scholarly journals Clinical Implications of Microbiologic Treatment Failure in the Setting of Clinical Cure of Bacterial Pneumonia

2019 ◽  
Author(s):  
Owen R Albin ◽  
Oryan Henig ◽  
Twisha S Patel ◽  
Thomas S Valley ◽  
Jason M Pogue ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Clinical Cure ◽  
Bacterial Pneumonia ◽  
Acute Illness ◽  
Therapeutic Interventions ◽  
Comorbid Conditions ◽  
Recurrent Pneumonia ◽  
Ventilator Dependence ◽  
Immunocompromised Status ◽  
Cure Rates

Abstract Background Microbiologic cure is a common outcome in pneumonia clinical trials, but its clinical significance is incompletely understood. Methods We conducted a retrospective cohort study of adult patients hospitalized with bacterial pneumonia who achieved clinical cure. Rates of recurrent pneumonia and death were compared between patients with persistent growth of the index pathogen at the time of clinical cure (microbiologic failure) and those with pathogen eradication (microbiologic cure). Results Among 441 patients, 237 experienced microbiologic cure and 204 experienced microbiologic failure. Prevalences of comorbidities, ventilator dependence, and severity of acute illness were similar between groups. Patients with microbiologic failure experienced significantly higher rates of recurrent pneumonia or death following clinical cure than patients with microbiologic cure, controlling for comorbid conditions, severity of acute illness, appropriateness of empiric antibiotics, intensive care unit placement, tracheostomy dependence, and immunocompromised status (90-day multivariable adjusted odds ratio [OR], 1.56; 95% confidence interval [CI], 1.04–2.35). This association was observed among patients with pneumonias caused by Staphylococcus aureus (90-day multivariable adjusted OR, 3.69; 95% CI, 1.73–7.90). A trend was observed among pneumonias caused by nonfermenting gram-negative bacilli, but not Enterobacteriaceae or other pathogens. Conclusions Microbiologic treatment failure was independently associated with recurrent pneumonia or death among patients with bacterial pneumonia following clinical cure. Microbiologic cure merits further study as a metric to guide therapeutic interventions for patients with bacterial pneumonia.

scholarly journals Ceftolozane/tazobactam probability of target attainment and outcomes in participants with augmented renal clearance from the randomized phase 3 ASPECT-NP trial

Critical Care ◽  
2021 ◽  
Vol 25 (1) ◽  
Author(s):  
Andrew F. Shorr ◽  
Christopher J. Bruno ◽  
Zufei Zhang ◽  
Erin Jensen ◽  
Wei Gao ◽  
...  
Keyword(s):  
Renal Function ◽  
Normal Renal Function ◽  
Clinical Cure ◽  
Bacterial Pneumonia ◽  
Target Attainment ◽  
Augmented Renal Clearance ◽  
Phase 3 ◽  
Epithelial Lining Fluid ◽  
All Cause Mortality ◽  
Cure Rates

