piperacillin--tazobactam-drug-combination and Shock--Septic

Antibiotics may trigger alterations in mitochondrial function, which has been explored in cells culture, and in animal model of sepsis. This study sought to evaluate whether antibiotic therapy affects mitochondrial bioenergetics in a 68-patients clinical study. We studied mitochondrial respiratory rates at two time points: the first day of antibiotic administration and three days after. The Δbasal, ΔCI, ΔCII respiration, and ΔBCE respiratory rates were not different between patients administered with polymyxin, vancomycin, amoxicillin-clavulanate, and azithromycin compared to those who were not administered. Specific beta-lactams are associated with specific modifications in mitochondrial respiratory endpoints - patients who used meropenem had higher delta C2 values compared to those who did not (p = 0.03). Patients who used piperacillin-tazobactam had lower delta C1 (p = 0.03) values than those who did not, but higher delta C2 values (p = 0.02). These mitochondrial metabolic signatures in isolated lymphocytes challenges the proposed effects of antibiotics in mitochondrial bioenergetics of cell cultures, but at current status have an uncertain clinical significance.

Topics: Amoxicillin; Anti-Bacterial Agents; Azithromycin; beta-Lactams; Clavulanic Acid; Energy Metabolism; Humans; Lymphocytes; Meropenem; Mitochondria; Piperacillin, Tazobactam Drug Combination; Polymyxins; Prospective Studies; Shock, Septic; Vancomycin

To determine if aztreonam as initial empiric treatment of adult septic shock is associated with increased mortality compared to the use of anti-pseudomonal beta-lactam agents.. This was a multicenter, retrospective cohort study of 582 adult emergency department patients admitted to 12 acute care facilities within a single health system from January 2014 to December 2017 with septic shock receiving either aztreonam or an anti-pseudomonal beta-lactam for empiric treatment and discharged with an infection-related ICD-9 or ICD-10 code. The primary endpoint was in-hospital mortality.. Initial exposure to aztreonam was associated with increased hospital mortality compared to treatment with an anti-pseudomonal beta-lactam agent (22.7% vs. 12.9%, OR = 1.98, 95% CI: 1.27-3.11). When adjusted for APACHE II score, the treatment group effect on mortality remained statistically significant (OR = 1.74, 95% CI: 1.08-2.80). Aztreonam use was also associated with increased utilization of aminoglycosides (28.9% vs. 12.4%, p < 0.0001) and fluoroquinolones (50.5% vs. 25.8%, p < 0.01). There was no difference in hospital or intensive care unit length of stay in surviving patients between the two groups.. Compared to anti-pseudomonal beta-lactams, empiric treatment with aztreonam is associated with increased mortality and greater antibiotic exposure among patients with acute septic shock. These findings suggest that treatment with anti-pseudomonal beta-lactams should be prioritized over allergy avoidance whenever feasible.

Topics: Aged; Aged, 80 and over; Aminoglycosides; Anti-Bacterial Agents; APACHE; Aztreonam; beta-Lactams; Cefepime; Cohort Studies; Drug Hypersensitivity; Female; Fluoroquinolones; Hospital Mortality; Humans; Intensive Care Units; Length of Stay; Male; Meropenem; Middle Aged; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Risk Factors; Shock, Septic

Among patients with febrile neutropenia that developed after chemotherapy, high-risk patients, such as those having clinical instability or Multinational Association of Supportive Care in Cancer score of < 21, require hospitalization for intravenous empiric antibiotic therapy. Monotherapy with an anti-pseudomonal ß-lactam agent is recommended. Although many studies reported the microbial etiology of infections and resistant patterns of febrile neutropenia, the patients were not well characterized as having neutropenic septic shock. Therefore, this study aimed to determine the microbial spectrum of infections and resistance patterns of their isolates in patients with chemotherapy-induced neutropenic septic shock.. Data of adult patients diagnosed with neutropenic septic shock in the emergency department between June 2012 and December 2016 were extracted from a prospectively compiled septic shock registry at a single academic medical center. Thereafter, microbiological studies and antimicrobial susceptibility tests were conducted.. In total, 109 bacteria were found in patients with neutropenic septic shock. Gram-negative bacteria were the predominant causative organisms (84, 77.1%). Moreover, 33 microorganisms (30.3%) were multidrug-resistant (MDR) bacteria with extended-spectrum ß-lactamase-producing Escherichia coli (17, 50%) being the commonest. The most commonly affected sites in patients with MDR bacterial infections were the gastrointestinal tract (45%) and unknown (43.5%). Approximately 48.5% of MDR bacteria were resistant to cefepime but not to piperacillin-tazobactam or carbapenem.. MDR bacteria were prevalent in patients with chemotherapy-induced neutropenic septic shock. Therefore, piperacillin-tazobactam or carbapenem may be considered as empiric antibiotics if MDR bacteria are suspected to be causative agents.

