Comparison of clinical cure rates in adults with ventilator-associated pneumonia treated with intravenous ceftazidime administered by continuous or intermittent infusion: A retrospective, nonrandomized, open-label, historical chart review (original) (raw)

Continuous infusion versus intermittent infusion of ceftazidime for the treatment of pneumonia caused by Pseudomonas aeruginosa

Critical Care, 2005

Introduction Community-acquired pneumonia remains a common condition worldwide. It is associated with significant morbidity and mortality. The aim of this study was to evaluate conditions that could predict a poor outcome. Design Retrospective analyse of 69 patients admitted to the ICU from 1996 to 2003. Demographic data included age, sex and medical history. Etiologic agents, multiorgan dysfunction, nosocomial infections, SAPS II and PORT scores were recorded for each patient. For statistical analysis we used a t test, chi-square test and Mann-Whitney U test on SPSS ®. A value of P less than 0.05 was considered significant. Results Forty-seven patients were male and 22 patients were female. Mean age was 52 years. Sixty-seven percent had serious pre-morbid conditions including pulmonary disease (34.8%), cardiac problems (36.2%), diabetes (13%) and chronic liver disease (5.8%); 40.6% were smokers, drug abusers or alcohol dependents. Sixtyeight patients required invasive mechanical ventilation. The average length of ventilation was 13.5 days, median 8 days. The mean SAPS II score was 40.14 and the mean PORT score was 141. The mortality rate was 27.5% (SAPS II estimated mortality, 35%). Complications reported were ARDS (40.6%), septic shock (34.8%), acute renal failure (2.9%), cardiac arrest (8.7%) and nosocomial infeccions (46.4%). Mortality rates were higher for previous hepatic (75%) and metabolic (33%) diseases. We found a close association between crude mortality and SAPS II score (P = 0.003) and development of complications (P = 0.0028). Respiratory dysfunction (P = 0.006) and septic shock (P = 0.022) were most significantly related to mortality. No significant differences were founded regarding age, comorbidities, PORT score, etiologic agents, nosocomial infections and length of invasive mechanical ventilation. Conclusions Previous hepatic chronic disease was strictly related to higher mortality as well as isolation of MRSA. ARDS and septic shock predicted a poor outcome. SAPS II score was the best severity indicator of mortality. P2 Closed endotracheal suction system without periodic change versus open endotracheal system

Ceftolozane/tazobactam versus colistin in the treatment of ventilator-associated pneumonia due to extensively drug-resistant Pseudomonas aeruginosa

Scientific Reports, 2022

Resistant strains of Pseudomonas aeruginosa are common pathogens in the intensive care unit (ICU), limiting available therapeutic options. We aimed to compare ceftolozane/tazobactam (C/T) with colistimethate sodium (CMS) in the treatment of ventilator-associated pneumonia (VAP) due to extensively drug-resistant (XDR) Pseudomonas aeruginosa. A retrospective, observational study was performed at a tertiary care ICU. Clinical and microbiological success rate, 28-day all-cause mortality, and adverse events were compared in patients who received C/T with those treated with systemic CMS. A total of 51 patients were included (18 in the C/T and 33 in the CMS group). Clinical success rates in the C/T and CMS groups were 13 (72.2%) and 10 (30.3%), respectively. On multivariate regression analysis, treatment with C/T was independently associated with clinical success (odds ratio 4.47, 95% CI 1.17–17.08). There was no difference in 28-day all-cause mortality (27.8% and 33.3% in the C/T and CMS ...

Nebulized Ceftazidime and Amikacin in Ventilator-associated Pneumonia Caused by Pseudomonas aeruginosa

