treatment strategy in patients with persistent dyspeptic symptoms resulted in 69% fewer diagnostic endoscopies with lower medical costs and equal effectiveness in the first year, compared to prompt endoscopy followed by directed medical treatment.

     

Prostanoid therapy for pulmonary arterial hypertension: a meta-analysis of survival outcomes

Background

Prostanoids have played an important role in the treatment of pulmonary arterial hypertension (PAH). However, whether prostanoid therapy provides a survival advantage is still not clear. The aim of this meta-analysis was to evaluate the efficacy and safety of prostanoids in PAH, focusing on the improvement in overall survival.

Methods

Trials were identified from the Cochrane Library, EMBASE, and PUBMED databases. We calculated risk ratios (RR) for dichotomous data and weighted mean differences with 95 % confidence intervals (CI) for continuous data.

Results

Fourteen trials with a total of 2,244 adult patients (1,189 patients in the prostanoid treatment group and 1,055 patients in the placebo group) were included in the meta-analysis. All-cause mortality rate in the control group was 4.17 %. In a 13.4-week follow-up, prostanoid treatment was associated with a 44 % reduction in mortality (RR 0.56; 95 % CI 0.35–0.88; P = 0.01).Subgroup analysis suggested that only treatment with intravenous prostanoids provided a survival benefit. Compared with placebo, prostanoids significantly reduced clinical worsening (RR 0.60; 95 % CI 0.46–0.80; P = 0.0003), increased the 6-min walk distance by 27.95 m, reduced mean pulmonary arterial pressure and pulmonary vascular resistance, and increased the cardiac index and mixed venous oxygen saturation. However, patients receiving prostanoid treatment showed a much higher incidence (RR 3.25; 95 % CI 2.07–5.10; P?<?0.00001) of withdrawal due to its adverse effects.

Conclusion

The results of this meta-analysis suggest that treatment with prostanoids improves the survival of patients with PAH.     

Two-day 'weekend' lansoprazole-quadruple therapy for Helicobacter pylori infection

Background:

The very high cure rate of 1-week quadruple therapy offers an opportunity to study a shorter treatment duration. This is needed to construct a time–response curve for the regimen.

Methods:

Fifty-two patients with endoscopically proven H. pylori infection received lansoprazole 30 mg b.d., tripotassium dicitrato bismuthate 120 mg q.d.s., tetracycline 500 mg q.d.s. and metronidazole 500 mg q.d.s., following 3 days of lansoprazole pre-treatment. A second endoscopy was performed at least 6 weeks later. A patient was cured if histology, CLO-test, and culture of antrum and corpus were negative.

Results:

We achieved an intention-to-treat cure rate of 30/50 (60%, 95% CI: 46–73%) and a per protocol cure rate of 30/48 (63%, 95% CI: 48–75%). Cure rate in metronidazole-sensitive strains was 24/37 (65%, 95% CI: 48–79%) and 2/5 (40%) in resistant strains. All patients that failed the regimen had a metronidazole-resistant strain post-treatment. Compliance was excellent and moderate or severe side-effects occurred in only 4% of patients.

Conclusion:

A 2-day ‘weekend’ quadruple therapy cures only 60% of patients and cannot be recommended, but these findings provide an insight into the mode of action of quadruple therapy.

     

High Helicobacter pylori eradication rate with a 1-week regimen containing ranitidine bismuth citrate

Background:

High Helicobacter pylori eradication rates have consistently been reported with 2-week dual therapy regimens of ranitidine bismuth citrate plus clarithromycin. Ranitidine bismuth citrate with two antibiotics may provide an alternative 1-week eradication regimen.

Methods:

This double-blind, randomized, parallel group, international, multicentre study compared ranitidine bismuth citrate 400 mg b.d. and clarithromycin 500 mg b.d. for 2 weeks (RC) with ranitidine bismuth citrate 400 mg b.d., clarithromycin 500 mg b.d. and metronidazole 400 mg b.d. for 1 week (RCM) for eradication of H. pylori in 350 patients with dyspepsia.

