piperacillin--tazobactam-drug-combination and Gram-Negative-Bacterial-Infections

Roseomonas mucosa, as a Gram-negative coccobacilli, is an opportunistic pathogen that has rarely been reported in human infections. Here we describe a case of bacteremia in an infective endocarditis patient with systemic lupus erythematosus (SLE).. A 44-year-old female patient with SLE suffered bacteremia caused by Roseomonas mucosa complicated with infective endocarditis (IE). The patient started on treatment with piperacillin-tazobactam and levofloxacin against Roseomonas mucosa, which was switched after 4 days to meropenem and amikacin for an additional 2 weeks. She had a favorable outcome with a 6-week course of intravenous antibiotic therapy.. Roseomonas mucosa is rarely reported in IE patients; therefore, we report the case in order to improve our ability to identify this pathogen and expand the range of known bacterial causes of infective endocarditis.

Topics: Adult; Amikacin; Anti-Bacterial Agents; Bacteremia; Endocarditis; Endocarditis, Bacterial; Female; Gram-Negative Bacterial Infections; Humans; Levofloxacin; Lupus Erythematosus, Systemic; Methylobacteriaceae; Piperacillin, Tazobactam Drug Combination

Bordetella trematum is an infrequent Gram-negative coccobacillus, with a reservoir, pathogenesis, a life cycle and a virulence level which has been poorly elucidated and understood. Related information is scarce due to the low frequency of isolates, so it is important to add data to the literature about this microorganism.. We report a case of a 74-year-old female, who was referred to the hospital, presenting with ulcer and necrosis in both legs. Therapy with piperacillin-tazobactam was started and peripheral artery revascularization was performed. During the surgery, a tissue fragment was collected, where Bordetella trematum, Stenotrophomonas maltophilia, and Enterococcus faecalis were isolated. After surgery, the intubated patient was transferred to the intensive care unit (ICU), using vasoactive drugs through a central venous catheter. Piperacillin-tazobactam was replaced by meropenem, with vancomycin prescribed for 14 days. Four days later, levofloxacin was added for 24 days, aiming at the isolation of S. maltophilia from the ulcer tissue. The necrotic ulcers evolved without further complications, and the patient's clinical condition improved, leading to temporary withdrawal of vasoactive drugs and extubation. Ultimately, however, the patient's general condition worsened, and she died 58 days after hospital admission.. Despite being a rare finding, B. trematum is typically associated with the clinical manifestation of disorders that predispose to ulcer development, which can be infected by microorganisms. The combination of antibiotic therapy and surgical debridement plays a key role in preventing systemic infections. Monitoring the appearance of new cases of B. trematum is essential, since it can be an emerging microorganism. Isolating and defining the clinical relevance of unusual bacteria yields a more accurate perspective in the development of new diagnostic tools and allows for assessment of proper antimicrobial therapy.

Topics: Aged; Anti-Bacterial Agents; Bordetella; Bordetella Infections; Coinfection; Diabetic Foot; Enterococcus faecalis; Fatal Outcome; Female; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Intensive Care Units; Microbial Sensitivity Tests; Necrosis; Piperacillin, Tazobactam Drug Combination; Stenotrophomonas maltophilia; Ulcer

INTRODUCTIONBeta-lactam/beta-lactamase inhibitor combination antimicrobials (BLBLIs) are among the most controversial classes of antibiotic agents available for the treatment of infections caused by extended-spectrum-beta-lactamase (ESBL)-producing Gram-negative bacteria (ESBL-GNR). Piperacillin-tazobactam (PTZ) is one of the most frequently utilized antibiotic agents for empirical Gram-negative bacterial coverage and remains active against a large proportion of ESBL-GNR strains. Furthermore, good antimicrobial stewardship practices encourage the use of carbapenem-sparing treatment regimens for infections due to ESBL-GNR. As rapid diagnostics are increasingly used in the clinical microbiology laboratory and have the capability of detecting CTX-M type or other ESBL resistance mechanisms, this issue continues to be pertinent. Some data imply reduced efficacy of PTZ against ESBLs. Several factors may affect a clinician's choice to use BLBLIs, including the isolate's MIC, the site and severity of infection, and the type of resistance mechanism. These factors are explored in this review of the pros and cons of BLBLI treatment of invasive infections due to ESBL-producing bacteria, as well as how laboratories should report results for BLBLIs for these organisms as they relate to antimicrobial stewardship. In this Point-Counterpoint, Audrey Schuetz provides the pro point of view and Sergio Reyes and Pranita Tamma provide the con, counterpoint view.

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamase Inhibitors; Carbapenems; Clinical Decision-Making; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Microbial Sensitivity Tests; Piperacillin, Tazobactam Drug Combination

Extended spectrum β-lactamases (ESBL) and AmpC β-lactamases are increasing causes of resistance in many Gram-negative pathogens of common infections. This has led to a growing utilization of broad spectrum antibiotics, most predominately the carbapenem agents. As the prevalence of ESBL and AmpC-producing isolates and carbapenem resistance has increased, interest in effective alternatives for the management of these infections has also developed.. This article summarizes clinical literature evaluating the utility of carbapenem-sparing regimens for the treatment of ESBL and AmpC-producing Enterobacteriaceae, mainly β-lactam-β-lactamase inhibitor combinations and cefepime (FEP).. Based on available data, the use of piperacillin-tazobactam (PTZ) and FEP in the treatment of ESBL-producing Enterobacteriaceae cannot be widely recommended. However, certain infections and patient characteristics may support for effective use of these alternative agents. In the treatment of infections caused by AmpC-producing Enterobacteriaceae, FEP has been shown to be a clinically useful carbapenem-sparing alternative. Carbapenems and FEP share many structurally similar characteristics in regards to susceptibility to AmpC β-lactamases, which further create confidence in the use FEP in these situations. Patient and infection specific characteristics should be used to employ FEP optimally.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamase Inhibitors; beta-Lactamases; beta-Lactams; Cefepime; Cephalosporins; Drug Resistance, Bacterial; Drug Therapy, Combination; Enterobacteriaceae; Enterobacteriaceae Infections; Gram-Negative Aerobic Bacteria; Gram-Negative Bacterial Infections; Humans; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination

Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic disorder resulting from ovulation induction. Although the occurrence of this disorder is rare, it can be potentially life-threatening in its most severe forms. We herein present the case of a young nulliparous woman who presented with features of abdominal compartment syndrome and was subsequently diagnosed with severe OHSS. All physicians, in particular critical care doctors, must be aware of this rare, but potentially life-threatening iatrogenic disorder.

