scholarly journals Selecting the dosage of ceftazidime–avibactam in the perfect storm of nosocomial pneumonia

2019 ◽  
Vol 76 (3) ◽  
pp. 349-361 ◽  
Author(s):  
Shampa Das ◽  
Diansong Zhou ◽  
Wright W. Nichols ◽  
Andy Townsend ◽  
Paul Newell ◽  
...  
Keyword(s):  
Nosocomial Pneumonia ◽  
Careful Consideration ◽  
Phase Iii ◽  
Antibacterial Drug ◽  
The Usa ◽  
Hospital Acquired Pneumonia ◽  
Hospital Acquired ◽  
Inhibitor Combination ◽  
Perfect Storm ◽  
European Approval

Abstract Purpose Ceftazidime–avibactam is a novel β-lactam/β-lactamase inhibitor combination recently approved in Europe and the USA for the treatment of adults with hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), among other indications. In the phase III REPROVE trial (NCT01808092), ceftazidime–avibactam demonstrated non-inferiority to meropenem for the treatment of patients with nosocomial pneumonia (NP), including VAP. As ceftazidime–avibactam was not studied in patients with NP prior to REPROVE, selecting an appropriate dosage regimen in the “perfect storm” of NP required careful consideration of potential determinants and confounders of response specific to the NP patient population. Methods This review describes the series of preclinical studies and pharmacokinetic/pharmacodynamic (PK/PD) analyses that supported ceftazidime–avibactam dosage selection for patients with NP/VAP (2000/500 mg by 2-h intravenous infusion every 8 h, adjusted for renal function). In parallel, important considerations for antibiotic dosage selection in patients with NP are highlighted, including adequate drug penetration into the lungs, the suitability of murine-derived plasma PK/PD targets, evaluation of MIC distributions against clinical bacterial isolates from patients with NP, and consideration of PK in patients with NP, who are often critically ill. These analyses also supported the European approval of ceftazidime–avibactam for adults with HAP, including VAP, before the completion of REPROVE. Conclusions This work serves as a successful practical example of dosage design for a new antibacterial drug therapy in the indication of NP, including VAP, where previous drug therapies have failed, possibly as a result of evaluation of too few variables, thereby limiting the accuracy of pharmacodynamic predictions.

Hospital-Acquired Pneumonia = Nosocomial Pneumonia

2012 ◽  
pp. 1152-1152
Author(s):  
Jeffrey N. Harr ◽  
Philip F. Stahel ◽  
Phillip D. Levy ◽  
Antoine Vieillard-Baron ◽  
Yang Xue ◽  
...  
Keyword(s):  
Nosocomial Pneumonia ◽  
Hospital Acquired Pneumonia ◽  
Hospital Acquired

Pneumonia

2018 ◽  
Author(s):  
Pippa Newton
Keyword(s):  
Nosocomial Pneumonia ◽  
Acute Infection ◽  
Healthcare Setting ◽  
Community Acquired Pneumonia ◽  
Hospital Acquired Pneumonia ◽  
Pulmonary Parenchyma ◽  
Post Intubation ◽  
Hospital Acquired ◽  
Symptoms And Signs

Pneumonia is defined as acute infection of the pulmonary parenchyma, presenting with consistent symptoms and signs and associated with new radiographic shadowing. It may be acute or chronic in onset and involve either one area of a lung (e.g. lobar pneumonia) or be multifocal in nature. It may be community acquired or hospital acquired. Community- acquired pneumonia is defined as pneumonia occurring in an individual with no recent contact with a healthcare setting, or in a patient admitted to hospital with development of symptoms and/or signs of pneumonia within 48 hours of admission. Hospital-acquired pneumonia or nosocomial pneumonia occurs when a patient develops symptoms or signs of pneumonia after 48 hours of admission to a healthcare setting or in the context of a long-term nursing home resident. A subtype of nosocomial pneumonia is ventilator-associated pneumonia, defined as pneumonia occurring at least 48–72 hours post intubation.