Abstract Background The randomized, double-blind, phase 3 ASPECT-NP trial evaluated the efficacy of 3 g of ceftolozane/tazobactam (C/T) versus 1 g of meropenem infused every 8 h for 8 to 14 days for treatment of adults with hospital-acquired bacterial pneumonia (HABP) or ventilator-associated bacterial pneumonia (VABP). We assessed the probability of target attainment and compared efficacy outcomes from ASPECT-NP in participants with augmented renal clearance (ARC) versus those with normal renal function. Methods Baseline renal function was categorized as normal renal function (creatinine clearance 80–130 mL/min) or ARC (creatinine clearance > 130 mL/min). Population pharmacokinetic models informed Monte Carlo simulations to assess probability of target attainment in plasma and pulmonary epithelial lining fluid. Outcomes included 28-day all-cause mortality and clinical cure and per-participant microbiologic cure rates at the test-of-cure visit. Results A > 99% and > 80% probability of target attainment was demonstrated for ceftolozane and tazobactam, respectively, in simulated plasma and epithelial lining fluid. Within treatment arms, 28-day all-cause mortality rates in participants with normal renal function (C/T, n = 131; meropenem, n = 123) and ARC (C/T, n = 96; meropenem, n = 113) were comparable (data comparisons presented as rate; treatment difference [95% CI]) (C/T: normal renal function, 17.6%; ARC, 17.7%; 0.2 [− 9.6 to 10.6]; meropenem: normal renal function, 20.3%; ARC, 17.7%; − 2.6 [− 12.6 to 7.5]). Clinical cure rates at test-of-cure were also comparable across renal function groups within treatment arms (C/T: normal renal function, 57.3%; ARC, 59.4%; − 2.1 [− 14.8 to 10.8]; meropenem: normal renal function, 59.3%; ARC, 57.5%; 1.8 [− 10.6 to 14.2]). Per-participant microbiologic cure rates at test-of-cure were consistent across renal function groups within treatment arms (C/T: normal renal function, 72.2% [n/N = 70/97]; ARC, 71.4% [n/N = 55/77]; 0.7 [− 12.4 to 14.2]; meropenem: normal renal function, 75.0% [n/N = 66/88]; ARC, 70.0% [n/N = 49/70]; 5.0 [− 8.7 to 19.0]). Conclusions C/T and meropenem resulted in 28-day all-cause mortality, clinical cure, and microbiologic cure rates that were comparable between participants with ARC or normal renal function. In conjunction with high probability of target attainment, these results confirm that C/T (3 g) every 8 h is appropriate in patients with HABP/VABP and ARC. Trial registration ClinicalTrials.gov identifier: NCT02070757, registered February 25, 2014; EudraCT: 2012-002862-11.

scholarly journals 2222. Impact of Empiric Aminoglycoside Usage on Outcomes in Bacterial Pneumonia

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S758-S758
Author(s):  
Owen Albin ◽  
Twisha S Patel ◽  
Oryan Henig ◽  
Thomas Valley ◽  
Jason M Pogue ◽  
...  
Keyword(s):  
Serum Creatinine ◽  
Clinical Cure ◽  
Bacterial Pneumonia ◽  
Kidney Injury ◽  
Hospitalized Patients ◽  
Recurrent Pneumonia ◽  
Absolute Increase ◽  
Aminoglycoside Therapy ◽  
Healthcare Associated ◽  
The Impact

Abstract Background Although aminoglycosides are recommended as part of empiric combination therapy in selected patients with healthcare-associated pneumonia, their efficacy and safety remains unclear. The objectives of this study were to evaluate the impact of empiric aminoglycoside treatment on microbiologic cure, recurrent pneumonia and death, and acute kidney injury (AKI) among hospitalized patients treated for pneumonia who were clinically cured. Methods This was a nested cohort study including 441 hospitalized subjects with confirmed bacterial pneumonia who achieved clinical cure. All subjects had positive respiratory cultures at the beginning of therapy and also had cultures obtained at the time of antibiotic completion. Subjects with the same pathogen present at both the beginning of and at the end of treatment were categorized as microbiologic failure and all others were categorized as microbiologic cure. Serum creatinine was measured at both the beginning and end of therapy, with an absolute increase in serum creatinine of 0.5 mg/L or greater defined as AKI. Composite outcomes of 30- and 90-day recurrent pneumonia or death following the clinical cure of the index pneumonia were captured. Patients who received empiric aminoglycoside therapy were compared with patients who did not receive aminoglycoside therapy. Results Of 441 included subjects, 14.5% (N = 64) received aminoglycoside therapy and 85.5% (N = 377) did not. The mean age was 54.7 years, with 70.5% male and 78.2% white. Characteristics of the two groups (including Charlson Comorbidity Indices and APACHE II scores) were similar. Rates of microbiologic cure, death/recurrent pneumonia at 30- and 90-days and AKI and were similar in both groups (table). In subgroup analyses restricted to different pathogen groups these associations remained unchanged. Conclusion Among hospitalized patients with pneumonia who were clinically cured, empiric aminoglycoside therapy was not associated with an increased likelihood of microbiologic cure, death or recurrent pneumonia or AKI. Disclosures All authors: No reported disclosures.