Topics: Adult; Anti-Bacterial Agents; Drug Resistance, Bacterial; Humans; Neoplasms; Piperacillin, Tazobactam Drug Combination; Shock, Septic

The SEP-1 measures have tied financial reimbursement to the treatment of patients with severe sepsis and septic shock. The purpose of this study was to assess the impact of a SEP-1 initiative on the utilization of broad-spectrum combination therapy (BSCT) in the emergency department (ED).. This was an IRB-approved, retrospective evaluation of adult patients who received vancomycin plus an antipseudomonal beta-lactam for a urinary tract infection (UTI) or skin or soft tissue infection (SSTI) in the ED. The primary outcome was the proportion of patients in which use of BSCT was considered appropriate based on clinical criteria. Secondary outcomes included door to antibiotic order time, door to administration time, proportion of patients continued on BSCT upon admission, duration of BSCT, and in-hospital mortality.. A total of 400 patients were included in the analysis. Following SEP-1 implementation, appropriate use of BSCT decreased by 12%, with 54% of patients in the pre-SEP-1 group meeting clinical criteria compared to 42% in the post-SEP-1 group (p = 0.028). In the subgroup of patients with a suspected UTI the appropriate use of BSCT declined by 25% (40% vs 15%, p = 0.005). The median door to first antibiotic administration time was not significantly different between groups (63 min vs 61 min, p = 0.091).. The implementation of the SEP-1 mandated measures was associated with an increase in the unnecessary use of BSCT. Additionally, no difference was seen in time to antibiotic administration. The results of this study demonstrate the negative impact that the SEP-1 mandate may have on antimicrobial utilization within the ED.

Topics: Adult; Aged; Anti-Bacterial Agents; Aztreonam; beta-Lactams; Cefepime; Centers for Medicare and Medicaid Services, U.S.; Early Diagnosis; Early Medical Intervention; Emergency Service, Hospital; Female; Guideline Adherence; Hospital Mortality; Hospitalization; Humans; Male; Medical Overuse; Meropenem; Middle Aged; Patient Care Bundles; Piperacillin, Tazobactam Drug Combination; Reimbursement Mechanisms; Retrospective Studies; Sepsis; Shock, Septic; Soft Tissue Infections; Time-to-Treatment; United States; Urinary Tract Infections; Vancomycin

Gram-negative organisms (GNOs) have increasing resistance rates to levofloxacin at Virginia Commonwealth University Health System (VCUHS), where levofloxacin is the most common agent added to provide double coverage of gram-negative infections. The goal of this study was to determine the adequacy of empiric gram-negative coverage for septic patients at our institution.. A retrospective review of patients admitted to VCUHS, from January 1, 2014, to December 31, 2014, with a diagnosis of sepsis, severe sepsis, or septic shock and documented infection, was performed to determine the adequacy of various empiric antibiotic combinations.. Of 219 patients who met the inclusion criteria, 56% of patients received monotherapy and 21% of patients received combination therapy (2 antibiotics) covering GNOs. GNOs (84%) were susceptible to piperacillin-tazobactam. When used in combination with cefepime and meropenem, levofloxacin did not increase coverage. However, levofloxacin provided an 8% increase in coverage and gentamicin provided an additional 13% increase in coverage, respectively, when used in combination with piperacillin-tazobactam.. Among septic patients at VCUHS, gentamicin provided increased gram-negative coverage when compared with levofloxacin. Although susceptibility to piperacillin-tazobactam alone was relatively low, the combination of piperacillin-tazobactam and gentamicin provided nearly equivalent coverage to meropenem and gentamicin.

