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This medical industry feature titled, “Exploring a Case in vHABP Care From Physician & Patient Perspectives” is paid for and brought to you by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. This program is intended for health care professionals in the United States, its territories, and Puerto Rico.
Here’s your host, Dr. Joshua Rosenberg.
Welcome. I’m Dr. Joshua Rosenberg, and I’ll be your host for this program today. During this presentation, I’ll discuss the case of a critically ill patient who had a type of bacterial nosocomial pneumonia known as ventilated hospital-acquired bacterial pneumonia, or vHABP, and I’ll focus on some of the key factors we consider in choosing appropriate therapy in such cases. Before I get into the specific details of this case, I’d like to briefly cover the defining characteristics of the different categories of bacterial nosocomial pneumonia and the potential impact on patient outcomes.
Hospital-acquired bacterial pneumonia, or HABP, is bacterial pneumonia that occurs 48 hours or more after hospital admission, which was not incubating at the time of admission and is not associated with mechanical ventilation.1 Ventilated hospital-acquired bacterial pneumonia, or vHABP, is bacterial pneumonia that occurs 48 hours or more after admission, which was not incubating at the time of admission, where that patient subsequently experiences acute respiratory failure and requires ventilation.1,2 Ventilator-associated bacterial pneumonia, or VABP, is bacterial pneumonia that arises more than 48 hours after endotracheal intubation.1
Now, there are a number of key challenges we face when treating critically ill patients with bacterial nosocomial pneumonia. For example, we know that patients with ventilated HABP can have an even higher rate of mortality (up to 39%) than either VABP patients (up to 27%) or HABP patients (up to 22%).3 Also, looking at the organisms commonly found in patients with HABP, vHABP, and VABP, Pseudomonas aeruginosa is one of the most common Gram-negative pathogens associated with cases of HABP/VABP, and it can be particularly challenging to treat in a critically ill patient.4,5
I’ll take a moment now to provide some background details about Elena, a hypothetical patient similar to many patients treated in our intensive care unit and units across the country. Elena is a 73-year-old female Hispanic patient who has type 2 diabetes and hypertension. She came to the ER with symptoms of urinary tract infection—frequency, urgency, dysuria, and suprapubic discomfort as well as fever. The patient indicated that she had a history of recurrent urinary tract infections and was recently treated with an oral antibiotic. The patient was diagnosed with complicated urinary tract infection, or cUTI, and admitted to the hospital. Culture and sensitivity tests later showed 105 colony-forming units/mL of E. coli. We started the patient on IV fluoroquinolone, and after 2 days she was transferred to a subacute rehab unit in our hospital to complete a 7-day course of therapy. After 5 days in the rehab unit, the patient was experiencing respiratory symptoms— cough with green purulent sputum, fever and chills, and shortness of breath—that suggested she had developed hospital-acquired bacterial pneumonia. A chest X-ray showed a right lower lobe infiltrate, so the patient was transferred to a medical floor in the hospital. So now I think would be a good point for us to hear a patient’s perspective.
Hello, my name is Elena. I was born in Puerto Rico and moved to New York with my parents when I was a teenager. I had been working as a home health aide for over 20 years, but I’m now retired. Since my husband passed away 2 years ago, I’ve been living with my daughter and her family and my little dog, Sparky. I’ve had some health problems such as diabetes and high blood pressure, but I’d been doing pretty well until recently, when I began to have some urinary symptoms.
When I became very uncomfortable and started to run a fever, my daughter brought me to the ER. After I was admitted, I was given an antibiotic, and after a few days, I was starting to feel better. However, by the end of the week in the hospital, I started coughing a lot, and I had a fever and was short of breath. I was feeling pretty ill at that point, and I was moved back to the hospital. Over the next day my coughing got even worse, and I was finding it very hard to breathe.
Once back in the hospital, the patient was treated with IV antibiotics for suspected HABP. Her oxygen demands increased, and she was started on high-flow nasal cannula by the floor team. Her sputum was sent for Gram stain and culture. When the Gram stain results came back, they showed abundant Gram-negative rods. After 24 hours, the patient showed evidence of worsening hypoxia, hypotension, respiratory distress, low blood pressure, and hypoxemia. Her blood pressure had dropped to 95/60 mmHg, and her heart rate had increased to 130 beats per minute, and the respiratory rate was 35 breaths per minute. Her oxygen saturation, or SpO2, was 86% despite supplemental oxygen. The patient’s condition was clearly declining, so at this point we moved her to the ICU, where she was intubated, administered 2 liters of fluid, and started on vasopressor therapy. At the time of intubation, a deep tracheal aspirate was taken and sent for culture.
Pseudomonas aeruginosa, a non-lactose fermenter, is one of the most prevalent Gram-negative bacteria in bacterial nosocomial pneumonia.4-7 When choosing her next antibiotic, we considered the possibility that Pseudomonas might be the causative pathogen in this case.
When switching antibiotic therapy, we also consulted the hospital antibiogram, which provides valuable data on the susceptibility of various pathogens, including Pseudomonas, to commonly prescribed antibiotics.
Choosing timely appropriate antibiotic therapy is extremely important in cases of bacterial nosocomial pneumonia, as a delay in effective therapy is associated with an increase in mortality.8 As I mentioned earlier, ventilated HABP patients such as this one have mortality rates that are higher than those of patients with HABP.3 So, the choice of timely appropriate antibiotic therapy is especially important in such cases.