scholarly journals Efficacy of Blind Tracheal Aspirate in Comparison to Bronchoalveolar Lavage for Microbiological Diagnosis of Nosocomial Pneumonia in Patients on Ventilator

2016 ◽  
Vol 4 (2) ◽  
pp. 49-55
Author(s):  
ASM Areef Ahsan ◽  
Mohammad Omar Faruq ◽  
Kaniz Fatema ◽  
Fatema Ahmed ◽  
Shakera Binte Hassan
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Bronchoalveolar Lavage ◽  
Acinetobacter Baumannii ◽  
Nosocomial Pneumonia ◽  
Tracheal Aspirate ◽  
Mechanical Ventilator ◽  
Microbiological Diagnosis ◽  
Hospital Acquired Pneumonia ◽  
Diagnostic Modalities ◽  
Hospital Acquired

Background and Objectives: For diagnosis of nosocomial pneumonia in patients on ventilator, invasive procedure like bronchoscopy for microscopy and quantitative cultures of lower respiratory tract samples is useful but not always possible for potential risk of the procedure and the associated cost. The non-bronchoscopic sampling of the lower airways and quantitative cultures of tracheal aspirate may offer simple and readily available alternative to bronchoscopy with promising results. This study was done to evaluate the efficacy of blind tracheal aspirate in the microbiological diagnosis of nosocomial pneumonia occurring in intubated patients on mechanical ventilator. Materials & Methods: This cross-sectional study was carried out in the Intensive Care Unit in the Department of Critical Care Medicine, BIRDEM Hospital, Dhaka over a period 16 months starting from January 2010 to April 2011. A total of 54 clinically diagnosed cases of nosocomial (hospital acquired) pneumonia who were on ventilator were consecutively included in the study based on predefined enrolment criteria. All the 54 cases were subjected to blind endotracheal aspirate (BTA) followed by bronchoalveolar lavage (BAL) for quantitative cultures of specimens and isolation of causative microorganisms from them. Result: The present study showed that the mean age of the patients was 61 years (range: 24-86 years). Males were predominant in the series with male to female ratio being 7:3. Majority of the patients was haemodynamically stable as indicated by mean blood pressures, heart rate, temperature and respiratory rate. Most (83.3%) of the cases showed significant growth of microbes on culture of blind tracheal aspirates at cut-off value of 105 colony forming unit/ml (cfu/ml), while 87% of the cases exhibited positive growth on culture of bronchoalveolar lavage at cut-off value of 104 cfu/ml. Acinetobacter baumannii was the predominant organism isolated from BTA (73.3%) followed by Pseudomonas aeruginosa (33.3%). An almost similar pattern of growth was evident in BAL with more than 70% being Acinetobacter baumannii and about 30% Pseudomonas aeruginosa. C. albicans. Kiebsiella sp., E. coli, and Flavobacter were less commonly observed in either group. The Kappa test revealed a good agreement (70.7%) between the two procedures suggesting that the two diagnostic modalities are almost comparable in diagnosing pneumonia in patients admitted in ICU (p < 0.001). Conclusion: The study concluded that the accuracy of blind tracheal aspirate and bronchalveolar lavage in the diagnosis of nosocomial pneumonia was fairly comparable. The strength of agreement between the two diagnostic modalities is also good encouraging its use instead of more invasive procedures like BAL in the diagnosis of hospital-acquired pneumonia who are on mechanical ventilator. Ibrahim Cardiac Med J 2014; 4(2): 49-55

scholarly journals Nosocomial Pneumonia in the Era of Multidrug-Resistance: Updates in Diagnosis and Management

2021 ◽  
Vol 9 (3) ◽  
pp. 534
Author(s):  
Elena Xu ◽  
David Pérez-Torres ◽  
Paraskevi C. Fragkou ◽  
Jean-Ralph Zahar ◽  
Despoina Koulenti
Keyword(s):  
Nosocomial Pneumonia ◽  
Multidrug Resistant ◽  
Hospital Acquired Infections ◽  
Recent Developments ◽  
Hospital Acquired Pneumonia ◽  
Polymerase Chain ◽  
Hospital Acquired ◽  
Care Costs ◽  
Microbiological Confirmation