Topics: Adult; Anti-Bacterial Agents; Ceftazidime; Female; Gram-Negative Bacterial Infections; Humans; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Penicillanic Acid; Peritonitis; Piperacillin; Piperacillin, Tazobactam Drug Combination; Stenotrophomonas maltophilia; Treatment Outcome

Rahnella aquatilis infections are rare. We report the case of a 46-y-old African-American male with relapsed acute lymphoblastic leukemia who had R. aquatilis bacteremia after beginning reinduction chemotherapy. He was treated for 4 weeks with piperacillin-tazobactam and gentamicin. He recovered from the infection and had an allogenic bone marrow transplant a month later.

Topics: Bacteremia; Bone Marrow Transplantation; Burkitt Lymphoma; Drug Therapy, Combination; Gram-Negative Bacterial Infections; Humans; Immunocompromised Host; Immunosuppressive Agents; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Rahnella

Extended infusion of piperacillin/tazobactam over 4 h has been proposed as an alternate mode of administration to the 30-min intermittent infusion to optimize treatment effects in patients with gram-negative bacterial infections. The study aimed to evaluate the extended infusion regimen of piperacillin/tazobactam in standings of efficacy, safety, and cost to the intermittent one in the treatment of gram-negative bacterial infections. A prospective randomized comparative study was performed on 53 patients, 27 in the intermittent infusion group and 26 in the extended infusion group. The primary outcome was the mean number of days to clinical success and the percentage of patients who were clinically cured after treatment. The secondary outcomes included mortality, readmission within 30-days, and cost-effectiveness analysis based on the mean number of days to clinical success. The clinical success rate was comparable in the two groups. Days on extended infusion were significantly lower than intermittent infusion (5.7 vs 8.9 days, respectively, p = 0.0001) as well as days to clinical success (4.6 vs 8.5 days, respectively, p = 0.026). The extended infusion was superior to the intermittent infusion regarding cost-effectiveness ratio ($1835.41 and $1914.09/expected success, respectively). The more cost-effective regimen was the extended infusion. Both regimens had comparable clinical and microbiological outcomes.

Topics: Anti-Bacterial Agents; Cost-Benefit Analysis; Critical Illness; Egypt; Gram-Negative Bacterial Infections; Humans; Infusions, Intravenous; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies

Cefepime/enmetazobactam is a novel β-lactam/β-lactamase inhibitor combination and a potential empirical therapy for resistant gram-negative infections.. To evaluate whether cefepime/enmetazobactam was noninferior to piperacillin/tazobactam for the primary outcome of treatment efficacy in patients with complicated urinary tract infections (UTIs) or acute pyelonephritis.. A phase 3, randomized, double-blind, active-controlled, multicenter, noninferiority clinical trial conducted at 90 sites in Europe, North and Central America, South America, and South Africa. Recruitment occurred between September 24, 2018, and November 2, 2019. Final follow-up occurred November 26, 2019. Participants were adult patients aged 18 years or older with a clinical diagnosis of complicated UTI or acute pyelonephritis caused by gram-negative urinary pathogens.. Eligible patients were randomized to receive either cefepime, 2 g/enmetazobactam, 0.5 g (n = 520), or piperacillin, 4 g/tazobactam, 0.5 g (n = 521), by 2-hour infusion every 8 hours for 7 days (up to 14 days in patients with a positive blood culture at baseline).. The primary outcome was the proportion of patients in the primary analysis set (patients who received any amount of study drug with a baseline gram-negative pathogen not resistant to either treatment and ≥105 colony-forming units [CFU]/mL in urine culture or the same pathogen present in concurrent blood and urine cultures) who achieved overall treatment success (defined as clinical cure combined with microbiological eradication [<103 CFU/mL in urine] of infection). Two-sided 95% CIs were computed using the stratified Newcombe method. The prespecified noninferiority margin was -10%. If noninferiority was established, a superiority comparison was also prespecified.. Among 1041 patients randomized (mean age, 54.7 years; 573 women [55.0%]), 1034 (99.3%) received study drug and 995 (95.6%) completed the trial. Among the primary analysis set, the primary outcome occurred in 79.1% (273/345) of patients receiving cefepime/enmetazobactam compared with 58.9% (196/333) receiving piperacillin/tazobactam (between-group difference, 21.2% [95% CI, 14.3% to 27.9%]). Treatment-emergent adverse events occurred in 50.0% (258/516) of patients treated with cefepime/enmetazobactam and 44.0% (228/518) with piperacillin/tazobactam; most were mild to moderate in severity (89.9% vs 88.6%, respectively). A total of 1.7% (9/516) of participants who received cefepime/enmetazobactam and 0.8% (4/518) of those who received piperacillin/tazobactam did not complete the assigned therapy due to adverse events.. Among patients with complicated UTI or acute pyelonephritis caused by gram-negative pathogens, cefepime/enmetazobactam, compared with piperacillin/tazobactam, met criteria for noninferiority as well as superiority with respect to the primary outcome of clinical cure and microbiological eradication. Further research is needed to determine the potential role for cefepime/enmetazobactam in the treatment of complicated UTI and pyelonephritis.. ClinicalTrials.gov Identifier: NCT03687255.

