Multidrug-resistant Pneumonia Research Articles

Reducing Multidrug-Resistant (MDR) Klebsiella pneumoniae via the Efficient Use of Bacteriophages ZI3 and HI3

Klebsiella pneumoniae is a common cause of multidrug-resistant (MDR) pneumonia, bacteremia, urinary tract infections (UTIs), and other systemic infections. K. pneumoniae is the third most common pathogen in blood cultures from sepsis patients. It can cause severe epidemic and endemic nosocomial infections. Antibiotic treatment of K. pneumoniae infections is getting increasingly challenging due to the development of antimicrobial resistance among pathogens. Hence, a new alternative strategy is required to treat such infections. Bacteriophages are the most prevalent biological entity on the planet with an estimated 1031 particles. As obligatory intracellular parasites, they infect bacterial cells. They have a high host specificity and can replicate and lyse bacterial cells. In this research, two novel indigenous bacteriophages against K. pneumoniae strain kp8890 were isolated, characterized, and labeled as ZI3 and HI3. Both these phages were found to have a specific host range for K. pneumoniae. HI3 was able to lyse 7 out of 10 different K. pneumoniae clinical isolates, while ZI3 was able to lyse 5 out of 10 isolates, although it could not infect bacteria from other species. The isolated phages showed viability up to 50°C and pH ranging from 3 to 9. HI3 inhibited bacterial growth for 18 hours. Whereas, ZI3 showed an excellent bacterial reduction ability by inhibiting and decreasing the number of initial bacterial inoculum for 24 hours of observation. Keeping in view the excellent bacterial growth reduction, phage titer, pH and thermal stability, and host range, it is suggested that both bacteriophages, that is, ZI3 and HI3 can be potential phage therapy candidates after necessary animal modeling and clinical trials in the future.

Distribution of bacteria and risk factors in patients with multidrug-resistant pneumonia in a single center rehabilitation ward.

Stroke patients may have dysphagia and frequent aspiration increasing exposure to antibiotics and the chance of multidrug-resistant (MDR) bacteria infection. This study investigated clinical risk factors and related antibiotic use of MDR bacteria infection in stroke patients in the rehabilitation ward, hoping that it can help prevent and reduce the condition of MDR bacteria. A retrospective cohort study was conducted using the database of stroke patients with pneumonia admitted to the rehabilitation ward from January 1, 2020, to June 30, 2022. The selected stroke patients were divided into the MDR and non-MDR groups. Analyze the infection bacteria of the 2 groups. Forward logistic regression was applied to identify possible independent MDR bacteria infection risk factors. A total of 323 patients were included. The top 3 common MDR pathogens were Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii. Almost all Pseudomonas aeruginosa and Acinetobacter baumannii are resistant to ertapenem. National Institute of Health stroke scale at admission was associated with MDR bacteria infection pneumonia (OR [odds ratio] = 1.078, 95%CI [1.017, 1.142]). Long-term tracheotomy (OR = 2.695, 95%CI [1.232, 5.897]), hypoalbuminemia (OR = 473, 95%CI [1.318, 4.642]), and bilateral cerebral hemisphere stroke (OR = 4.021, 95%CI [2.009, 8.048]) were significant clinical risk factors of MDR pneumonia after stroke. The detection rate of MDR bacteria has increased. Understanding the distribution and drug resistance of MDR bacteria in stroke patients with pneumonia in the neurological rehabilitation ward and the related susceptibility of MDR bacteria infection is necessary. This way, the treatment plan can be adjusted more timely, avoiding the abuse of antibiotics.

The relationship between renal functions and multi-drug resistant organisms in patients with ventilator-associated pneumonia

Objective: Despite the increase in the frequency of multi-drug resistant organism (MDRO) colonisation and infection in dialysis
 patients, it is not well known whether the risk of multi-drug resistant (MDR) pneumonia increases in mild-to-severe chronic kidney
 disease patients not undergoing dialysis. Therefore, we aimed to evaluate the relationship between renal functions and the risk of MDR
 ventilator-associated pneumonia (VAP) and the specific microbial pattern.
 Patients and Methods: A total of 133 patients who developed VAP were divided according to their renal function into two groups, an
 estimated glomerular filtration rate of (eGFR) ≥ 60 mL/ min/1.73 m2 (high eGFR, n=65) and eGFR < 60 mL/min/1.73 m2 (low eGFR,
 n=68).
 Results: The low eGFR group presented a significantly high MDRO ratio (p