Topics: Academic Medical Centers; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Cefepime; Cephalosporins; Female; Gram-Negative Bacteria; Humans; Levofloxacin; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Sepsis; Shock, Septic; Virginia; Young Adult

To determine the frequency and cause of inadequate initial antibiotic therapy with vancomycin and piperacillin-tazobactam in patients with severe sepsis and septic shock in the emergency department (ED), characterize its impact on patient outcomes, and identify patients who would benefit from an alternative initial empiric regimen.. Retrospective cohort study conducted between 2012 and 2015 in which 342 patients with culture-positive severe sepsis or septic shock who received initial vancomycin and piperacillin-tazobactam were reviewed to determine appropriateness of antimicrobial therapy, risk factors for inappropriate use, and outcome data. Univariate and multivariate regression analyses were determined to identify associations between inappropriate antibiotic use and outcomes and to identify risk factors that may predict which patients would benefit from an alternative initial regimen.. Vancomycin and piperacillin-tazobactam were inappropriate for 24% of patients with severe sepsis or septic shock, largely due to non-susceptible infections, particularly ESBL organisms and Clostridium difficile. Risk factors included multiple sources of infection (OR 4.383), admission from a skilled nursing facility (OR 3.763), a history of chronic obstructive pulmonary disease (COPD) (OR 3.175), intra-abdominal infection (OR 2.890), and immunosuppression (OR 1.930). We did not find a mortality impact.. Vancomycin and piperacillin-tazobactam were an inappropriate antibiotic combination for approximately 24% of patients with either severe sepsis or septic shock in the ED. Patients with known COPD, residence at a skilled nursing facility, a history concerning for Clostridium difficile, and immunosuppression would benefit from an alternative regimen. Future prospective studies are needed to validate these findings.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; California; Drug Therapy, Combination; Emergency Service, Hospital; Female; Hospital Mortality; Humans; Inappropriate Prescribing; Male; Middle Aged; Multivariate Analysis; Piperacillin, Tazobactam Drug Combination; Regression Analysis; Retrospective Studies; Sepsis; Shock, Septic; Vancomycin

To determine if time to initial antimicrobial is associated with progression of severe sepsis to septic shock.. Retrospective cohort.. Six hundred fifty-six bed urban academic medical center.. Emergency department patients greater than or equal to 18 years old with severe sepsis and/or septic shock and antimicrobial administration within 24 hours. Patients with shock on presentation were excluded.. Not available.. We identified 3,929 severe sepsis patients, with overall mortality 12.8%. Nine hundred eighty-four patients (25.0%) progressed to septic shock. The median time to antimicrobial was 3.77 hours (interquartile range = 1.96-6.42) in those who progressed versus 2.76 hours (interquartile range = 1.60-4.82) in those who did not (p < 0.001). Multivariate logistic regression demonstrated that male sex (odds ratio = 1.18; 95% CI, 1.01-1.36), Charlson Comorbidity Index (odds ratio = 1.18; 95% CI, 1.11-1.27), number of infections (odds ratio = 1.05; 95% CI, 1.02-1.08), and time to first antimicrobial (odds ratio = 1.08; 95% CI, 1.06-1.10) were associated with progression. Each hour until initial antimicrobial administration was associated with a 8.0% increase in progression to septic shock. Additionally, time to broad-spectrum antimicrobial was associated with progression (odds ratio = 1.06; 95% CI, 1.05-1.08). Time to initial antimicrobial was also associated with in-hospital mortality (odds ratio = 1.05; 95% CI, 1.03-1.07).. This study emphasizes the importance of early, broad-spectrum antimicrobial administration in severe sepsis patients admitted through the emergency department, as longer time to initial antimicrobial administration is associated with increased progression of severe sepsis to septic shock and increased mortality.