In choosing the next antibiotic to administer to this critically ill patient, I took various factors into account, such as her underlying comorbidities and recent history of both antibiotic use and hospitalization, which puts her at risk for infection. I also considered the most likely causative pathogens, such as Pseudomonas aeruginosa. So, I decided to initiate treatment with ZERBAXA, or ceftolozane and tazobactam, at a dose of 3 grams IV every 8 hours, which is the FDA-approved dose for treatment of adult patients with normal renal function with HABP/VABP.9 The culture and sensitivity results later showed that ZERBAXA clearly was an appropriate option in this case. At this point, I would like to share with you the Indication for ZERBAXA in HABP/VABP and some important safety information.
Important Safety Information ZERBAXA is indicated for the treatment of patients 18 years and older with hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP), caused by the following susceptible Gram-negative microorganisms: Enterobacter cloacae,Escherichia coli, Haemophilus influenzae,Klebsiella oxytoca, Klebsiellapneumoniae, Proteus mirabilis,Pseudomonas aeruginosa, and Serratiamarcescens.
To reduce the development of drug-resistant bacteria and maintain the effectiveness of ZERBAXA and other antibacterial drugs, ZERBAXA should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
Patients with renal impairment: Dose adjustment is required for patients with CrCl 50 mL/min or less. All doses of ZERBAXA are administered over 1 hour. Monitor CrCl at least daily in patients with changing renal function and adjust the dose of ZERBAXA accordingly.
Hypersensitivity: ZERBAXA is contraindicated in patients with known serious hypersensitivity to the components of ZERBAXA (ceftolozane/ tazobactam), piperacillin/tazobactam, or other members of the beta-lactam class. Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving beta-lactam antibacterials. Before initiating therapy with ZERBAXA, make careful inquiry about previous hypersensitivity reactions to cephalosporins, penicillins, or other betalactams. If an anaphylactic reaction to ZERBAXA occurs, discontinue use and institute appropriate therapy.
The efficacy of ZERBAXA in the treatment of HABP/VABP was assessed in a phase 3 randomized clinical trial, known as ASPECT-NP. In this trial, ZERBAXA was compared with meropenem in the treatment of 726 hospitalized adult patients with HABP and VABP. ASPECT NP was unique among bacterial nosocomial pneumonia registration trials in that all patients were mechanically ventilated upon randomization. In addition, 92% of the patients in this trial were treated in the ICU, 77% had been hospitalized for 5 days or longer, and 49% were ventilated for 5 days or longer.9,10
In this trial, ZERBAXA achieved the primary efficacy endpoint of noninferiority to meropenem in Day 28 all cause mortality.9 In the subgroup of patients with ventilated HABP, there was a favorable response to ZERBAXA in Day 28 all-cause mortality, which was 24.2% for patients treated with ZERBAXA compared with 37% for the meropenem-treated patients.9 In the patients with VABP, the Day 28 all-cause mortality rate for patients treated with ZERBAXA was 24% compared with 20.3% for the meropenem-treated patients.9
Let’s take a moment now to consider some additional safety information for ZERBAXA.
Clostridioides difficile-associated diarrhea (CDAD), ranging from mild diarrhea to fatal colitis, has been reported with nearly all systemic antibacterial agents, including ZERBAXA. Careful medical history is necessary because CDAD has been reported to occur more than 2 months after the administration of antibacterial agents. If CDAD is confirmed, antibacterial use not directedagainst C. difficile should be discontinued, if possible.
Development of drug-resistant bacteria: Prescribing ZERBAXA in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and risks the development of drug-resistant bacteria.
Adverse reactions: The most common adverse reactions occurring in ≥5% of patients in the HABP/VABP trial were hepatic transaminase increased (11.9%), renal impairment/renal failure (8.9%), and diarrhea (6.4%).
So, now, I’ll conclude this presentation by noting that based on the clinical trial results, ZERBAXA starting at a dosage of 3 grams every 8 hours, and appropriately adjusted for renal function when indicated, might also be an appropriate option to consider for other critically ill patients with nosocomial bacterial pneumonia caused by susceptible Gram-negative pathogens.9 I hope you have found the presentation today informative, and I thank you very much for your participation. Before prescribing ZERBAXA, please read the accompanying Prescribing information at merck.com:
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1. Kalil AC, et al. Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis. 2016;63:e61-e111.
2. US Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research
(CDER). FDA Guidance for Industry. Hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia: developing drugs for treatment. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/hospital-acquired-bacterial-pneumonia-and-ventilator-associated-bacterial-pneumonia-developing-drugs. Published May 2014. Updated June 2020. Accessed September 9, 2021.
3. Talbot GH, et al. Evidence-based study design for hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia. J Infect Dis. 2019;219:1536-1544.
4. Schreiber MP, et al. Challenges and opportunities in the treatment of ventilator-associated pneumonia. Expert Rev Anti Infect Ther. 2017;15(1):23-32.
5. Cilloniz C, et al. Microbial etiology of pneumonia: epidemiology, diagnosis and resistance patterns. Int J Mol Sci. 2016;17:2120.
6. Columbia University. A brief classification of Gram-negative rods.
http://www.columbia.edu/itc/hs/medical/pathophys/id/2008/utiGNR.pdf. Accessed September 9, 2021.
7. Data available on request from Merck, Professional Services-DAP, WP1-27, PO Box 4, West Point, PA 19486-0004. USZER-00925.
8. Tsalik EL, et al. Potential cost-effectiveness of early identification of hospital-acquired Infection in critically ill patients. Ann Am Thorac Soc. 2016;13(3):401-413.
9. ZERBAXA (ceftolozane and tazobactam) Prescribing Information. Merck Sharp & Dohme Corp., a subsidiary of Merck & Co.,Inc.
10. Kollef MH, et al. Ceftolozane/tazobactam versus meropenem for treatment of nosocomial pneumonia (ASPECT-NP): a randomised, controlled, double‐blind, phase 3, non-inferiority trial. Lancet Infect Dis. 2019;19:1299-1311.