Treatment of infection and inflammation associated with COVID-19, multi-drug resistant pneumonia and fungal sinusitis by nebulizing a nanosilver solution

Solutions containing Ag0 nanoclusters, Ag+1, and higher oxidation state silver, generated from nanocrystalline silver dressings, were anti-inflammatory against porcine skin inflammation. The dressings have clinically-demonstrated broad-spectrum antimicrobial activity, suggesting application of nanosilver solutions in treating pulmonary infection.Nanosilver solutions were tested for antimicrobial efficacy; against HSV-1 and SARS-CoV-2; and nebulized in rats with acute pneumonia. Patients with pneumonia (ventilated), fungal sinusitis, burns plus COVID-19, and two non-hospitalized patients with COVID-19 received nebulized nanosilver solution.Nanosilver solutions demonstrated pH-dependent antimicrobial efficacy; reduced infection and inflammation without evidence of lung toxicity in the rat model; and inactivated HSV-1 and SARS-CoV-2. Pneumonia patients had rapidly reduced pulmonary symptoms, recovering pre-illness respiratory function. Fungal sinusitis-related inflammation decreased immediately with infection clearance within 21 days. Non-hospitalized patients with COVID-19 experienced rapid symptom remission.Nanosilver solutions, due to anti-inflammatory, antiviral, and antimicrobial activity, may be effective for treating respiratory inflammation and infections caused by viruses and/or microbes.

Development of Host Immune Response to Bacteriophage in a Lung Transplant Recipient on Adjunctive Phage Therapy for a Multidrug-Resistant Pneumonia.

Bacteriophage therapy is the use of viruses to kill bacteria for the treatment of antibiotic-resistant infections. Little is known about the human immune response following phage therapy. We report the development of phage-specific CD4 T cells alongside rising phage-specific immunoglobulin G and neutralizing antibodies in response to adjunctive bacteriophage therapy used to treat a multidrug-resistant Pseudomonas aeruginosa pneumonia in a lung transplant recipient. Clinically, treatment was considered a success despite the development phage-specific immune responses.

Incidence and Impact of Ventilator Associated Multidrug Resistant Pneumonia in Patients with SARS-COV2.

Introduction Ventilator Associated Pneumonia (VAP) is associated with significant cost, morbidity, and mortality. There is limited data on the incidence of VAP, appropriate antibiotic timing, and the impact of multidrug resistant VAP in intubated Coronavirus disease-19 (COVID-19) patients. Methods A retrospective study was conducted at 2 tertiary urban academic centers involving 132 COVID-19 patients requiring invasive mechanical ventilation (IMV). The epidemiology of VAP, the impact of prior empiric antibiotic administration on the development of Multidrug Resistant Organism (MDRO) infections, and the impact of VAP on patient outcomes were studied. Results The average age of the patients was 60.58% were males, 70% were African-Americans and two-thirds of patients had diabetes, hypertension, or heart disease. The average Body Mass Index (BMI) was 32.9. Forty-one patients (27%) developed VAP. Patients with VAP had a significantly higher Sequential Organ Failure Assessment (SOFA) score prior to Intensive Care Unit (ICU) admission. Sixty percent received empiric antibiotics before initiation of IMV, mostly on hospital admission, and 81% received empiric antibiotics at the time of intubation. The administration of empiric antibiotics was not associated with a higher prevalence of VAP. The prevalence of VAP was 22 per 1000 days on ventilation. No difference in mortality was seen between VAP and non-VAP groups at 49% and 57% respectively (p = 0.4). VAP was associated with increased ICU length of stay (LOS), 30 vs. 16 days (p < 0.001), and longer hospital LOS 35 vs. 17 days (p < 0.001). 40% of VAPs were caused by MDROs. The most common organism was Staphylococcus aureus (28%), with almost half (48%) being methicillin resistant Staphylococcus aureus (MRSA). Conclusion VAP was a common complication of patients intubated for COVID-19 pneumonia. Most patients received empiric antibiotics upon the hospital and/or ICU admission. There was a 40% incidence of multidrug resistant pneumonia. Patients who developed VAP had almost twice as long hospital and ICU LOS.