Topics: Adult; Aged; Anti-Bacterial Agents; Ceftriaxone; Comorbidity; Disease Progression; Female; Hospital Mortality; Humans; Length of Stay; Levofloxacin; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Sepsis; Sex Factors; Shock, Septic; Time Factors; Time-to-Treatment; Vasoconstrictor Agents

Obesity and critical illness modify pharmacokinetics of antibiotics, but piperacillin-tazobactam continuous IV infusion pharmacokinetics has been poorly studied in obese critically ill patients. We aimed to compare pharmacokinetics of piperacillin in severely obese and nonobese patients with severe sepsis or septic shock. We hypothesized that plasma concentration variability would expose the critically ill to both piperacillin under and overdosing.. Prospective comparative study. Consecutive critically ill severely obese (body mass index, > 35 kg/m) and nonobese patients (body mass index, < 30 kg/m) were treated with 16 g/2 g/24 hr continuous piperacillin-tazobactam infusion. Piperacillin plasma concentration was measured every 12 hours over a 7-day period by high-pressure liquid chromatography. Unbound piperacillin plasma concentration and fractional time of plasma concentration spent over 64 mg/L (4-fold the minimal inhibitory concentration for Pseudomonas aeruginosa) were compared between the two groups. We performed 5,000 Monte Carlo simulations for various dosing regimens and minimal inhibitory concentration and calculated the probability to spend 100% of the time over 64 mg/L.. We enrolled 11 severely obese and 12 nonobese patients and obtained 294 blood samples. We did not observe a statistically significant difference in piperacillin plasma concentrations over time between groups. The fractional time over 64 mg/L was 64% (43-82%) and 93% (85-100%) in obese and nonobese patients, respectively, p = 0.027 with intra- and intergroup variability. Five nonobese and two obese patients experienced potentially toxic piperacillin plasma concentrations. When 64 mg/L was targeted, Monte Carlo simulations showed that 12 g/1.5 g/24 hr was inadequate in both groups and 16 g/2 g/24 hr was adequate only in nonobese patients.. Using a conventional dosing of 16 g/2 g/24 hr continuous infusion, obese patients were more likely than nonobese patients to experience piperacillin underdosing when facing high minimal inhibitory concentration pathogens. The present study suggests that piperacillin drug monitoring might be necessary in the sickest patients who are at the highest risk of unpredictable plasma concentration exposing them to overdose, toxicity, underdosing, and treatment failure.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Body Mass Index; Critical Illness; Dose-Response Relationship, Drug; Female; Humans; Infusions, Intravenous; Male; Microbial Sensitivity Tests; Middle Aged; Monte Carlo Method; Obesity; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Shock, Septic

The purpose of the study was to evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of piperacillin and tazobactam during high-volume haemodiafiltration (HVHDF).. A single dose of piperacillin/tazobactam (4/0.5 g) was administered as 30 minute infusion during HVHDF to 10 patients with acute kidney injury due to septic shock. Arterial blood samples were collected before and at 30 or 60 min intervals over 8 h (12 samples) after study drug administration. Concentrations of piperacillin and tazobactam were determined by HPLC-MS/MS. R software was used for population PK analysis and Monte Carlo Simulation of probability of PK/PD target attainment (PTA) in 1000 subjects.. A total of 101 samples were collected during HVHDF. The median (IQR) estimated glomerular filtration rate of the patients was 16 (11.25-27.5) ml/min/1.73 m(2) and HVHDF effluent rate was 208 (146.3-298.3) ml/kg/h. A final two-compartment population PK model predicted mean (%SE) total piperacillin clearance on HVHDF was 6.9 (6.4) l/h, volume of distribution of central compartment 9.0 (10.1) l and of peripheral compartment 11.2 (12.2) l. The PTA of 50% fT>MIC for piperacillin 4 g/tazobactam 0.5 g dosed every 8 h as 0.5-h and 4-h infusion was 84.3% and 100% for MIC of 16 mg/l respectively. Aiming 100% fT>MIC of 16 mg/l, the PTA values were 88.6% and 61.0%, for piperacillin 4 g/tazobactam 0.5 g 4-h infusion every 6 and 8 h respectively.. For bactericidal PK/PD target attainment piperacillin/tazobactam doses of 4/0.5 g every 8 h appear appropriate in septic shock patients with minimal residual renal function during HVHDF.