American Journal of Respiratory and Critical Care Medicine, 2011

Rationale: In experimental pneumonia, nebulization of antibiotics provides high lung tissue concentrations and rapid bacterial killing. Objectives: To assess efficacy and safety of nebulized ceftazidime and amikacin in ventilator-associated pneumonia caused by Pseudomonas aeruginosa. Methods: Forty patients with ventilator-associated pneumonia caused by Pseudomonas aeruginosa were included in a randomized comparative phase II trial. Twenty patients infected by susceptible or intermediate strains, received nebulized ceftazidime (15 mg.kg-1 .3h-1) and amikacin (25 mg.kg-1 .day-1). Seventeen patients infected by susceptible strains received intravenous ceftazidime (90 mg.kg-1 .day-1 , continuous administration) and amikacin (15 mg.kg-1 .day-1). In 3 patients infected by intermediate strains, amikacin was replaced by ciprofloxacin (400 mg.12 h-1). Measurements and Main Results: After 8 days of antibiotic administration, aerosol and intravenous groups were similar in terms of successful treatment (70% vs 55%), treatment failure (15% vs 30 %) and superinfection by other micoorganisms (15% vs 15%). Antibiotic-induced changes in lung computed tomography aeration were not different between groups (increase in gas volume=159 ± 460 ml vs 251 ± 583 ml; decrease in tissue volume=-58 (-77-25) ml vs-89 (-139-5) ml). Acquisition of pertreatment antibiotic resistance was observed exclusively in intravenous group. In aerosol group, 4 patients infected by intermediate strains were successfully treated. Nebulization induced an obstruction of expiratory filter in 3 patients. The obstruction caused cardiac arrest in 1 patient who fully recovered after brief cardiopulmonary resuscitation. Conclusion: Nebulization and intravenous infusion of ceftazidime and amikacin provide similar efficiency for treating ventilator-associated pneumonia caused by Pseudomonas aeruginosa. Nebulization is efficient against intermediate strains and may prevent per-treatment acquisition of antibiotic resistance.

Ceftolozane/Tazobactam Versus Colistin in the Treatment of Ventilator-Associated Pneumonia Due to Extensively Drug-Resistant Pseudomonas Aeruginosa: A Comparative Cohort Study

2021

Background: Pseudomonas aeruginosa is a common pathogen in the intensive care unit (ICU). Resistant strains are frequently isolated, leaving colistimethate sodium (CMS), the drug with known toxicity and questionable pharmacokinetics, as the last-line conventional therapeutic option.The new cephalosporin and β-lactamase inhibitor combinations like ceftolozane/tazobactam (C/T) expanded the available antibiotics for Gram-negative infections. We aimed to compare C/T with CMS in the treatment of ventilator-associated pneumonia (VAP) due to extensively drug-resistant (XDR) Pseudomonas aeruginosa. Methods: A retrospective, observational study was performed at a tertiary care ICU. Patients with VAP due to XDR Pseudomonas aeruginosa were enrolled. Clinical and microbiological success rate, 28-day all-cause mortality, and adverse events were compared in patients who received C/T with those treated with systemic CMS. Multivariate logistic regression was performed to identify predictors of clin...

Efficacy of the combination of levofloxacin plus ceftazidime in the treatment of hospital-acquired pneumonia in the Intensive Care Unit

International Journal of Antimicrobial Agents, 2006

To investigate the efficacy and tolerability of treatment with a combination of levofloxacin and ceftazidime in Gram-negative hospitalacquired pneumonia (HAP) in the Intensive Care Unit (ICU), we performed a prospective, open-label, non-comparative, 1-year study in an Italian ICU. Patients received levofloxacin 500 mg twice a day intravenously plus ceftazidime 2 g three times a day intravenously for 7-14 days. Primary efficacy variables were clinical and microbiological responses at test-of-cure visit. Twenty-one patients were enrolled. Pseudomonas aeruginosa and Klebsiella pneumoniae were the most frequently identified pathogens. Clinical success was achieved in 17/21 clinically evaluable patients (81%) and in 12/15 microbiologically evaluable patients (80%). Regarding only the group with ventilator-associated pneumonia, cure was achieved in 10/14 clinically evaluable patients (71%) and in 11/14 microbiologically evaluable patients (79%). Therapy was well tolerated. We conclude that this combination regimen is safe and clinically and microbiologically efficacious in the treatment of Gram-negative HAP.

Empiric, Broad-Spectrum Antibiotic Therapy with an Aggressive De-Escalation Strategy Does Not Induce Gram-Negative Pathogen Resistance in Ventilator-Associated Pneumonia