Archimedes® Absorbable Internal Biliary Stent in Liver Transplants to Prevent Bile Leak

Introduction: Biliary complications, especially bile leaks are an important cause of early post-operative morbidity and rarely mortality after liver transplant. The risk is higher in living donor liver transplant (LDLT) compared to deceased donor liver transplant (DDLT) because of many well-known factors. Attempts to reduce bile leaks have included improvements in graft retrieval, refinements in the biliary anastomosis technique and use of various external and internal stents with inconsistent benefits. Recent availability and successful use of the absorbable Archimedes® stent has prompted its intra-biliary placement across the anastomosis. Methods: In this retrospective study, we analyzed data of 20 adult patients who underwent liver transplantion from December 2019 to January 2020 with duct-to-duct biliary anastomosis (DDA) using Archimedes® stent.. Liver Transplantion was performed using cava-preserving hepatectomy followed by standard implantation methods. Duct-to-duct (DDA) biliary anastomosis was performed using interrupted polydioxanone sutures with extracorporeal knots over an absorbable intra-biliary stent. Results: Nine DDLT had a single anastomosis over a 10Fr stent. Out of 11 LDLT patients, 7 had a single anastomosis and 4 patients had two anastomosis, all over a 6Fr stent. Two patients died due to graft primary non-function and multi-drug resistant pneumonia respectively. One patient had ascending cholangitis due to stent migration and was managed with endoscopic stent removal and appropriate antibiotics. None of the other patients had bile leak, bilioma, stent related complications or required any endoscopic or radiological procedure. Conclusions: Archimedes® internal absorbable biliary stents can be safely used in both LDLT and DDLT to prevent bile leaks.

Treatment of Infection and Inflammation Associated with COVID-19, Multi-Drug Resistant Pneumonia and Fungal Sinusitis by Nebulizing a Nanosilver Solution

Treatment of Infection and Inflammation Associated with COVID-19, Multi-Drug Resistant Pneumonia and Fungal Sinusitis by Nebulizing a Nanosilver Solution

Clinical Implication of Candida Score in Multidrug-Resistant Pneumonia with Airway Candida Colonization.

BackgroundThe growth of Candida in respiratory secretions is usually considered colonization, and antifungal therapy is rarely required. The role of Candida colonization in the progression of bacterial pneumonia remains controversial. The aim of this study was to identify the clinical implication of Candida score by analyzinge the relationship with multidrug-resistant (MDR) pneumonia and prognosis in patients with airway Candida colonization.Materials and MethodsThis study was a retrospective review of patients with airway Candida colonization by bronchial washing or bronchoalveolar lavage. The Candida score was calculated according to the four factors (severe sepsis, surgery at baseline, total parenteral nutrition, and multifocal Candida colonization). Pneumonia related mortality or hopeless discharge expecting death was defined as a poor outcome.ResultsA total of 148 patients were enrolled in the study. In a multivariate analysis model, Candida score was identified as an independent predictor of poor outcomes (odds ratio 2.23; 95% confidential interval 1.57 – 3.17; P <0.001) in pneumonia patients with airway Candida colonization. With a Candida score of three or higher compared with low score group, it was associated with bacterial pneumonia, especially methicillin-resistant Staphylococcus aureus (MRSA) infection (0.0% vs. 15.2%, P = 0.004). In addition, patients with a high Candida score had a longer hospital stay (13 vs. 38 days, P <0.001), longer duration of intensive care (7 vs. 18 days, P <0.001), and higher pneumonia-related mortality (0.0% vs. 45.5%, P <0.001) as compared to the low Candida score group. The Candida score showed a positive correlation with other pneumonia severity scales such as CURB-65 (Confusion, Urea, Respiratory rate, Blood pressure, and age ≥65 years) (r = 0.461, P <0.001), Pneumonia Severity Index (r = 0.397, P <0.001), and predisposition, insult, response, and organ dysfunction (PIRO) score (r = 0.425, P <0.001).ConclusionThis study revealed that Candida is no longer a bystander of airway colonization, and that it affects the progression of bacterial pneumonia, including multidrug-resistant pathogens, particularly MRSA infection. Also Candida score can be used to predict the prognosis of patients with pneumonia.

Modifiable risk factors of ventilator-associated pneumonia in non-intensive care unit versus intensive care unit.