scholarly journals Effectiveness and safety of ciclopirox olamine in patients with dermatophytosis: a retrospective cohort analysis

2020 ◽  
Vol 7 (1) ◽  
pp. 38
Author(s):  
Vinay Saraf ◽  
Satyaprakash Mahajan ◽  
Gaurav Deshmukh ◽  
Dhiraj Dhoot ◽  
Hanmant Barkate
Keyword(s):  
Treatment Failure ◽  
Clinical Cure ◽  
Retrospective Cohort ◽  
Antifungal Agents ◽  
Topical Therapy ◽  
Cohort Analysis ◽  
Cure Rate ◽  
Ciclopirox Olamine ◽  
Treatment Naïve ◽  
Cure Rates

<p class="abstract"><strong>Background:</strong> The current scenario of dermatophytosis is alarming, despite the availability of multiple antifungal agents the management of dermatophytosis is still challenging. Hence there is a need for a different antifungal with a novel mechanism of action for the management of dermatophytosis.</p><p class="abstract"><strong>Methods: </strong>It was retrospective cohort study where in record of patients with dermatophytosis who were candidates for topical therapy only were analysed. All the patients were treated with Ciclopirox olamine 1% twice daily for 6 weeks. The efficacy end points were complete cure rate, mycological cure rate and clinical cure rate.</p><p class="abstract"><strong>Results: </strong>613 patients were included in the final analysis. At the end of study period the complete, mycological and clinical cure rates were 73.89%, 75.37% and 77.65% respectively. Out of 613 patients included 528 patients showed treatment failure to previous topical antifungal agents while 84 patients were treatment naïve. In treatment failure patients the complete, mycological and clinical cure rates were 72.15%, 73.48, and 75.56% respectively. In treatment naïve patients the complete, mycological and clinical cure rates were 84.70%, 87.05% and 90.58% respectively. 5.70% reported adverse events. The most common adverse event was pruritus followed erythema, dryness and rash.</p><p><strong>Conclusions: </strong>Results of this study proves that ciclopirox is efficacious and safe in the management of dermatophytosis. This study also proves that ciclopirox is useful in those patients who failed to respond to other topical antifungal agents. </p>

scholarly journals Clinical and Microbiologic Outcomes in Patients with Monomicrobial Stenotrophomonas maltophilia Infections

2019 ◽  
Vol 63 (11) ◽  
Author(s):  
Cara Nys ◽  
Kartik Cherabuddi ◽  
Veena Venugopalan ◽  
Kenneth P. Klinker
Keyword(s):  
Nosocomial Infections ◽  
Clinical Cure ◽  
Stenotrophomonas Maltophilia ◽  
Opportunistic Pathogen ◽  
Content Type ◽  
High Cure ◽  
Resistance Selection ◽  
Biofilm Production ◽  
Cure Rates

ABSTRACT Stenotrophomonas maltophilia is an opportunistic pathogen observed in nosocomial infections. Due to biofilm production and resistance to numerous antimicrobials, eradication is difficult. This study evaluated outcomes for monomicrobial S. maltophilia infections. Seventy-six patients were included, with 45 patients on trimethoprim-sulfamethoxazole and 31 patients on levofloxacin. Overall clinical cure, microbiological eradication, and 28-day mortality were observed in 79%, 82%, and 14% of patients, respectively. The use of trimethoprim-sulfamethoxazole or levofloxacin resulted in high cure rates; however, a trend toward resistance selection with levofloxacin was identified.

scholarly journals Clinafloxacin versus Piperacillin-Tazobactam in Treatment of Patients with Severe Skin and Soft Tissue Infections

2001 ◽  
Vol 45 (2) ◽  
pp. 525-531 ◽  
Author(s):  
G. Siami ◽  
N. Christou ◽  
I. Eiseman ◽  
K. J. Tack
Keyword(s):  
Soft Tissue ◽  
Adverse Events ◽  
Clinical Cure ◽  
Wound Infections ◽  
Soft Tissue Infections ◽  
Pathogenic Species ◽  
Treatment Groups ◽  
Diabetic Foot Infections ◽  
Cure Rates ◽  
To Receive