Surgical Infections, 2010

Background: Early, empiric, broad-spectrum antibiotics followed by de-escalation to pathogen-specific therapy is the standard of care for ventilator-associated pneumonia (VAP). In our surgical intensive care unit (SICU), imipenem-cilastatin (I-C) in combination with tobramycin (TOB) or levofloxacin (LEV) has been used until quantitative bronchoalveolar lavage results are finalized, at which time de-escalation occurs to pathogen-specific agents. With this practice, however, alterations in antimicrobial resistance remain a concern. Our hypothesis was that this strict regimen does not alter antimicrobial susceptibility of common gram-negative VAP pathogens in our SICU. Methods: After Institutional Review Board approval, a retrospective review of SICU-specific antibiograms was performed for the sensitivities of common gram-negative VAP pathogens. Time periods were defined as early (January-June 2005) and late (July-December 2006). Chart review of empiric and de-escalation antibiotic usage was obtained. Data were collated, and statistical significance was assessed with the chi-square test using the online Simple Interactive Statistical Analysis tool. Results: Imipenem-cilastatin was used 198 times for empiric VAP coverage (811 patient-days), whereas TOB and LEV were given a total of 149 (564 patient-days) and 61 (320 patient-days) times, respectively. Collectively, the susceptibility of gram-negative organisms to I-C did not change (early 91.4%; late 97%; p ¼ 0.33). Individually, non-significant trends to greater sensitivity to I-C were noted for both Pseudomonas aeruginosa (early 85.7%; late 90.9%; p ¼ 0.73) and Acinetobacter baumannii (early 80%; late 100%; p ¼ 0.13). Further, both TOB (early 77.1%; late 70.0%; p ¼ 0.49) and LEV (early 74.3%; late 70.0%; p ¼ 0.67) were found to maintain their susceptibility profiles. The frequency of resistant gram-positive VAPs was unchanged during the study period. Our de-escalation compliance (by 96 h) was 78% for I-C, 77.2% for TOB, and 59% for LEV. When infections requiring I-C were removed from the analysis, de-escalation compliance was improved to 92%. Conclusions: In our SICU, early, empiric broad-spectrum VAP therapy followed by de-escalation to pathogenspecific agents did not alter antimicrobial resistance and is a valid practice. Further, our compliance with deescalation practices was higher than published rates. V entilator-associated pneumonia (VAP) is a common nosocomial infection that arises 48-72 h after endotracheal intubation and is the leading cause of morbidity and death in the surgical intensive care unit (SICU) [1,2]. The incidence (10-30% of intubated patients) differs greatly depending on patient risk factors, and the attributable mortality rate (approximately 30-50%) increases when more virulent or resistant organisms are involved [3-5]. The mortality rate is increased further if inadequate empiric antimicrobial therapy is initiated or proper treatment is delayed

Microbial Profile and Antibiotic Susceptibility Patterns of Pathogens Causing Ventilator- Associated Pneumonia at Intensive Care Unit, Sestre Milosrdnice University Hospital Center, Zagreb, Croatia

PubMed, 2015

Ventilator-associated pneumonia (VAP) is very common in many intensive care Units, but there are still many uncertainties about VAP, especially about the choice of initial empiric antibiotics. The incidence of specific pathogens with different susceptibility patterns causing VAP varies from hospital to hospital. This is the reason why empiric initial antibiotic treatment for VAP should be based not only on general guidelines (that recommend therapy according to the presence of risk factors for multidrug-resistant bacteria), but also on up-to-date information on local epidemiology. The aim of this study was to determine the microbial profile of pathogens causing VAP and their antibiotic susceptibility patterns. The study was conducted in the 15-bed surgical and neurosurgical Intensive Care Unit, Department of Anesthesiology and Intensive Care, Sestre milosrdnice University Hospital Center, Zagreb, Croatia. Retrospective data were collected from September 2009 to March 2013. All patients that developed VAP during the study period were eligible for the study. According to study results, the incidence of VAP was 29.4%. The most commonly isolated bacterium was Staphylococcus aureus (21.1%), followed by Pseudomonas aeruginosa (19.0%) and Acinetobacter species (13.6%). All Staphylococcus aureus isolates were susceptible to vancomycin and linezolid. Pseudomonas aeruginosa showed 100% susceptibility to cefepime and very high susceptibility to pip'eracillin-tazobactam (96%), ceftazidime (93%) and ciprofloxacin (89%). Ampicillin-sulbactam was highly effective for Acinetobacter species, showing resistance in only 8% of isolates. In conclusion, according to study data, appropriate empiric antibiotic therapy for patients with VAP without risk factors for multidrug-resistant bacteria is ceftriaxone and for patients with risk factors for multidrug-resistant bacteria ampicillin-sulbactam plus cefepime plus vancomycin or linezolid.

