Treatment Failure Due to Adaptive Resistance Mechanisms in a Severe and Complicated Bloodstream Infection Due to Elizabethkingia meningoseptica.

Elizabethkingia meningoseptica is an uncommonly encountered multidrug-resistant gram-negative bacterium that causes infections primarily among vulnerable hosts. A true opportunistic pathogen, its ability to cause severe sepsis and complicated infection in selected patients has been noted. Very limited preclinical and clinical data exist with regard to suitable therapeutic options. In this study, we present the case of prolonged bloodstream and central nervous system infection due to E. meningoseptica treated with dose-optimized combination antibiotic therapy, with evidence of microbiological (including development of adaptive resistance mechanisms) and clinical failure.

Efficacy and Safety of Carbapenems vs New Antibiotics for Treatment of Adult Patients With Complicated Urinary Tract Infections: A Systematic Review and Meta-analysis.

This systematic review and meta-analysis evaluated the clinical efficacy and safety of carbapenems for the treatment of complicated urinary tract infections (cUTIs), with the comparators being new antibiotics evaluated for this indication. We searched 13 electronic databases for published randomized controlled trials (RCTs) and completed and/or ongoing trials. The search terms were developed using the Population, Intervention, Comparison, Outcomes, and Study framework. Pooled efficacy estimates of composite cure (clinical success and microbiological eradication) favored the new antibiotic groups, although this was not statistically significant (risk ratio [RR], 0.91; 95% CI, 0.79-1.04). A pooled estimate examining clinical response alone showed no difference between treatment arms (RR, 1.00; 95% CI, 0.96-1.05), however, new antibiotic treatments were superior to carbapenems for microbiological response (RR, 0.85; 95% CI, 0.79-0.91). New antibiotic treatments demonstrated a superior microbiological response compared with carbapenems in clinical trials of cUTI, despite an absence of carbapenem resistance. However, it is noteworthy that the clinical response and safety profile of new antibiotics were not different from those of carbapenems.

Investigator-Driven Randomised Controlled Trial of Cefiderocol versus Standard Therapy for Healthcare-Associated and Hospital-Acquired Gram-negative Bloodstream Infection: Study protocol (the GAME CHANGER trial): study protocol for an open-label, randomised controlled trial.

BACKGROUND: Increasing rates of antibiotic resistance in Gram-negative organisms due to the presence of extended-spectrum beta-lactamases (ESBL), hyperproduction of AmpC enzymes, carbapenemases and other mechanisms of resistance are identified in common hospital- and healthcare-associated pathogens including Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter baumannii. Cefiderocol is a novel siderophore cephalosporin antibiotic with a catechol moiety on the 3-position side chain. Cefiderocol has been shown to be potent in vitro against a broad range of Gram-negative organisms, including carbapenem-resistant Enterobacteriaceae (CRE) and multi-drug-resistant (MDR) P. aeruginosa and A. baumannii. Recent clinical data has shown cefiderocol to be effective in the setting of complicated urinary tract infections and nosocomial pneumonia, but it has not yet been studied as treatment of bloodstream infection. METHODS: This study will use a multicentre, open-label non-inferiority trial design comparing cefiderocol and standard of care antibiotics. Eligible participants will be adult inpatients who are diagnosed with a bloodstream infection with a Gram-negative organism on the basis of a positive blood culture result where the acquisition meets the definition for healthcare-associated or hospital-acquired. It will compare cefiderocol with the current standard of care (SOC) antibiotic regimen according to the patient's treating clinician. Eligible participants will be randomised 1:1 to cefiderocol or SOC and receive 5-14 days of antibiotic therapy. Trial recruitment will occur in at least 20 sites in ten countries (Australia, Malaysia, Singapore, Thailand, Turkey and Greece). The sample size has been derived from an estimated 14 day, all-cause mortality rate of 10% in the control group, and a non-inferiority margin of 10% difference in the two groups. A minimum of 284 patients are required in total to achieve 80% power with a two-sided alpha level of 0.05. Data describing demographic information, risk factors, concomitant antibiotics, illness scores, microbiology, multidrug-resistant organism screening, discharge and mortality will be collected. DISCUSSION: With increasing antimicrobial resistance, there is a need for the development of new antibiotics with broad activity against Gram-negative pathogens such as cefiderocol. By selecting a population at risk for multi-drug-resistant pathogens and commencing study treatment early in the clinical illness (within 48 h of index blood culture) the trial hopes to provide guidance to clinicians of the efficacy of this novel agent. TRIAL REGISTRATION: The GAME CHANGER trial is registered under the US National Institute of Health ClinicalTrials.gov register, reference number NCT03869437 . Registered on March 11, 2019.