Nosocomial pneumonia (NP), including hospital-acquired pneumonia in non-intubated patients and ventilator-associated pneumonia, is one of the most frequent hospital-acquired infections, especially in the intensive care unit. NP has a significant impact on morbidity, mortality and health care costs, especially when the implicated pathogens are multidrug-resistant ones. This narrative review aims to critically review what is new in the field of NP, specifically, diagnosis and antibiotic treatment. Regarding novel imaging modalities, the current role of lung ultrasound and low radiation computed tomography are discussed, while regarding etiological diagnosis, recent developments in rapid microbiological confirmation, such as syndromic rapid multiplex Polymerase Chain Reaction panels are presented and compared with conventional cultures. Additionally, the volatile compounds/electronic nose, a promising diagnostic tool for the future is briefly presented. With respect to NP management, antibiotics approved for the indication of NP during the last decade are discussed, namely, ceftobiprole medocaril, telavancin, ceftolozane/tazobactam, ceftazidime/avibactam, and meropenem/vaborbactam.

scholarly journals Prospective, Randomized Comparison of Intravenous and Oral Ciprofloxacin with Intravenous Ceftazidime in the Treatment of Nosocomial Pneumonia

1997 ◽  
Vol 8 (2) ◽  
pp. 89-94 ◽  
Author(s):  
Raphael Saginur ◽  
Gary Garber ◽  
Gail Darling ◽  
Stephen Shafran ◽  
William Cameron ◽  
...  
Keyword(s):  
Nosocomial Pneumonia ◽  
Severe Pneumonia ◽  
Comparative Trial ◽  
Similar Efficacy ◽  
University Hospitals ◽  
Gram Positive ◽  
Efficacy Analysis ◽  
Hospital Acquired Pneumonia ◽  
Oral Ciprofloxacin ◽  
Hospital Acquired

OBJECTIVE: To compare the efficacy of intravenous and oral ciprofloxacin and intravenous ceftazidime in the treatment of nosocomial pneumonia.DESIGN: Randomized, nonblinded, multicentre comparative trial.SETTING: Seven Canadian university hospitals.POPULATION: Adult patients with moderate to severe pneumonia developing 72 h or longer after hospitalization.METHODS: After informed consent was obtained, patients were randomized to receive intravenous ciprofloxacin 300 mg every 12 h or ceftazidime 2 g every 8 h. After three days, patients in the ciprofloxacin arm could be switched to oral ciprofloxacin, 750 mg every 12 h. Concomitant clindamycin was allowed for three days in patients with syndromes consistent with Gram-positive or anaerobic infection. Erythromycin could be used if cultures revealed no pathogen.RESULTS: A total of 149 patients were enrolled, of whom 124 were eligible for efficacy analysis. Of 119 pathogens identified in 87 patients, 84 were Gram-negative, and 35 Gram-positive. The mean duration of ciprofloxacin therapy was 12.1 days, of which 9.2 days were given intravenously. Ceftazidime was given for a mean of 9.8 days. There was eradication or reduction of pathogens in 75.7% of ciprofloxacin patients and 70.6% of the ceftazidime group. Clinical resolution or improvement occurred in 87.1% of ciprofloxacin recipients and 87.3% of the ceftazidime group. Eight ciprofloxacin and six ceftazidime patients died. Overall outcomes were considered to be successful in 85.2% of ciprofloxacin patients and 87.1% of ceftazidime recipients. Adverse events were mild.CONCLUSIONS: There were similar efficacy and safety of intravenous and oral ciprofloxacin and intravenous ceftazidime in the treatment of patients with hospital-acquired pneumonia. Physicians were reluctant to use oral therapy in patients.