Comparison of -lactam regimens for the treatment of Gram-negative pulmonary infections in the intensive care unit based on pharmacokinetics/pharmacodynamics

Journal of Antimicrobial Chemotherapy, 2005

This study utilized pharmacokinetics/pharmacodynamics to compare b-lactam regimens for the empirical and definitive treatment of Gram-negative pulmonary infections in the ICU. Methods: Susceptibility data were extracted from the 2002 Intensive Care Unit Surveillance System (ISS) and pharmacokinetic parameters were obtained from published human studies. Monte Carlo simulation was used to model the free percent time above the MIC (free %T > MIC) for 18 b-lactam regimens against all Gram-negative isolates, Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter baumannii. The cumulative fraction of response (CFR) was determined for bacteriostatic and bactericidal targets (free %T > MIC): penicillins (‡30/50%), cephalosporins/monobactams (‡40/70%) and carbapenems (‡20/40%). Results: The 2002 ISS database contained MICs for 2408 Gram-negative isolates including 1430 Enterobacteriaceae, 799 P. aeruginosa, and 179 A. baumannii. Imipenem had the highest percentage susceptible for all Gram-negatives, Enterobacteriaceae and A. baumannii, while piperacillin/tazobactam had the highest percentage susceptible for P. aeruginosa. For empirical therapy, imipenem 0.5 g every 6 h, cefepime 2 g every 8 h and ceftazidime 2 g every 8 h demonstrated the highest CFR. For definitive therapy, imipenem 0.5 g every 6 h, ertapenem 1 g daily and cefepime 2 g every 8 h, cefepime 1 g every 8 h and cefepime 1 g every 12 h had the highest bactericidal CFR against Enterobacteriaceae; ceftazidime 2 g every 8 h, cefepime 2 g every 8 h, piperacillin/tazobactam 3.375 g every 4 h, ceftazidime 1 g every 8 h and aztreonam 1 g every 8 h against P. aeruginosa; and imipenem 0.5 g every 6 h, ticarcillin/clavulanate 3.1 g every 4 h, ceftazidime 2 g every 8 h, cefepime 2 g every 8 h and ticarcillin/clavulanate 3.1 g every 6 h against A. baumannii. Conclusions: Based on pharmacokinetics/pharmacodynamics, imipenem 0.5 g every 6 h, cefepime 2 g every 8 h and ceftazidime 2 g every 8 h should be the preferred b-lactam regimens for the empirical treatment of Gram-negative pulmonary infections in the ICU. The order of preference varied against Enterobacteriaceae, P. aeruginosa and A. baumannii.

Control of multi-resistant bacteria and ventilator-associated pneumonia: is it possible with changes in antibiotics?

Brazilian Journal of Infectious Diseases, 2007

Potent antimicrobial agents have been developed as a response to the development of antibiotic-resistant bacteria, which especially affect patients with prolonged hospitalization in Intensive Care Units (ICU) and who had been previously treated with antimicrobials, especially third-generation cephalosporins.This study was to determine how changes in the empirical treatment of infections in ICU patients affect the incidence of Gram-negative bacteria species and their susceptibility to antimicrobials, and examine the impact of these changes on nosocomial infections. A prospective interventional study was performed in a university hospital during two periods: 1) First period (September 1999 to February 2000); and 2) Second period (August 2000 to December 2000); empirical treatment was changed from ceftriaxone and/or ceftazidime in the first period to piperacillin/tazobactam in the second. ICU epidemiological and infection control rates, as well as bacterial isolates from upper airways were analyzed. Ceftazidime consumption dropped from 34.83 to 0.85 DDD/1000 patients per day (p=0.004). Piperacillin/tazobactam was originally not available; its consumption reached 157.07 DDD/1000 patients per day in the second period (p=0.0002). Eighty-seven patients and 66 patients were evaluated for upper airway colonization in the first and second periods, respectively. There was a significant decrease in the incidence of K. pneumoniae (p=0.004) and P. mirabilis (p=0.036), restoration of K. pneumoniae susceptibility to cephalosporins (p<0.0001) and reduction of ventilator-associated pneumonia rates (p<0.0001). However, there was an increase in P. aeruginosa incidence (p=0.005) and increases in ceftazidime (p=0.003) and meropenem (p<0.0001) susceptibilities. Changing antimicrobial selective pressure on multi-resistant Gram-negative bacteria helps control ventilator-associated pneumonia and decreases antimicrobial resistance.