Ventilator-associated pneumonia patients are treated in non-intensive care units because of a shortage of intensive care unit beds in Thailand. Our objective was to assess whether the type of unit and medications prescribed to the patient were associated with ventilator‑associated pneumonia and multidrug resistant ventilator‑associated pneumonia. A matched case-control study nested in a prospective cohort of mechanical ventilation adult patients in a medical-surgical intensive care unit and five non-intensive care units from March 1 through October 31, 2013. The controls were randomly selected 1:1 with cases and matched based on duration and start date of mechanical ventilation. 248 ventilator-associated pneumonia and control patients were analyzed. The most common bacteria were multidrug resistant Acinetobacter baumannii (82.4%). Compared with patients in the intensive care unit, those in the neurosurgical/surgical non-intensive care units were at higher risk (p = 0.278). Proton pump inhibitor was a risk factor (p = 0.011), but antibiotic was a protective factor (p = 0.054). Broad spectrum antibiotic was a risk factor (p < 0.001) for multidrug resistant ventilator-associated pneumonia. Post-surgical and neurosurgical patients treated in non-intensive care unit settings were at the highest risk of ventilator-associated pneumonia. Our findings suggest that alternative using proton pump inhibitors should be considered based on the risk-benefit of using this medication. In addition, careful stewardship of antibiotic use should be warranted to prevent multidrug resistant ventilator-associated pneumonia.

Archimedes Absorbable Internal Biliary Stent in Liver Transplants to Prevent Bile Leak

Biliary complications, especially bile leaks, are an important cause of early postoperative morbidity and, rarely, mortality after liver transplant. The risk is higher in living donor liver transplant (LDLT) compared to deceased donor liver transplant (DDLT). Attempts to reduce bile leaks have included refinements in the biliary anastomosis technique and use of various external and internal stents, with inconsistent benefits. Recent availability and successful use of the absorbable Archimedes stent has prompted its intrabiliary placement across the anastomosis. In this retrospective study, we analyzed the data of 20 adult patients who underwent a liver transplant with duct-to-duct biliary anastomosis using the Archimedes stent. Both DDLT and LDLT were performed using cava-preserving hepatectomy followed by standard implantation methods. Duct-to-duct biliary anastomosis was performed in all cases using interrupted sutures with extracorporeal knots over an absorbable intrabiliary stent. In addition to standard postoperative care, patients were monitored for bile leak. Nine DDLTs had a single anastomosis over a 10-Fr stent. Out of 11 LDLT patients, 7 had a single anastomosis and 4 patients had 2 anastomoses, all over a 6-Fr stent. Two patients died, 1 as a result of graft primary nonfunction and another because of multidrug-resistant pneumonia. One patient had ascending cholangitis owing to stent migration in the duodenum. This episode was treated with endoscopic stent removal and appropriate antibiotics, with good recovery. None of the other patients had bile leaks, biloma, or stent-related complications. Archimedes internal absorbable biliary stents can be safely used in both living and deceased donor liver transplants to prevent bile leaks.

Relationship between Usher Syndrome and Ciliary Dysfunction in a pregnant woman with Multidrug-resistant Pneumonia: A Case Report and Literature Review

Abstract Introduction/Objective Usher syndrome is a rare genetic disorder that consists of auditory and visual disturbances, affecting approximately 4-17 per 100,000 people. In the airways, cilia function in concert with airway mucus for mucociliary clearance, cleansing the airways of inhaled particles and pathogens. Ciliary dysfunction could lead to recurrent pulmonary infections, including from organisms resistant to more than one antibiotic. Few cases have been reported in the literature suggesting a relationship between usher syndrome and ciliary dysfunction. Hence, we would like to report an autopsy case of multidrug-resistant bacterial pneumonia in a pregnant patient with usher syndrome, discussing the possible relationship between usher syndrome, ciliary dysfunction, and multidrug-resistant pneumonia in pregnancy. Methods/Case Report We present a 31-year-old pregnant woman with a history of usher syndrome, hypothyroidism, and hydrocephalus presenting with shortness of breath, cough, and acute respiratory distress syndrome. She further developed refractory hypoxemia and hypercapnia complicated by multidrug-resistant bacteria infection, then intubated. Despite further management of the refractory respiratory failure, she showed no improvement. She was eventually placed on comfort care and died 49 days after she was admitted. Results (if a Case Study enter NA) At autopsy, the pleural surface has exudates and fibrotic adhesion. Both lungs are congested and have consolidations with variable severity on all lobes of both lungs. Microscopically, the most striking finding is the mucin accumulation in large and small airways, even in dilated alveolar spaces. There is evidence of chronic lung injury with significant interstitial fibrosis, diffuse peri-bronchial epithelial metaplasia, also with mucin accumulation. The respiratory epithelium has cilia present. Conclusion Although cilia were present microscopically, their function was not ascertained. The increase in progesterone during pregnancy inhibits cilia beat frequency. Therefore, the hormonal state of pregnancy and the proposed ciliary dysfunction in usher syndrome may worsen the severity of pulmonary infections seen in this patient and eventually caused her death.