scholarly journals A post hoc analysis of two Phase III trials showing efficacy and tolerability of ceftobiprole in East Asian patients

2021 ◽  
Author(s):  
Haihui Huang ◽  
Lei Gao ◽  
Marc Engelhardt ◽  
Mikael Saulay ◽  
Kamal Hamed
Keyword(s):  
East Asian ◽  
Phase Iii ◽  
Double Blind ◽  
Post Hoc Analysis ◽  
Asian Patients ◽  
All Cause Mortality ◽  
Hospital Acquired Pneumonia ◽  
Post Hoc ◽  
Hospital Acquired ◽  
East Asian Patients

Aim: To evaluate the efficacy and safety of ceftobiprole in patients from East Asia. Materials & methods: A post hoc analysis was conducted of two randomized, double-blind, Phase III studies in patients with community- or hospital-acquired pneumonia. Results: Findings for East Asian patients were consistent with the overall study populations. A trend toward higher microbiological eradication rates and numerically lower rates of all-cause mortality were reported for ceftobiprole versus comparators (all-cause mortality [intent-to-treat]: community-acquired pneumonia, 1.5 vs 2.8%; hospital-acquired pneumonia excluding ventilator-associated pneumonia, 5.9 vs 11.4%). The incidence of adverse events was similar between treatment groups. Conclusion: This post hoc analysis supports the efficacy and tolerability of ceftobiprole in East Asian patients. ClinicalTrials.gov trial identifiers: NCT00326287 , NCT00210964 , NCT00229008 .

scholarly journals Is ventilated hospital-acquired pneumonia a worse entity than ventilator-associated pneumonia?

2020 ◽  
Vol 29 (157) ◽  
pp. 200023
Author(s):  
Maria Sole Vallecoccia ◽  
Cristina Dominedò ◽  
Salvatore Lucio Cutuli ◽  
Ignacio Martin-Loeches ◽  
Antoni Torres ◽  
...  
Keyword(s):  
Nosocomial Pneumonia ◽  
Significant Proportion ◽  
Final Conclusion ◽  
Ventilator Associated Pneumonia ◽  
Pulmonary Infections ◽  
Specific Flow ◽  
Hospitalised Patients ◽  
Hospital Acquired Pneumonia ◽  
Flow Charts ◽  
Hospital Acquired

IntroductionNosocomial pneumonia develops after ≥48 h of hospitalisation and is classified as ventilator-associated pneumonia (VAP) and hospital-acquired pneumonia (HAP); the latter may require mechanical ventilation (V-HAP) or not (NV-HAP).Main findingsVAP and HAP affect a significant proportion of hospitalised patients and are characterised by poor clinical outcomes. Among them, V-HAP has the greatest 28-day mortality rate followed by VAP and NV-HAP (27.8% versus 18% versus 14.5%, respectively). However, no differences in terms of pathophysiology, underlying microbiological pathways and subsequent therapy have been identified. International guidelines suggest specific flow charts to help clinicians in the therapeutic management of such diseases; however, there are no specific recommendations beyond VAP and HAP classification. HAP subtypes are scarcely considered as different entities and the lack of data from the clinical scenario limits any final conclusion. Hopefully, recent understanding of the pathophysiology of such diseases, as well as the discovery of new therapies, will improve the outcome associated with such pulmonary infections.ConclusionNosocomial pneumonia is a multifaced disease with features of pivotal interest in critical care medicine. Due to the worrisome data on mortality of patients with nosocomial pneumonia, further prospective studies focused on this topic are urgently needed.

scholarly journals Telavancin for Hospital-Acquired Pneumonia: Clinical Response and 28-Day Survival

2014 ◽  
Vol 58 (4) ◽  
pp. 2030-2037 ◽  
Author(s):  
G. Ralph Corey ◽  
Marin H. Kollef ◽  
Andrew F. Shorr ◽  
Ethan Rubinstein ◽  
Martin E. Stryjewski ◽  
...  
Keyword(s):  
Renal Impairment ◽  
Nosocomial Pneumonia ◽  
Severe Renal Impairment ◽  
Survival Rates ◽  
Phase Iii ◽  
Draft Guidance ◽  
Treatment Benefit ◽  
Content Type ◽  
Cure Rates ◽  
Hospital Acquired