Topics: Acute Disease; Anti-Bacterial Agents; beta-Lactamase Inhibitors; Cefepime; Double-Blind Method; Drug Combinations; Female; Gram-Negative Bacterial Infections; Humans; Infusions, Intravenous; Male; Middle Aged; Piperacillin, Tazobactam Drug Combination; Pyelonephritis; Urinary Tract Infections

Timely administration of appropriate empirical antibiotics in febrile neutropenia is crucial for favourable patient outcomes. There are guidelines in place recommending such antibiotics. However, regional variations and local epidemiological data must be evaluated to tailor the antibiotics for best possible and rational use. In this study, we audited the clinical and microbiological data of febrile neutropenic episodes occurring at a tertiary care haematology institution. Three hundred and ninety-three febrile neutropenic episodes occurring in 123 patients over a 1-year period were analysed for microbial profile, sensitivity and resistance patterns, and finally clinical outcomes. Gram-negative bacilli (GNB) blood stream infections (46.9%) were more prevalent as compared to gram-positive infections (41.9%). Overall mortality due to complicated neutropenic sepsis was 19.5% (24/123 patients). Increased resistance to carbapenems, beta-lactam beta-lactamase inhibitor combinations, aminoglycosides, fluoroquinolones, and cephalosporins were observed. Cefepime and tigecycline resistance were seen in 20% and 15% GNB isolates, respectively. Chest was the most frequent focus of infection, and acute myeloid leukaemia (AML) was the most common underlying disorder which correlated with the likelihood of death (p < 0.01). Multidrug-resistant GNB (esp. Klebsiella sp.) are still most worrisome isolates in neutropenic patients. Single-agent cefepime or piperacillin-tazobactam/tigecycline combination may be considered empirical agents. Chest infections and AML were independent predictors of poor clinical outcome in neutropenic patients. Regular audit of infections and antibiotic susceptibility data is needed to improve clinical outcomes in patients with febrile neutropenia.

Topics: Adolescent; Adult; Cefepime; Drug Resistance, Multiple, Bacterial; Febrile Neutropenia; Female; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; India; Leukemia, Myeloid, Acute; Male; Middle Aged; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Tigecycline

ß-Lactam antibiotics demonstrate time-dependent killing. Prolonged infusion of these agents is commonly performed to optimize the time the unbound concentration of an antibiotic remains greater than the minimum inhibitory concentration and decrease costs, despite limited evidence suggesting improved clinical results.. To determine whether prolonged infusion of ß-lactam antibiotics improves outcomes in critically ill patients with suspected gram-negative infection.. We conducted a single-center, before-after, comparative effectiveness trial between January 2010 and January 2011 in the intensive care units at Barnes-Jewish Hospital, an urban teaching hospital affiliated with the Washington University School of Medicine in St. Louis, MO. Outcomes were compared between patients who received standardized dosing of meropenem, piperacillin-tazobactam, or cefepime as an intermittent infusion over 30 minutes (January 1, 2010, to June 30, 2010) and patients who received prolonged infusion over 3 hours (August 1, 2010, to January 31, 2011).. A total of 503 patients (intermittent infusion, n = 242; prolonged infusion, n = 261) treated for gram-negative infection were included in the clinically evaluable population. Approximately 50% of patients in each group received cefepime and 20% received piperacillin-tazobactam. More patients in the intermittent infusion group received meropenem (35.5% vs 24.5%; p = 0.007). Baseline characteristics were similar between groups, with the exception of a greater occurrence of chronic obstructive pulmonary disease (COPD) in the intermittent infusion group. Treatment success rates in the clinically evaluable group were 56.6% for intermittent infusion and 51.0% for prolonged infusion (p = 0.204), and in the microbiologically evaluable population, 55.2% for intermittent infusion and 49.5% for prolonged infusion (p = 0.486). Fourteen-day, 30-day, and inhospital mortality rates in the clinically evaluable population for the intermittent and prolonged infusion groups were 13.2% versus 18.0% (p = 0.141), 23.6% versus 25.7% (p = 0.582), and 19.4% versus 23.0% (p = 0.329).. Routine use of prolonged infusion of time-dependent antibiotics for the empiric treatment of gram-negative bacterial infections offers no advantage over intermittent infusion antibiotic therapy with regard to treatment success, mortality, or hospital length of stay. These results were confirmed after controlling for potential confounders in a multivariate analysis.

Topics: Aged; Anti-Bacterial Agents; beta-Lactams; Cefepime; Cephalosporins; Cohort Studies; Cross Infection; Drug Administration Schedule; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Hospitals, Teaching; Hospitals, Urban; Humans; Infusions, Intravenous; Intensive Care Units; Length of Stay; Male; Meropenem; Middle Aged; Missouri; Penicillanic Acid; Pilot Projects; Piperacillin; Piperacillin, Tazobactam Drug Combination; Thienamycins

Our unit adopted the single administration of cefepime as the initial treatment for febrile episodes in neutropenic patients with hematological malignancies. However, recently, cefepime-resistant gram-negative bacteremia, including those with extended-spectrum β-lactamase (ESBL)-producers, was frequently observed in these patients. Therefore, we instituted a rotation of primary antibiotics for febrile neutropenic patients in an attempt to control antibiotic resistance.. This prospective trial was performed from August 2008 through March 2011 at our unit. After a pre-intervention period, in which cefepime was used as the initial agent for febrile neutropenia, 4 primary antibiotics, namely, piperacillin-tazobactam, ciprofloxacin, meropenem, and cefepime, were rotated at 1-month intervals over 20 months. Blood and surveillance cultures were conducted for febrile episodes, in order to assess the etiology, the resistance pattern (particularly to cefepime), and the prognosis.. In this trial, 219 patients were registered. A 65.9% reduction in the use of cefepime occurred after the antibiotic rotation. In the surveillance stool cultures, the detection rate of cefepime-resistant gram-negative isolates, of which ESBL-producers were predominant, declined significantly after the intervention (8.5 vs 0.9 episodes per 1000 patient days before and after intervention respectively, P<0.01). Interestingly, ESBL-related bacteremia was not detected after the initiation of the trial (1.7 vs 0.0 episodes per 1000 patient days before and after intervention respectively, P<0.01). Infection-related mortality was comparable between the 2 periods.. We implemented a monthly rotation of primary antibiotics for febrile neutropenic patients. An antibiotic heterogeneity strategy, mainly performed as a cycling regimen, would be useful for controlling antimicrobial resistance among patients treated for febrile neutropenia.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; beta-Lactam Resistance; Cefepime; Cephalosporins; Ciprofloxacin; Drug Administration Schedule; Female; Fever; Gram-Negative Bacterial Infections; Hematologic Neoplasms; Humans; Male; Meropenem; Middle Aged; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Thienamycins