Health economics matters in the nanomaterial world: Cost-effectiveness of utilizing an inhalable antibacterial nanomaterial for the treatment of multidrug-resistant pneumonia

Bacterial pathogens rapidly develop resistance to clinically approved antibiotics. Together with the subsiding economic incentives for the development of newer and more effective antibiotic therapies, this threatens to cause a bacterial disease pandemic in the next 30 years. For this reason, timely analyses of various scientific and socioeconomic aspects of alternatives to traditional antibiotic therapies are needed. Here, pharmacoeconomic cost-of-illness, cost-effectiveness and price sensitivity analyses were performed to assess the impact of multidrug resistance of Pseudomonas aeruginosa implicated in pneumonia on healthcare systems of the United States and of the developing countries. The assessment was extended to include the effects of various therapies for this condition, one group of which consisted of colistin administered intravenously or with the use of a nebulizer and another therapy coming in the form of an inhalable colloidal formulation comprising biocompatible antibacterial nanoparticles. Both colistin and nanoparticle therapies produced net gain per quality adjusted life year (QALY) saved for patients with pneumonia caused by multidrug-resistant P. aeruginosa in the United States. In the developing world, in contrast, where the pricing sensitivity is shown to be higher, there is a positive cost of $8800 and $3600 per QALY saved associated with the use of colistin at a price adjusted to the local economy and administered through a parenteral route or through a nebulizer, respectively. Simultaneously, thanks to the higher affordability compensating for the 15% lower clinical efficacy assumed in the model, there is a net gain of $10,100 per QALY saved with the use of the nanoparticle formulation, translating to $52,000 gain for each life saved by the treatment. In conclusion, inorganic nanoparticle therapies for infectious disease are not only more immune to eliciting resistance than small-molecule antibiotics, but are also more applicable in low-cost healthcare systems of the developing world. The current generation of antibiotic therapies is cost-effective in high-cost healthcare systems, such as the one of the United States, but its application in more frugal settings, where pricing is as important as efficacy, comes with tremendous costs. These results demonstrate the considerable disparity in profit margin flexibility depending on the wealth and the size of the healthcare economy, which contributes daily to the widening of the gap between the rich and the poor.

Novelty and nuance in the intensive care unit: new options to combat multidrug resistant pneumonia.

To describe the increasing burden of multidrug resistant (MDR) Gram-negative pathogens in severe pneumonia and to examine the clinical trials supporting a role for novel agents for the treatment of this infection. MDR Gram-negative bacteria cause an increasing proportion of severe pneumonias. Although the epidemiology of resistance varies across the globe, all regions have seen an evolution in resistance, especially among Enterobacterales spp, Pseudomonas aeruginosa, and Acinetobacter bumannii. Fortunately, several clinical trials have established the role for multiple new antibiotics in pneumonia. Although these drugs all have different ranges of in vitro activity and potency, each helps to address the problem of MDR. These studies have varied based on the proportion of subjects undergoing mechanical ventilation and the comparator agents employed. Although all these trials have demonstrated noninferiority to the comparator, the mortality rates across the analyses ranged from <% to >20%. None of the recent investigations included immunocompromised subjects. Multiple new agents exist for treating MDR Gram-negative pneumonia. These agents are not interchangeable. Thus, one must approach their adoption with a nuanced eye.