Results:

Treatment with RC and RCM eradicated H. pylori (established by the combination of two negative results from two discrete ¹³C-UBTs at nominal weeks 4 and 12) from 89% (95% CI: 84–94) and 92% (95% CI: 88–97) of the observed population, and from 78% (95% CI: 72–84) and 80% (95% CI: 75–86) of the intention-to-treat population. When established only by one negative ¹³C-UBT result at least 28 days after the end of treatment, the respective intention-to-treat rates were 85% (95% CI; 79–90) and 88% (95% CI: 83–93). Both regimens were well-tolerated, only 6% of patients given RC and 4% given RCM discontinued treatment. Median plasma bismuth concentrations at the end of the second week of study were low, at 3.5 and 0.4 ng/mL, respectively.

Conclusions:

Ranitidine bismuth citrate triple therapy for 1 week (RCM) and dual therapy for 2 weeks (RC) were equally effective for the eradication of H. pylori infection.

     

Incidence and relative risk of grade 3 and 4 diarrhoea in patients treated with capecitabine or 5- fluorouracil: a meta-analysis of published trials

Aim

Capecitabine is an oral fluoropyrimidine that can effectively replace infusional 5-fluorouracil (5-FU) for treatment of colorectal, gastric and breast cancer. This study aims to analyze the incidence and the relative risk of grade 3 and 4 diarrhoea in patients treated with capecitabine or 5-FU in randomized clinical trials (RCTs).

Methods

MEDLINE and Cochrane Library were reviewed for RCTs that compared capecitabine with 5-FU for treatment of solid malignancies. The incidence and relative risk (RR) of grade 3/4 diarrhoea were estimated for each arm in the overall population and in colorectal cancer (CRC) patients

Results

Twenty-three studies and 15 761 patients were included. Among these 8303 and 7458 patients received capecitabine or 5-FU based therapies, respectively. In the overall populations severe diarrhoea was reported in 16.6% (95% CI 15.8, 17.4) and in 12.7% (95% CI 11.9, 13.4) of patients treated with capecitabine or 5-FU-based therapies, respectively. The RR was 1.39 (95% CI 1.14, 1.69, P = 0.0010). In 14 899 CRC patients, the incidence of severe diarrhoea was 17.0% (95% CI 16.2, 17.9) and 12.9% (95% CI 12.1, 13.7), respectively, with a RR of 1.46 (95% CI 1.18, 1.81, P < 0.0001). In CRC patients treated with combined chemotherapy, the RR was 1.40 (95% CI 1.07, 1.82; P = 0.01) for patients receiving oxaliplatin and 2.35 (95% CI 1.76, 3.13; P < 0.0001) for patients receiving irinotecan.

Conclusions

Treatment with capecitabine is characterized by an increased risk of severe diarrhoea, mainly in patients affected by CRC and treated with polichemotherapy. Combination treatment with irinotecan doubles the risk over 5-FU.     

Bevacizumab increases the risk of gastrointestinal perforation in cancer patients: a meta-analysis with a focus on different subgroups

Background

The aim of this meta-analysis was to gather current data and evaluate not only the risk of gastrointestinal (GI) perforation with bevacizumab, but also the potential risk factors for this adverse event.

Materials and methods

We carried out a literature search in PubMed for randomized controlled trials (RCTs) reported from January 2000 to December 2013. Summary incidence, relative risks (RRs) and 95 % confidence intervals (CIs) were calculated using random-effects or fixed-effects models based on the heterogeneity of the included studies.

Results

A total of 26,833 patients from 33 RCTs were included in the meta-analysis. Bevacizumab-containing therapy significantly increased the risk of developing all-grade (RR 3.35, 95 % CI 2.35–4.79, P?<?0.001) and fatal GI perforation (RR 3.08, 95%CI: 1.04–9.08, P?=?0.042). On subgroup analysis, no significant risk differences were found based on bevacizumab dosage, treatment duration, treatment line, type of clinical trial and median age. When stratified by tumor types, a significantly increased risk of GI perforation with bevacizumab was observed in colorectal cancer (RR 2.84, 95% CI 1.43–5.61, P?=?0.003), gynecologic cancer (RR 3.37, 95% CI 1.71–6.62, P?<?0.001) and prostate cancer (RR 6.01, 95% CI 1.78–20.28, P?=?0.004). Additionally, the use of bevacizumab significantly increased the risk of GI perforation when used in conjunction with taxanes (RR 3.09, 95% CI 1.92–4.96, P?<?0.001) or oxaliplatin (RR 2.85, 95% CI 1.07–7.57, P?=?0.036).

Conclusions

Bevacizumab treatment is associated with a significantly increased risk of developing GI perforation, and clinicians should be aware of the risks of GI perforation with the administration of this drug in cancer patients.