Topics: Aged; Anti-Bacterial Agents; beta-Lactamase Inhibitors; Female; Hemodiafiltration; Humans; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Shock, Septic

Sepsis is a potentially life-threatening condition that requires urgent management in an Emergency Department (ED). Evidence-based guidelines for managing sepsis have been developed; however, their integration into routine practice is often incomplete. Care maps may help clinicians meet guideline targets more often.. To determine if electronic clinical practice guidelines (eCPGs) improve management of patients with severe sepsis and septic shock (SS/SS).. The impact of an eCPG on the management of patients presenting with SS/SS over a 3-year period at a tertiary care ED was evaluated using retrospective case-control design and chart review methods. Cases and controls, matched by age and sex, were chosen from an electronic database using physician sepsis diagnoses. Data were compared using McNemar tests or paired t-tests, as appropriate.. Overall, 51 cases and controls were evaluated; the average age was 62 years, and 60% were male. eCPG patients were more likely to have a central venous pressure and central venous oxygen saturation measured; however, lactate measurement, blood cultures, and other investigations were similarly ordered (all p > 0.05). The administration of antibiotics within 3 h (63% vs. 41%; p = 0.03) and vasopressors (45% vs. 20%; p = 0.02) was more common in the eCPG group; however, use of corticosteroids and other interventions did not differ between the groups. Overall, survival was high and similar between groups.. A sepsis eCPG experienced variable use; however, physicians using the eCPG achieved more quality-of-care targets for SS/SS. Strategies to increase the utilization of eCPGs in Emergency Medicine seem warranted.

Topics: Aged; Anti-Bacterial Agents; Clinical Protocols; Disease Management; Emergency Service, Hospital; Female; Hospitals, Teaching; Humans; Internet; Male; Middle Aged; Penicillanic Acid; Pilot Projects; Piperacillin; Piperacillin, Tazobactam Drug Combination; Practice Guidelines as Topic; Sepsis; Shock, Septic; Treatment Outcome

Severe sepsis and septic shock can alter the pharmacokinetics of broad-spectrum β-lactams (meropenem, ceftazidime/cefepime, and piperacillin-tazobactam), resulting in inappropriate serum concentrations. Obesity may further modify the pharmacokinetics of these agents. We reviewed our data on critically ill obese patients (body mass index of ≥ 30 kg/m(2)) treated with a broad-spectrum β-lactam in whom therapeutic drug monitoring was performed and compared the data to those obtained in critically nonobese patients (body mass index of <25 kg/m(2)) to assess whether there were differences in reaching optimal drug concentrations for the treatment of nosocomial infections. Sixty-eight serum levels were obtained from 49 obese patients. There was considerable variability in β-lactam serum concentrations (coefficient of variation of 50% to 92% for the three drugs). Standard drug regimens of β-lactams resulted in insufficient serum concentrations in 32% of the patients and overdosed concentrations in 25%. Continuous renal replacement therapy was identified by multivariable analysis as a risk factor for overdosage and a protective factor for insufficient β-lactam serum concentrations. The serum drug levels from the obese cohort were well matched for age, gender, renal function, and sequential organ failure assessment (SOFA) score to 68 serum levels measured in 59 nonobese patients. The only difference observed between the two cohorts was in the subgroup of patients treated with meropenem and who were not receiving continuous renal replacement therapy: serum concentrations were lower in the obese cohort. No differences were observed in pharmacokinetic variables between the two groups. Routine therapeutic drug monitoring of β-lactams should be continued in obese critically ill patients.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; beta-Lactams; Case-Control Studies; Cefepime; Ceftazidime; Cephalosporins; Drug Monitoring; Enzyme Inhibitors; Female; Humans; Male; Meropenem; Middle Aged; Obesity; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Renal Replacement Therapy; Sepsis; Shock, Septic; Tazobactam; Thienamycins; Young Adult

Raoultella planticola (formerly Klebsiella planticola) is a Gram-negative bacterium that has been rarely reported in association with human infection. Here we describe a case of cholangitis complicated with septic shock caused by R. planticola in an immunocompromised patient with advanced cancer who underwent endoscopic retrograde cholangiopancreatography to extract common bile duct stones. The infection was cleared by piperacillin-tazobactam treatment.