Factors Associated with Multidrug-Resistant Pathogens in Community-Acquired Pneumonia Patients Hospitalized in a Provincial Teaching Hospital in Indonesia

Background: Pneumonia has high rates of morbidity and mortality in Indonesia. Infections caused by multidrug-resistant (MDR) pathogens are not only found in patients with nosocomial pneumonia but are also reported in patients with community-acquired pneumonia (CAP). Only a few studies have analyzed the factors associated with MDR pathogenic infections, especially in developing countries such as Indonesia. Therefore, the identification of such factors can help to predict the infections caused by MDR pathogens in CAP patients. Objectives: This study aimed to determine factors associated with MDR pathogenic infections in CAP patients admitted to Hasan Sadikin General Hospital, Bandung, West Java Province, Indonesia. Methods: This is an observational analytic study which compared 85 patients with MDR pneumonia and 70 patients with pneumonia caused by non-MDR pathogens from March to May 2018. Sputum of all adults patient &gt; 18 years old with CAP who had the Murray and Washington’s criteria was collected. In vitro test was performed based on the Kirby-Bauer method with Clinical and Laboratory Standards Institute (CLSI) 2018 protocols. This study was ethically approved by the Ethics Committee of the Hasan Sadikin Hospital. Results: One hundred and fifty five patients with positive sputum culture were investigated. Overall, 85 (54%) patients had MDR pathogens in their cultures. Klebsiella pneumoniae was the most common pathogen found in the CAP patients (37/155; 23.9%), while Acinetobacter baumannii accounted for the highest proportion of MDR pathogens (18/85; 21.2%). Multivariate logistic regression analysis showed that the immobilization status was the only associated factor for MDR pathogenic infections in CAP patients (adjusted prevalence ratio = 1.862 [1.432 - 2.420]; P &lt; 0.001). Conclusions: This study highlighted the need for early risk assessment of infections caused by MDR pathogens, especially immobilization status in CAP patients. Also, the local pathogen pattern should be considered to prescribed antibiotics for CAP patients. The findings showed that antibiotics against MDR pathogens should be prescribed for CAP patients with immobilization.

Impact of Multi-Drug-Resistant Pneumonia on Outcomes of Critically Ill Trauma Patients.

Background: Rates of infections with multi-drug-resistant organisms (MDROs) are increasing among critically ill patients. Among non-surgical patients, MDROs increase directly the risk of adverse secondary events including death. However, similar effects do not appear to occur among surgical patients. Specifically, among critically injured trauma patients, it is unknown whether degree of injury versus the presence of an MDRO increases the risk of death. Methods: This is a retrospective chart review of admitted adult trauma patients. Data included demographics, medical comorbidities, injury severity score, infections, occurrence of pneumonia including microbiology sensitivity profile, hospital course, and outcomes. Results: Patients requiring adminission to the intensive care unit (ICU) were more severely injured with greater degree of thoracic and head trauma and had a greater burden of pre-trauma medical comorbidities. Among those admitted to the ICU, 93 patients developed pneumonia. Patients who developed pneumonia were younger and more severely injured, with higher rates of thoracic and head injuries and higher rates of smoking. Development of pneumonia was associated with worse outcomes. However, among patients with pneumonia, comparing MDRO to pan-sensitive (PanSens) infections, PanSens infection occurred earlier and were more likely associated with pre-trauma smoking status. There was no difference in injury patterns, medical comorbidities, or outcomes. Conclusion: The development of pneumonia among trauma patients reflects degree of injury and underlying medical status. However, development of MDRO versus PanSens pneumonia did not affect trauma-related outcomes further. This information will guide family discussions and critical care decisions better among vulnerable trauma patients.

Polymyxin B and Doxycycline for Treatment of Multidrug Resistant Klebsiella Pneumoniae and Staphylococcus Aureus Pneumonia in Intensive Care Unit

Doxycycline is a broad spectrum antibiotic. We hereby report a case report of patients that developed multidrug resistant hospital acquired pneumonia. Patients were treated with Polymyxin B and Doxycycline. From this we want to emphasize that Doxycycline can be used as alternative agent in combination with Polymyxin B for treatment of multidrug resistant pneumonia although there are no large scale studies on combination of Polymyxin B and Doxycycline.

A Multicenter, Prospective, Observational Study to Determine Predictive Factors for Multidrug-Resistant Pneumonia in Critically Ill Adults: The DEFINE Study.