To compare the safety and efficacy of sequential intravenous (IV) to oral (PO) moxifloxacin treatment against a standard antimicrobial regimen of IV piperacillin-tazobactam followed by PO amoxicillin-clavulanate for the treatment of adults with complicated intra-abdominal infection (cIAI).. cIAIs are commonly due to mixed aerobic and anaerobic bacteria and require both source control and broad-spectrum antibiotic therapy.. A prospective, double-blind, randomized, phase III comparative trial. Patients with cIAI were stratified by disease severity (APACHE II score) and randomized to either IV/PO moxifloxacin (400 mg q24 hours) or comparator (IV piperacillin-tazobactam [3.0/0.375 g q6 hours] +/- PO amoxicillin-clavulanate [800 mg/114 mg q12 hours]), each for 5 to 14 days. The primary efficacy variable was clinical cure rate at the test-of-cure visit (days 25-50). Bacteriologic outcomes were also determined.. : Of 656 intent-to-treat patients, 379 (58%) were valid to assess efficacy (183 moxifloxacin, 196 comparator). Demographic and baseline medical characteristics were similar between the 2 groups. Clinical cure rates at test-of-cure were 80% (146 of 183) for moxifloxacin versus 78% (153 of 196) for comparator (95% confidence interval, -7.4%, 9.3%). The clinical cure rate at test-of-cure for hospital-acquired cIAI was higher with moxifloxacin (82%, 22 of 27) versus comparator (55%, 17 of 31; P = 0.05); rates were similar for community-acquired infections (80% [124 of 156] versus 82% [136 of 165], respectively). Bacterial eradication rates were 78% (117 of 150) with moxifloxacin versus 77% (126 of 163) in the comparator group (95% confidence interval, -9.9%, 8.7%).. Once daily IV/PO moxifloxacin monotherapy was as least as effective as standard IV piperacillin-tazobactam/PO amoxicillin-clavulanate dosed multiple times daily for the treatment of cIAIs.

Topics: Abdominal Abscess; Administration, Oral; Adult; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Appendicitis; Aza Compounds; Bacterial Infections; Cross Infection; Double-Blind Method; Female; Fluoroquinolones; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Injections, Intravenous; Intestinal Perforation; Male; Middle Aged; Moxifloxacin; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Quinolines; Safety; Stomach Rupture; Treatment Outcome

The selection of resistant gram-negative bacilli by broad-spectrum antibiotic use is a major issue in infection control. The aim of this comparative study was to assess the impact of different antimicrobial regimens commonly used to treat intra-abdominal infections on the susceptibility patterns of gram-negative bowel flora after completion of therapy. In two international randomized open-label trials with laboratory blinding, adults with complicated intra-abdominal infection requiring surgery received piperacillin-tazobactam (OASIS 1) or ceftriaxone/metronidazole (OASIS II) versus ertapenem for 4-14 days. Rectal swabs were obtained at baseline, end of therapy, and 2 weeks post-therapy. Escherichia coli and Klebsiella spp. were tested for production of extended-spectrum beta-lactamase (ESBL). Enterobacteriaceae resistant to the agent used were recovered from 19 of 156 (12.2%) piperacillin-tazobactam recipients at the end of therapy compared to 1 (0.6%) patient at baseline (p<0.001) in OASIS I, and from 33 of 193 (17.1%) ceftriaxone/metronidazole recipients at the end of therapy compared to 5 (2.6%) patients at baseline (p<0.001) in OASIS II. Ertapenem-resistant Enterobacteriaceae were recovered from 1 of 155 and 1 of 196 ertapenem recipients at the end of therapy versus 0 and 1 ertapenem recipients at baseline in OASIS I and II, respectively. Resistant Enterobacteriaceae emerged significantly less often during treatment with ertapenem than with the comparator in both OASIS I (p<0.001) and OASIS II (p<0.001). The prevalence of ESBL-producers increased significantly during therapy in OASIS II among 193 ceftriaxone/metronidazole recipients (from 4 [2.1%] to 18 [9.3%]) (p<0.001), whereas no ertapenem recipient was colonized with an ESBL-producer at the end of therapy in either study. Selection for imipenem-resistant Pseudomonas aeruginosa was uncommon in all treatment groups. In these studies, the frequency of bowel colonization with resistant Enterobacteriaceae substantially increased in patients treated with either piperacillin-tazobactam or ceftriaxone/metronidazole, but not in patients treated with ertapenem.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactams; Carrier State; Ceftriaxone; Digestive System Surgical Procedures; Drug Resistance, Bacterial; Drug Therapy, Combination; Ertapenem; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Intestines; Lactams; Male; Metronidazole; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination

Although perioperative antibiotic prophylaxis has significantly reduced surgical wound infection rates, this complication is still a frequent complication of head and neck cancer surgery. Because these infections are typically polymicrobial, our study evaluated the safety and efficacy of piperacillin-tazobactam in the treatment of surgical wound infection after clean-contaminated head and neck oncologic surgery.. In this multicenter, prospective clinical trial, 70 patients with surgical wound infection received piperacillin-tazobactam.. Of patients who were evaluable, 92.4% were also clinically cured or improved, and the bacteriologic eradication rate was 80.3%. Of the 70 patients enrolled in the study, six (8.5%) experienced six adverse events: two cases of moderate diarrhea, one allergic skin reaction, and three cases of phlebitis. No deaths were attributable to the study drug.. Piperacillin-tazobactam is a good choice of treatment as monotherapy for surgical wound infection after clean-contaminated head and neck oncologic surgery.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Female; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Head and Neck Neoplasms; Humans; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Surgical Wound Infection; Treatment Outcome