ABSTRACTU.S. Food and Drug Administration draft guidance for future antibiotic clinical trials of bacterial nosocomial pneumonia recommends the use of diagnostic criteria according to American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines and the use of a primary endpoint of 28-day all-cause mortality. The effect of applying these guidelines on outcomes of phase III nosocomial pneumonia studies of telavancin was evaluated in apost hocanalysis. ATS/IDSA criteria were applied in a blind fashion to the original all-treated (AT) group. Clinical cure rates at final follow-up were determined in the refined AT and clinically evaluable (CE) groups (ATS/IDSA-AT and ATS/IDSA-CE, respectively). The exploratory endpoint of 28-day survival was evaluated for the ATS/IDSA-AT group. Noninferiority of telavancin versus vancomycin was demonstrated, with similar cure rates in the ATS/IDSA-AT (59% versus 59%) and ATS/IDSA-CE (83% versus 80%) groups. Cure rates favored telavancin in ATS/IDSA-CE patients whereStaphylococcus aureuswas the sole pathogen (86% versus 75%). Overall, 28-day survival rates were similar in the telavancin (76%) and vancomycin (77%) groups but lower in telavancin-treated patients with preexisting moderate-to-severe renal impairment (creatinine clearance [CLCR] of <50 ml/min). Telavancin should be administered to patients with moderate-to-severe renal impairment only if treatment benefit outweighs the risk or if no suitable alternatives are available.

scholarly journals Activity of Telavancin against S. aureus isolated from cystic fibrosis patients including those with decreased susceptibility to Ceftaroline

2018 ◽  
Author(s):  
Melanie Roch ◽  
Maria Celeste Varela ◽  
Agustina Taglialegna ◽  
Warren E. Rose ◽  
Adriana E. Rosato
Keyword(s):  
Cystic Fibrosis ◽  
Galleria Mellonella ◽  
Therapeutic Option ◽  
Infection Model ◽  
Peptidoglycan Synthesis ◽  
Complicated Skin ◽  
The Usa ◽  
Hospital Acquired Pneumonia ◽  
Hospital Acquired

ABSTRACTMethicillin-resistant Staphylococcus aureus (MRSA) acquisition in cystic fibrosis (CF) patients confers a worse clinical outcome with increased rate of declined lung function. Telavancin, an approved lipoglycopeptide used to treat infections due to S. aureus has a dual mode of action causing inhibition of the peptidoglycan synthesis and membrane depolarization. CF-associated MRSA infections remain an important problem with no foreseeable decline in prevalence rates. Although telavancin is currently in clinical use for complicated skin infections and hospital-acquired pneumonia, the activity against CF-associated S. aureus infections has not been investigated. In this work, we studied the activity of telavancin against CF S. aureus strains collected from diverse geographical CF centers in the USA. We found that telavancin-MIC90 was 0.06 μg/ml, 8-fold lower than ceftaroline or daptomycin and 25-fold lower than linezolid and vancomycin. We demonstrate that telavancin at serum-free concentrations has rapid bactericidal activity with a decrease of more than 3 log10 CFU/ml during the first 4 to 6 hours of treatment, performing better in this assay than vancomycin and ceftaroline, including S. aureus resistant to ceftaroline.Telavancin resistance was infrequent (0.3%), although we found that it can occur in-vitro in both CF-and non-CF S. aureus strains by progressive passages with sub-inhibitory concentrations. Genetic analysis of telavancin in-vitro mutants showed gene polymorphisms in cell wall and virulence genes, and increased survival in a Galleria mellonella infection model. Thus, we conclude that telavancin represents a promising therapeutic option for CF infections with potent in-vitro activity and low resistance potential.

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