This study was conducted to describe the prevalence, epidemiology, and clinical outcomes of multidrug-resistant (MDR) organism (MDRO) pneumonia in critically ill patients. A multicenter, prospective, observational study of patients admitted to 60 intensive care units (ICUs), from 34 hospitals, in the United States from November to December 2016. Adults (> 18 yrs) receiving antimicrobial therapy at least 5 days for pneumonia were included. Patients were classified into two categories, with or without MDRO, and subcategorized by pneumonia type. Demographics, medication histories, and health care exposure were collected during ICU admission and compared using t test and chi-square tests. Multivariate logistic regression was used to determine predictive factors for MDRO pneumonia and hospital mortality. Of 652 patients, 92 patients (14.1%) developed MDR pneumonia. Predictors of MDRO pneumonia were acid suppression therapy within the previous 90 days (odds ratio [OR] 1.88 [1.14-3.09]; p=0.013), mechanical ventilation (OR 1.96 [1.14-3.35]; p<0.001), and history of MDRO infection (OR 4.74 [2.21-10.18]; p<0.001). Appropriate initial antimicrobial selection occurred in 58 patients (63%) with MDRO pneumonia compared to 464 patients (82.7%) in patients without MDRO pneumonia (p<0.001). MDRO pneumonia was not associated with hospital mortality (18.5% vs 17.6%, p=0.087). In a broad cohort of critically ill patients, MDRO pneumonia is infrequent, and associated with factors describing the intensity of health care provided. Presence of MDRO pneumonia is not associated with hospital mortality. Further study is needed to clarify risk factors for multidrug-resistant pneumonia in critically ill patients.

Treatment of infected lungs by ex vivo perfusion with high dose antibiotics and autotransplantation: A pilot study in pigs.

The emergence of multi-drug resistant bacteria threatens to end the era of antibiotics. Drug resistant bacteria have evolved mechanisms to overcome antibiotics at therapeutic doses and further dose increases are not possible due to systemic toxicity. Here we present a pilot study of ex vivo lung perfusion (EVLP) with high dose antibiotic therapy followed by autotransplantation as a new therapy of last resort for otherwise incurable multidrug resistant lung infections. Severe Pseudomonas aeruginosa pneumonia was induced in the lower left lungs (LLL) of 18 Mini-Lewe pigs. Animals in the control group (n = 6) did not receive colistin. Animals in the conventional treatment group (n = 6) received intravenous application of 2 mg/kg body weight colistin daily. Animals in the EVLP group (n = 6) had their LLL explanted and perfused ex vivo with a perfusion solution containing 200 μg/ml colistin. After two hours of ex vivo treatment, autotransplantation of the LLL was performed. All animals were followed for 4 days following the initiation of treatment. In the control and conventional treatment groups, the infection-related mortality rate after five days was 66.7%. In the EVLP group, there was one infection-related mortality and one procedure-related mortality, for an overall mortality rate of 33.3%. Moreover, the clinical symptoms of infection were less severe in the EVLP group than the other groups. Ex vivo lung perfusion with very high dose antibiotics presents a new therapeutic option of last resort for otherwise incurable multidrug resistant pneumonia without toxic side effects on other organs.

Assessment of Renal Damage in Patients with Multi-Drug Resistant Strains of Pneumonia Treated with Colistin

Background: Treatment of multi-drug-resistant strains of pneumonia with common antibiotics in renal patients is ineffective and physicians are compelled to use Colistin for such cases. Objectives: This study was conducted to assess the mortality, length of stay, and renal damages in the treatment of multi-drugresistant pneumonia with Colistin among multiple trauma patients admitted to the emergency department and transferred to the ICU. Methods: This retrospective cohort study was conducted between 2011 and 2016. 102 multiple trauma (MT) patients with multidrug-resistant strains of hospital-acquired pneumonia (HAP) admitted to the emergency department then transferred to the ICU were assessed. All patients received Colistin according to their weight. Renal damage was evaluated according to the RIFLE criteria. The mortality and the length of stay were assessed. In order to statistically analyze the data, SPSS version 23 software was used to conduct t-test and chi-square test. Results: Out of 102 patients, 55 (54%) died and 50 (49.1%) developed acute renal failure; 64 cases had no hypertension. Patients according to the RIFLE index were assessed: Risk (11.01%), Injury (14%), Failure (18%), Loss (6%), and End-stage renal disease. The prevalence and prognosis of acute kidney injury in multiple trauma patients treated with Colistin were significantly correlated with drug dosage, body mass index, and use of corticosteroids (when assessed using relevant scoring systems, P < 0.05). Conclusions: The use of a scoring system in the intensive care unit, determining those patients requiring Colistin, and adjusting the dosage of this drug for treatment of MT patients with multi-drug resistant strains of HAP are vital. Creatinine levels must be carefully monitored.