To examine the clinical efficacy and safety of ertapenem, a novel beta-lactam agent with wide activity against common pathogens encountered in intraabdominal infection.. Ertapenem has a pharmacokinetic profile and antimicrobial spectrum that support the potential for use as a once-a-day agent for the treatment of common mixed aerobic and anaerobic infections. METHODS This prospective, randomized, controlled, and double-blind trial was conducted to compare the safety and efficacy of ertapenem with piperacillin/tazobactam as therapy following adequate surgical management of complicated intraabdominal infections.. Six hundred thirty-three patients were included in the modified intent-to-treat population, with 396 meeting all criteria for the evaluable population. Patients with a wide range of infections were enrolled; perforated or abscessed appendicitis was most common (approximately 60% in microbiologically evaluable population). A prospective, expert panel review was conducted to assess the adequacy of surgical source control in patients who were failures as a component of evaluability. For the modified intent-to-treat groups, 245 of 311 patients treated with ertapenem (79.3%) were cured, as were 232 of 304 (76.2) treated with piperacillin/tazobactam. One hundred seventy-six of 203 microbiologically evaluable patients treated with ertapenem (86.7%) were cured, as were 157 of the 193 (81.2%) treated with piperacillin/tazobactam.. In this study, the efficacy of ertapenem 1 g once a day was equivalent to piperacillin/tazobactam 3.375 g every 6 hours in the treatment of a range of intraabdominal infections. Ertapenem was generally well tolerated and had a similar safety and tolerability profile to piperacillin/tazobactam. A formal process for review of adequacy of source control was found to be of benefit. The results of this trial suggest that ertapenem may be a useful option that could eliminate the need for combination and/or multidosed antibiotic regimens for the empiric treatment of intraabdominal infections.

Topics: Abdominal Abscess; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactams; Digestive System Surgical Procedures; Double-Blind Method; Drug Therapy, Combination; Ertapenem; Female; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Hospitalization; Humans; Lactams; Male; Middle Aged; Penicillanic Acid; Peritonitis; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Research Design; Treatment Outcome

The aim of this study was to determine the clinical and bacteriological efficacy and safety of piperacillin-tazobactam (PT) (4g/500 mg IV tid) in the treatment of 107 adult patients with lower respiratory tract infections (LRTI) requiring hospitalization. Patients included were 66 men and 41 women with a mean age of 55.2 years (range 18-89), enrolled from Mexican (6) and Argentinean (5) hospitals. Ninety-nine clinically evaluable patients (92.5%), 87 with pneumonia and 12 with bronchitis, were treated for a mean period of 9.3 and 7.3 days, respectively. Response to treatment was favorable in 94.3% cases with pneumonia and 100% of cases with bronchitis; 86 cases (80.3%) were bacteriologically evaluable, 77 with pneumonia (eradication 74, persistence 1, superinfection 2), and 9 with bronchitis (eradication in all). Streptococcus pneumoniae was recovered in 24, Klebsiella pneumoniae in 21, Staphylococcus aureus in 8, Haemophilus influenzae in 7, Pseudomonas aeruginosa in 5, Enterobacter spp. in 6, Escherichia coli in 6 and other organisms in 12. Toxicity or intolerance were not observed. Our data suggest that PT is a reliable therapy for severe LRTI.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Drug Administration Schedule; Drug Therapy, Combination; Female; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Respiratory Tract Infections

In the treatment of septic patients, the prediction of a pathogen's susceptibility to piperacillin

Topics: Anti-Bacterial Agents; Escherichia coli; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Klebsiella pneumoniae; Microbial Sensitivity Tests; Piperacillin, Tazobactam Drug Combination; Pseudomonas aeruginosa; Reproducibility of Results; Sepsis

Chromobacterium violaceum is a motile gram-negative bacterium. This bacterium commonly grows in tropical or subtropical areas in sewage and can cause opportunistic infections.. A 50-year-old Chinese man had a skin ulcer in the middle of his left leg in front of the tibia. The diameter of the wound was 3.0 cm, the exudation was obvious, and necrotic tissue was attached to the wound. One week previously, he was working in a field where he accidentally punctured his left leg.. C violaceum infection was diagnosed as per the results of pathogen culture from the infection site.. He was treated with piperacillin/tazobactam (3.375 g/12 h iv) and levofloxacin (0.5 g/24 h iv) for 5 days.. The patient showed good response to therapy and was discharged on day 18 after wound healing.. C violaceum rarely infects humans. When an infection is suspected, samples should be immediately sent for microbial culture. Timely treatment on the basis of drug sensitivity test results can prevent further complications.

Topics: Administration, Intravenous; Chromobacterium; Drug Therapy, Combination; Gram-Negative Bacterial Infections; Humans; Levofloxacin; Lower Extremity; Male; Middle Aged; Opportunistic Infections; Piperacillin, Tazobactam Drug Combination; Skin; Skin Ulcer; Treatment Outcome

Piperacillin/tazobactam has long been a broad-spectrum 'workhorse' antibiotic; however, it is compromised by resistance. One response is to re-partner tazobactam with cefepime, which is easier to protect, being less β-lactamase labile, and to use a high-dose and prolonged infusion. On this basis, Wockhardt are developing cefepime/tazobactam (WCK 4282) as a 2+2 g q8h combination with a 90-min infusion.. The activity of cc cefepime/tazobactam was assessed, with other tazobactam combinations as comparators, against 1632 Enterobacterales, 745 Pseudomonas aeruginosa and 450 other non-fermenters, as submitted to the UK National Reference Laboratory. These were categorised by carbapenemase-gene detection and interpretive reading of phenotypes, with MICs determined by British Society for Antimicrobial Chemotherapy agar dilution.. Although higher breakpoints may be justifiable, based on the pharmacodynamics, the results were reviewed against current cefepime criteria. On this basis, cefepime/tazobactam was broadly active against Enterobacterales with AmpC enzymes and extended-spectrum β-lactamases (ESBLs), even when they had ertapenem resistance, suggesting porin loss. At 8+8 mg/L, activity extended to > 90% of Enterobacterales with OXA-48 and KPC carbapenemases, although the MICs for KPC producers belonging to the international Klebsiella pneumoniae ST258 lineage were higher; metallo-β-lactamase producers remained resistant. Cefepime/tazobactam was less active than ceftolozane/tazobactam against Pseudomonas aeruginosa with AmpC de-repression or high-level efflux but achieved wider antipseudomonal coverage than piperacillin/tazobactam. Activity against other non-fermenters was species-specific.. Overall, cefepime/tazobactam had a spectrum exceeding those of piperacillin/tazobactam and ceftolozane/tazobactam and resembling or exceeding that of carbapenems. Used as a 'new-combination of old-agents' it has genuine potential to be 'carbapenem-sparing'.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Cefepime; Cephalosporins; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Microbial Sensitivity Tests; Piperacillin, Tazobactam Drug Combination; Pseudomonas aeruginosa; Tazobactam