Hydatid disease, hepatic injury and hypertonic saline: a clinical conundrum.

Echinococcosis or human hydatid disease is a helminthic infection is caused by Echinococcus species. Classically, cystic echinococcosis is caused by Echinococcus granulosus sensu stricto, E. equinus, E. ortleppi and E. canadensis, though several other species have been implicated in hydatid disease. Echinococcus infection may lead to cystic disease of the liver, lungs and potentially other organs. Here we present a patient who had cystic disease of the lungs and liver. The patient initially experienced right upper quadrant pain and nausea, and later went on to develop a fever, cough and dyspnoea in the setting of hydropneumothorax. CT scan of the chest and abdomen revealed a large fluid collection at the left lung base and a large lobular complex fluid mass within the right lobe of the liver. Echinococcus titres were positive. The patient was commenced on albendazole; however, experienced significant derangement of liver enzymes within the following month. In light of this, the albendazole was ceased, and a hemi-hepatectomy was performed. During the hemi-hepatectomy there was some cyst content spillage, and subsequently a washout with hypertonic saline 3% was performed. This was followed by a course of praziquantel 1200 mg two times per day for 14 days. Repeat CT 6 months later demonstrated no evidence of recurrence.

Meropenem-induced liver injury and beta-lactam cross-reactivity.

A 63-year-old man admitted to hospital for the management of a frontal lobe abscess developed elevated liver enzymes within 48 hours of receiving meropenem. Liver enzymes reached a maximum at 5 days postadministration of meropenem, with alanine aminotransferase 1160 U/L, aspartate aminotransferase 787 U/L, alkaline phosphatase 297 U/L and gamma-glutamyltransferase 252 U/L. Meropenem was ceased and liver function normalised. Meropenem was administered for a second time later in the patient's admission and again the patient developed rapidly increasing liver enzymes, with a mixed hepatocellular/cholestatic pattern. Other possible causes of liver injury were excluded following extensive investigations, and the patient's liver enzymes continued to normalise following meropenem discontinuation. The patient was asymptomatic during the admission and was transferred to a rehabilitation facility. This case demonstrates that meropenem can cause severe liver injury and that early recognition of drug-induced liver injury is important.

Long-term morbidity and mortality following bloodstream infection: A systematic literature review.

OBJECTIVES: Bloodstream infection results in significant short-term morbidity and mortality. No literature review has studied the long-term outcome following a bloodstream infection. This PROSPERO registered systematic review evaluated studies, which measured the association of a bloodstream infection with long-term morbidity and mortality. METHODS: Databases were systematically searched for studies of adult patients reporting morbidity and/or mortality one year or more following a bloodstream infection in comparison to a matched cohort without a bloodstream infection. RESULTS: Ten observational studies were included in the final analysis. Five studies assessed only mortality, two assessed morbidity and mortality and three studies assessed morbidity only. The one year mortality ranged from between 8 and 48% for patients with bloodstream infection. The pooled risk ratio of death at one year was significantly higher for patients with bloodstream infection when compared to the matched cohort (RR 4.04 [95% CI 1.84-8.87]). CONCLUSIONS: Bloodstream infection was associated with poor long-term outcome measured at one year when compared to matched controls. More evidence is needed to determine if this association is causative.

Health Risks of Flood Disasters.

Floods are the most common natural disaster occurring worldwide, with their impact expected to grow in the future due to the effects of climate change and population shift. Floodwaters pose immediate dangers to human health, but also long-term effects resulting from displacement and worsened living conditions. This review examines the health impact of flood disasters, including skin and soft-tissue infections, gastroenteritis, and zoonotic infections such as leptospirosis, and the impact on noncommunicable diseases and health infrastructure. Further work in the development of cost-efficient preparedness strategies may mitigate the morbidity and mortality associated with such natural disasters.

Consideration for eliminating conjunctival closure in the enucleation procedure.