ABSTRACT Patients (n = 409) with severe skin and soft tissue infections (SSTIs) were randomized to receive clinafloxacin or piperacillin-tazobactam (plus optional vancomycin for methicillin-resistant cocci), administered intravenously, with the option to switch to oral medication. Most patients had cellulitis, wound infections, or diabetic foot infections. Staphylococcus aureus, Enterococcus faecalis, and Pseudomonas aeruginosa were the most common baseline pathogens. Fewer baseline pathogens were resistant to clinafloxacin (1.8%) than to piperacillin-tazobactam (6.2%) (P = 0.001). The clinafloxacin and piperacillin-tazobactam groups did not differ significantly in clinical cure rates (68.8 and 65.2%, respectively) or microbiologic eradication rates (61.5 and 57.2%). Clinafloxacin yielded higher eradication rates for all three of the most common pathogenic species, although no differences were statistically significant. Within the power of this study, the overall frequency of adverse events was similar (P = 0.577) in the two treatment groups. Drug-associated adverse events (P = 0.050) and treatment discontinuations (P = 0.052) were marginally more frequent in the clinafloxacin group, primarily due to phototoxicity in outpatients receiving clinafloxacin. Although most cases of phototoxicity were mild to moderate, four cases were reported as severe. In summary, clinafloxacin monotherapy was equivalent in effectiveness to therapy with piperacillin-tazobactam plus optional vancomycin in the treatment of hospitalized patients with severe SSTIs.

scholarly journals Retrospective Analysis of Clinical and Cost Outcomes Associated with Methicillin-ResistantStaphylococcus aureusComplicated Skin and Skin Structure Infections Treated with Daptomycin, Vancomycin, or Linezolid

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Bradley M. Wright ◽  
Edward H. Eiland
Keyword(s):  
Antibiotic Therapy ◽  
Retrospective Analysis ◽  
Clinical Cure ◽  
Adverse Drug Events ◽  
Treatment Options ◽  
Skin Structure ◽  
Complicated Skin ◽  
Cure Rates ◽  
Cost Outcomes ◽  
Length Of Hospitalization

Objective. The objective of this analysis was to compare clinical and cost outcomes associated with patients who had suspected or documented methicillin-resistantStaphylococcus aureus(MRSA) infections treated with daptomycin, vancomycin, or linezolid in complicated skin and skin structure infections (cSSSIs).Design. This was a retrospective analysis conducted from February to June of 2007. Appropriate data was collected, collated, and subsequently evaluated with the purpose of quantifying length of stay, antibiotic therapy duration, clinical cure rates, adverse drug events, and cost of hospitalization.Results. All 82 patients included in the analysis experienced clinical cure. The duration of antibiotic therapy was similar among the three groups yet the length of hospitalization was slightly shorter in the daptomycin group.Conclusions. The incidence of resistant staphylococcal infections is increasing; therefore, judicious use of MRSA active agents is paramount. Future studies are necessary to determine if MRSA treatment options can be stratified based on the severity of the infectious process.

scholarly journals Prospective Study of the Wilson Severity-of-Illness Scoring System for Complicated Skin and Skin Structure Infections

2012 ◽  
Vol 57 (1) ◽  
pp. 647-650 ◽  
Author(s):  
George H. Talbot ◽  
Tanya O'Neal ◽  
Anita F. Das ◽  
Dirk Thye
Keyword(s):  
Clinical Cure ◽  
Clinical Cure Rate ◽  
Severity Of Illness ◽  
Cure Rate ◽  
Two Phase ◽  
Ceftaroline Fosamil ◽  
Risk Class ◽  
Skin Structure ◽  
Complicated Skin ◽  
Cure Rates

ABSTRACTWilson et al. (Am. J. Surg.185:369–375, 2003) developed a disease severity classification system for use in complicated skin and skin structure infections (cSSSI). Two phase 3 trials of ceftaroline fosamil in cSSSI provided the opportunity to evaluate the association between Wilson Severity Risk Class and clinical cure rates. Our analyses did not confirm that an association exists between Wilson Severity Risk Class and clinical cure rate and, thus, did not validate its predictive utility.

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