Topics: Adenocarcinoma; Aged; Cefazolin; Cefepime; Diabetes Mellitus, Type 2; Drug Resistance, Microbial; Drug Resistance, Multiple, Bacterial; Flavobacteriaceae; Gram-Negative Bacterial Infections; Humans; Immunocompromised Host; Kidney Failure, Chronic; Male; Pancreatic Neoplasms; Pancreatitis; Peritoneal Dialysis; Piperacillin, Tazobactam Drug Combination; Sleep Apnea Syndromes

Stenotrophomonas maltophilia (S. maltophilia) is an important nosocomial bacterial pathogen. However, the clinical features of children with S. maltophilia infection, the predisposing factors, and the antibiotic susceptibility of the bacteria have not been fully evaluated.In this study, the data of children with S. maltophilia infection from the West China Second University Hospital of Sichuan University (Chengdu, China) between July 2010 and October 2017 were collected and analyzed. The clinical features of enrolled children, the predisposing factors, and the antibiotic susceptibility were reported.In total, infection of S. maltophilia was identified in 128 patients. Most of these patients were under 1 year old (67.2%) and were mainly diagnosed as pneumonia (69%). A large proportion had underlying diseases (45.3%), received immunosuppressive therapy (53.1%), had undergone invasive operations (41.4%), had a history of carbapenem antibiotics use within 7 days before culture acquisition (54.7%), history of intensive care unit (ICU) hospitalization within previous 30 days (34.4%), and other risk factors. In particular, invasive operation (95% confidence interval [CI]: 1.125-14.324, P = .032), especially mechanical ventilation (95% CI: 1.277-20.469, P = .021), and ICU admission (95% CI: 1.743-22.956, P = .005) were independent risk factors for the children to develop severe S. maltophilia infection. As for antibiotic susceptibility, trimethoprim sulfamethoxazole (TMP-SMX), piperacillin tazobactam, ticarcillin clavulanate, and ceftazidime exhibited strong antibacterial activities against S. maltophilia, the susceptibility rates were 97.5%, 86.7%, 92.9%, and 81.5%, respectively.We report the clinical features of children with S. maltophilia infection, the predisposing factors and the antibiotic susceptibility. TMP-SMX can continue to be the first choice for the treatment of S. maltophilia infection. Piperacillin tazobactam, ticarcillin clavulanate, and the third generation cephalosporins can be used as alternative drugs.

Topics: Age Distribution; Anti-Bacterial Agents; Carbapenems; Ceftazidime; Child, Preschool; China; Clavulanic Acids; Comorbidity; Female; Gram-Negative Bacterial Infections; Hospitalization; Humans; Immunosuppressive Agents; Infant; Intensive Care Units, Pediatric; Length of Stay; Male; Piperacillin, Tazobactam Drug Combination; Respiration, Artificial; Retrospective Studies; Risk Factors; Sex Distribution; Stenotrophomonas maltophilia; Surgical Procedures, Operative; Ticarcillin; Trimethoprim, Sulfamethoxazole Drug Combination

Cefoperazone-sulbactam (CS) and piperacillin-tazobactam (TZP) are used in the treatment of Gram-negative nosocomial infections (NIs). We aimed to compare the effects of these two antibiotics on mortality and treatment success. Patients treated with CS or TZP empirically for at least three days with suspicion of NI were included in this retrospective study. In total, 308 (154 patients in both treatment arms) patients were analyzed. Treatment success rate in CS and TZP group respectively (50% vs 51.2%,

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Cefoperazone; Cross Infection; Drug Combinations; Drug Resistance, Multiple, Bacterial; Female; Gram-Negative Bacterial Infections; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Sulbactam

A 52-year-old female patient was admitted to our clinic with complaints of cough, sputum, fever and fatigue. The patient has been receiving immunosuppressive therapy for thrombocytopenic purpura for 5 years.. Inspiratory crackles were heard on both hemithorax. Oxygen saturation measured with the pulse oximeter was 97%. Chest X-ray showed diffuse reticular opacities that were more prominent in the upper zones of both lungs. WBC counts were 17,600 mm. The patient was hospitalized with suspicion of opportunistic pulmonary infections and cavitary lung disease. After the empirical treatment of intravenous piperacillin-tazobactam and oral clarithromycin, her clinical and radiological findings significantly regressed, and she was discharged with outpatient follow-up.. This is the first example of cavitary pneumonia due to. Una mujer de 52 años llegó a la clínica con tos, esputo, fiebre y fatiga. El paciente estuvo recibiendo terapia inmunosupresora durante 5 años para el tratamiento de la púrpura trombocitopénica.. se escucharon crepitaciones inspiratorias en ambos hemitórax. La saturación de oxígeno fue del 97%. La radiografía de tórax mostró opacidades reticulares difusas que eran más prominentes en las zonas superiores de ambos pulmones. Los recuentos de leucocitos fueron de 17,600 mm. La paciente fue hospitalizado con una sospecha de infección oportunista pulmonar y enfermedad pulmonar cavitaria. Después del tratamiento empírico de piperacilina-tazobactam intravenosa y claritromicina oral, los síntomas y signos retrocedieron significativamente, y fue dada de alta con seguimiento ambulatorio.. este es el primer registro de neumonía cavitaria causado por

Topics: Anti-Bacterial Agents; Clarithromycin; Delftia acidovorans; Female; Gram-Negative Bacterial Infections; Humans; Immunocompromised Host; Lung; Middle Aged; Piperacillin, Tazobactam Drug Combination; Pneumonia, Bacterial; Tomography, X-Ray Computed