To compare post-operative results and complications in patients who undergo enucleation with or without suture closure of the conjunctiva. This was a retrospective chart review study. Review of 50 cases of enucleation surgery at the University of Arkansas for Medical Sciences and Arkansas Children's Hospital between July 2011 and December 2014. Criteria for inclusion in the study were all cases of enucleation that had extraocular muscles attached to a spherical orbital implant with or without conjunctival closure, and at least 2 months of postoperative follow up. Post-operative complications were evaluated. A total of 36 cases fulfilled the criteria for inclusion in the study; 12 cases with direct sutured layered direct closure of Tenon's and then conjunctiva and 24 cases with Tenon's capsule sutured closure but without direct conjunctival sutured closure. No implant complications were identified in either group (p = 1.0). Mean follow-up for all groups was 16.71 months (range 2 to 43 mo., SD 11.94). Mean follow up for the non-closure group was 14.42 months (range 2.25 to 36 mo., SD 10.35). Two cases in the conjunctival closure group developed a conjunctival cyst, affecting prosthesis fit, approximately 3 months postoperatively: no such cysts were identified in the non-conjunctival closure group. Fisher exact test for cyst formation between the two groups was not statistically significant (p = 0.1048). Direct conjunctival closure following enucleation surgery does not appear to increase the risk of extrusion, exposure, or infection. Foregoing direct closure decreases surgical time and reduces cost. It is unclear if this decreases conjunctival cyst formation.

Diplopia is better than no plopia!

Idiopathic intracranial hypertension often presents with cranial nerve VI paresis. Infrequently, other cranial nerve dysfunction may occur. We report a case of idiopathic intracranial hypertension that presented with bilateral cranial nerve III paresis. Review of the literature suggests that severe elevation of intracranial pressure may predispose patients with idiopathic intracranial hypertension to cranial nerve III dysfunction.

What works in conservation? Using expert assessment of summarised evidence to identify practices that enhance natural pest control in agriculture.

This paper documents an exercise to synthesize and assess the best available scientific knowledge on the effectiveness of different farm practices at enhancing natural pest regulation in agriculture. It demonstrates a novel combination of three approaches to evidence synthesis-systematic literature search, collated synopsis and evidence assessment using an expert panel. These approaches follow a logical sequence moving from a large volume of disparate evidence to a simple, easily understandable answer for use in policy or practice. The example of natural pest regulation in agriculture was selected as a case study within two independent science-policy interface projects, one European and one British. A third funder, a private business, supported the final stage to translate the synthesized findings into a useful, simplified output for agronomists. As a whole, the case study showcases how a network of scientific knowledge holders and knowledge users can work together to improve the use of science in policy and practice. The process identified five practices with good evidence of a benefit to natural pest regulation, with the most beneficial being 'Combine trap and repellent crops in a push-pull system'. It highlights knowledge gaps, or potential research priorities, by showing practices considered important by stakeholders for which there is not enough evidence to make an assessment of effects on natural pest regulation, including 'Alter the timing of pesticide application.' Finally, the process identifies several important practices where the volume of evidence of effects on natural pest regulation was too large (>300 experimental studies) to be summarised with the resources available, and for which focused systematic reviews may be the best approach. These very well studied practices include 'Reduce tillage' and 'Plant more than one crop per field'.

Rapidly growing mycobacteria associated with laparoscopic gastric banding, Australia, 2005-2011.

Laparoscopic gastric banding is a common bariatric procedure worldwide. Rapidly growing mycobacteria are environmental organisms increasingly seen as pathogens,often in infected prosthetic material. We report 18 cases of infection associated with laparoscopic gastric banding caused by Mycobacterium fortuitum and M. abscessus in Australia during 2005­2011. We identified cases by reviewing positive cultures at the Queensland state reference laboratory or through correspondence with clinicians, and we obtained clinical and epidemiologic data. Eleven cases of M. fortuitum and 7 cases of M. abscessus infection were identified. The port was thought to be the primary site of infection in 10 of these cases. Complications included peritonitis,band erosion, and chronic ulceration at the port site.Rapidly growing mycobacteria can infect both port and band and can occur as either an early perioperative or late infection.Combination antimicrobial therapy is used on the basis of in vitro susceptibilities. Device removal seems to be vital to successful therapy.