Topics: Aged; Anti-Bacterial Agents; Cholangitis; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Immunocompromised Host; Male; Neoplasms; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Shock, Septic; Treatment Outcome

Sepsis is responsible for important alterations in the pharmacokinetics of antibiotics. Continuous renal replacement therapy (CRRT), which is commonly used in septic patients, may further contribute to pharmacokinetic changes. Current recommendations for antibiotic doses during CRRT combine data obtained from heterogeneous patient populations in which different CRRT devices and techniques have been used. We studied whether these recommendations met optimal pharmacokinetic criteria for broad-spectrum antibiotic levels in septic shock patients undergoing CRRT.. This open, prospective study enrolled consecutive patients treated with CRRT and receiving either meropenem (MEM), piperacillin-tazobactam (TZP), cefepime (FEP) or ceftazidime (CAZ). Serum concentrations of these antibiotics were determined by high-performance liquid chromatography from samples taken before (t = 0) and 1, 2, 5, and 6 or 12 hours (depending on the β-lactam regimen) after the administration of each antibiotic. Series of measurements were separated into those taken during the early phase (< 48 hours from the first dose) of therapy and those taken later (> 48 hours).. A total of 69 series of serum samples were obtained in 53 patients (MEM, n = 17; TZP, n = 16; FEP, n = 8; CAZ, n = 12). Serum concentrations remained above four times the minimal inhibitory concentration for Pseudomonas spp. for the recommended time in 81% of patients treated with MEM, in 71% with TZP, in 53% with CAZ and in 0% with FEP. Accumulation after 48 hours of treatment was significant only for MEM.. In septic patients receiving CRRT, recommended doses of β-lactams for Pseudomonas aeruginosa are adequate for MEM but not for TZP, FEP and CAZ; for these latter drugs, higher doses and/or extended infusions should be used to optimise serum concentrations.

Topics: Aged; Anti-Bacterial Agents; beta-Lactams; Cefepime; Ceftazidime; Cephalosporins; Dose-Response Relationship, Drug; Female; Humans; Intensive Care Units; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Practice Guidelines as Topic; Prospective Studies; Pseudomonas aeruginosa; Renal Replacement Therapy; Shock, Septic; Thienamycins

The optimal approach for empirical antibiotic therapy in patients with severe sepsis and septic shock remains controversial. A retrospective cohort study was conducted in the intensive care units of a university hospital. The data from 760 patients with severe sepsis or septic shock associated with Gram-negative bacteremia was analyzed. Among this cohort, 238 (31.3%) patients received inappropriate initial antimicrobial therapy (IIAT). The hospital mortality rate was statistically greater among patients receiving IIAT compared to those initially treated with an appropriate antibiotic regimen (51.7% versus 36.4%; P < 0.001). Patients treated with an empirical combination antibiotic regimen directed against Gram-negative bacteria (i.e., beta-lactam plus aminoglycoside or fluoroquinolone) were less likely to receive IIAT compared to monotherapy (22.2% versus 36.0%; P < 0.001). The addition of an aminoglycoside to a carbapenem would have increased appropriate initial therapy from 89.7 to 94.2%. Similarly, the addition of an aminoglycoside would have increased the appropriate initial therapy for cefepime (83.4 to 89.9%) and piperacillin-tazobactam (79.6 to 91.4%). Logistic regression analysis identified IIAT (adjusted odds ratio [AOR], 2.30; 95% confidence interval [CI] = 1.89 to 2.80) and increasing Apache II scores (1-point increments) (AOR, 1.11; 95% CI = 1.09 to 1.13) as independent predictors for hospital mortality. In conclusion, combination empirical antimicrobial therapy directed against Gram-negative bacteria was associated with greater initial appropriate therapy compared to monotherapy in patients with severe sepsis and septic shock. Our experience suggests that aminoglycosides offer broader coverage than fluoroquinolones as combination agents for patients with this serious infection.

Topics: Acinetobacter Infections; Adult; Aged; Aminoglycosides; Anti-Bacterial Agents; Carbapenems; Cefepime; Cephalosporins; Cohort Studies; Drug Therapy, Combination; Escherichia coli Infections; Female; Fluoroquinolones; Gram-Negative Bacterial Infections; Hospital Mortality; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Sepsis; Shock, Septic