Piperacillin/tazobactam (TZP) has been associated with nephrotoxicity in patients receiving vancomycin. Its impact on nephrotoxicity in patients with Gram-negative bacteraemia (GNB) is unclear. This study evaluated the impact of TZP on nephrotoxicity in patients with GNB. This retrospective cohort included patients aged ≥18 years receiving ≥48 h of therapy for bacteraemia due to Escherichia coli, Pseudomonas aeruginosa, Enterobacter, Klebsiella, Acinetobacter or Stenotrophomonas maltophilia from 1/01/2008-8/31/2011. Patients with baseline serum creatinine (SCr) ≥3.5 mg/dL, polymicrobial infection or recurrent bacteraemia were excluded. Nephrotoxicity was defined as a ≥0.5 mg/dL increase in SCr or ≥50% increase from baseline for ≥2 consecutive days. Any variable demonstrating a 10% change in exposure effect was retained in the final model. All variables biologically reasonable causes of nephrotoxicity were also considered for inclusion. The median age of the cohort (n = 292) was 76 years; 38.0% had a cancer diagnosis and ICU residence was common (21.9%). There was no difference in nephrotoxicity incidence based on days of TZP received (0 days, 13.6%; 1-2 days, 14.7%; 3-4 days, 6.9%; ≥5 days, 16.7%; P = 0.71). In multivariable analysis, baseline SCr, total body weight and vasopressor use were independently associated with nephrotoxicity. Duration of TZP was not associated with nephrotoxicity in multivariable analysis (1-2 days, OR = 0.91, 95% CI 0.39-2.12; 3-4 days, OR = 0.48, 95% CI 0.10-2.46; ≥5 days, OR = 0.57, 95% CI 0.11-3.02). In this cohort of GNB patients, duration of TZP was not associated with nephrotoxicity.

Topics: Acute Kidney Injury; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; beta-Lactamase Inhibitors; Female; Gram-Negative Bacterial Infections; Humans; Incidence; Male; Middle Aged; Piperacillin, Tazobactam Drug Combination; Retrospective Studies

Topics: Aged; Alcaligenes faecalis; Bacteremia; Bordetella; Bordetella Infections; Breast Neoplasms; Catheter-Related Infections; Coinfection; Female; Gram-Negative Bacterial Infections; Humans; Immunocompromised Host; Neoplasm Metastasis; Piperacillin, Tazobactam Drug Combination

An increase in the prevalence of antimicrobial resistance among gram-negative pathogens has been noted recently. A challenge in empiric treatment of complicated intra-abdominal infection (cIAI) is identifying initial appropriate antibiotic therapy, which is associated with reduced length of stay and mortality compared with inappropriate therapy. The objective of this study was to assess the cost-effectiveness of ceftolozane/tazobactam + metronidazole compared with piperacillin/tazobactam (commonly used in this indication) in the treatment of patients with cIAI in UK hospitals.. A decision-analytic Monte Carlo simulation model was used to compare costs (antibiotic and hospitalization costs) and quality-adjusted life years (QALYs) of patients infected with gram-negative cIAI and treated empirically with either ceftolozane/tazobactam + metronidazole or piperacillin/tazobactam. Bacterial isolates were randomly drawn from the Program to Assess Ceftolozane/Tazobactam Susceptibility (PACTS) database, a surveillance database of non-duplicate bacterial isolates collected from patients in the UK infected with gram-negative pathogens. Susceptibility to initial empiric therapy was based on the measured susceptibilities reported in the PACTS database.. Ceftolozane/tazobactam + metronidazole was cost-effective when compared with piperacillin/tazobactam, with an incremental cost-effectiveness ratio (ICER) of £4,350/QALY and 0.36 hospitalization days/patient saved. Costs in the ceftolozane/tazobactam + metronidazole arm were £2,576/patient, compared with £2,168/patient in the piperacillin/tazobactam arm. The ceftolozane/tazobactam + metronidazole arm experienced a greater number of QALYs than the piperacillin/tazobactam arm (14.31/patient vs 14.21/patient, respectively). Ceftolozane/tazobactam + metronidazole remained cost-effective in one-way sensitivity and probabilistic sensitivity analyses.. Economic models can help to identify the appropriate choice of empiric therapy for the treatment of cIAI. Results indicated that empiric use of ceftolozane/tazobactam + metronidazole is cost-effective vs piperacillin/tazobactam in UK patients with cIAI at risk of resistant infection. This will be valuable to commissioners and clinicians to aid decision-making on the targeting of resources for appropriate antibiotic therapy under the premise of antimicrobial stewardship.

Topics: Anti-Bacterial Agents; Bacteriological Techniques; Cephalosporins; Clinical Protocols; Drug Combinations; Drug Therapy, Combination; Female; Gram-Negative Bacterial Infections; Humans; Intraabdominal Infections; Male; Metronidazole; Models, Econometric; Monte Carlo Method; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Quality-Adjusted Life Years; Tazobactam; United Kingdom

Despite their common use as an empirical combination therapy for the better part of a decade, there has been a recent association between combination therapy with vancomycin and piperacillin-tazobactam and high rates of acute kidney injury (AKI). The reasons for this increased association are unclear, and this analysis was designed to investigate the association. Retrospective cohort and case-control studies were performed. The primary objective was to assess if there is an association between extended-infusion piperacillin-tazobactam in combination with vancomycin and development of AKI. The secondary objectives were to identify risk factors for AKI in patients on the combination, regardless of infusion strategy, and to evaluate the impact of AKI on clinical outcomes. AKI occurred in 105/320 (33%) patients from the cohort receiving combination therapy with vancomycin and piperacillin-tazobactam, with similar rates seen in those receiving intermittent (53/160 [33.1%]) and extended infusions (52/160 [32.5%]) of piperacillin-tazobactam. Independent risk factors for AKI in the cohort included having a documented Gram-positive infection, the presence of sepsis, receipt of a vancomycin loading dose (odds ratio [OR], 2.22; 95% confidence interval [CI], 1.05 to 4.71), and receipt of any concomitant nephrotoxin (OR, 2.44; 95% CI, 1.41 to 4.22). For at-risk patients remaining on combination therapy, the highest rates of AKI occurred on days 4 (10.7%) and 5 (19.3%). The incidence of AKI in patients on combination therapy with vancomycin and piperacillin-tazobactam is high, occurring in 33% of patients. Receipt of piperacillin-tazobactam as an extended infusion did not increase this risk. Modifiable risk factors for AKI include receipt of a vancomycin loading dose, concomitant nephrotoxins, and longer durations of therapy.

Topics: Acute Kidney Injury; Adult; Aged; Anti-Bacterial Agents; Case-Control Studies; Drug Therapy, Combination; Female; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Logistic Models; Male; Michigan; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Vancomycin

In liver transplant (LT) recipients, surgical site infection (SSI) represents an important cause of morbidity and mortality.. This study measures the impact of a multimodal approach to the incidence of surgical site infection in LT recipients.. All of the LT recipients in our department were registered on the national database in solid organ transplant. A study was performed in two analytical-interventional phases. Phase 1 took place between July 14, 2009, and February 20, 2014. Phase 2 took place between February 21, 2014, and July 15, 2015. The multimodal change implemented during phase 1 was that 0.5% alcoholic chlorhexidine and ether were applied to the surgical field; surgical prophylaxis was primarily with ampicillin/sulbactam plus cefazolin. In phase 2, 2% alcoholic chlorhexidine alone was applied to the surgical field. The prior standard prophylaxis was changed to piperacillin tazobactam administered during surgery as a continuous infusion of 13.5 g over 8 hours with a pre-incision loading dose of 4.5 g. The loading dose of piperacillin tazobactam was combined with a single dose of gentamicin of 5 mg/kg.. One hundred eight patients have received transplants since the start of the program: 82 patients during phase one and 26 patients during phase two. During phase 1, 13 cases of SSI were recorded, representing a rate of 15.85 per 100 transplants. Sixteen micro-organisms were isolated during phase 1, of which 12 corresponded to gram-negative bacilli. With regard to resistance profiles, 13 showed multidrug resistant and extensively drug resistant profiles. During phase 2, no cases of SSI were recorded (relative risk = 0.158 [95% confidence interval 0.0873-0.255], P = .0352].. A multimodal approach allowed for the reduction of the incidence of SSI in LTs and offered a protective strategy.

Topics: Administration, Cutaneous; Adult; Ampicillin; Anti-Bacterial Agents; Anti-Infective Agents, Local; Antibiotic Prophylaxis; Cefazolin; Chlorhexidine; Drug Administration Schedule; Drug Therapy, Combination; Ether; Female; Gentamicins; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Infusions, Intravenous; Liver Transplantation; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sulbactam; Surgical Wound Infection; Transplant Recipients

Introduction To enhance the probability of pharmacodynamic target attainment, piperacillin-tazobactam can be administered as either a continuous or extended-infusion dosage regimen for the treatment of gram-negative infections. Four hour extended-infusions of piperacillin-tazobactam 3.375 g administered intravenously (IV) every 8 h have been widely studied as an alternative to conventional, intermittent dosage regimens with largely favorable outcomes. Objective To assess the clinical and economic impact of a novel 3-h extended-infusion piperacillin-tazobactam dosing strategy for the treatment of gram-negative infections. Setting 433-bed community hospital in Lexington, KY. Methods Retrospective cohort study before and after the implementation of an alternative dosing protocol using a 3-h infusion of piperacillin-tazobactam 3.375 g IV every 6 h. Main outcome measures The primary outcome was in-hospital mortality. Secondary outcomes include length of stay, ICU length of stay, 30-day all-cause hospital readmissions, total cost per admission, complications, and a composite of in-hospital mortality and readmission within 30 days of discharge. Results Readmission within 30 days of hospital discharge was significantly reduced in the extended-infusion arm (1.2 vs. 13.7 %, P = 0.002). A composite endpoint of death or readmission was lower among patients who received the extended-infusion dosing regimen [ORadj 0.20; 95 % CI (0.07-0.57)]. However this was likely driven by reductions in readmission. Conclusion An alternative regimen of extended-infusion piperacillin-tazobactam resulted in a significant reduction in 30-day all-cause hospital readmission. These results indicate that 3-h infusions of piperacillin-tazobactam 3.375 g IV every 6 h may represent a clinically effective alternative to other commonly used regimens and results in fewer readmissions within 30 days.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Cohort Studies; Delayed-Action Preparations; Drug Administration Schedule; Female; Gram-Negative Bacterial Infections; Humans; Infusions, Intravenous; Kentucky; Male; Middle Aged; Patient Readmission; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Treatment Outcome

Stenotrophomonas maltophilia is a bacterial pathogen associated with health-care associated infections, particularly in immunocompromised patients. Members of the fluoroquinolone drug class are frequently used to treat S. maltophilia infection; however, S. maltophilia resistance to fluoroquinolones, especially levofloxacin, has been increasing.. We sought to identify risk factors associated with levofloxacin resistance using a case-control study. We examined sputum from 76 S. maltophilia-positive patients admitted to our hospital between January 1, 2010 and June 30, 2011. Case groups were defined as patients who had S. maltophilia infections resistant to levofloxacin, and control groups were defined as patients who had S. maltophilia infections susceptible to levofloxacin treatment. Patient information including demographics, previous antibiotic use, and other traits were recorded. In addition, S. maltophilia isolates from patient sputum were assessed for antibiotic resistance as well as for the presence of genes associated with drug resistance.. Previous antibiotic treatment with first- or second-generation cephalosporin was found more often in the levofloxacin-susceptible group; by contrast, previous piperacillin/tazobactam treatment occurred more often in the levofloxacin-resistant group. Three genes associated with drug resistance, including SmeA, SmeD, and SpgM were not significantly different between these groups.. Piperacillin/tazobactam treatment is associated with subsequent isolation of levofloxacin-resistant S. maltophilia from the respiratory tract.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Case-Control Studies; Cross Infection; Drug Resistance, Bacterial; Drug Utilization; Female; Gram-Negative Bacterial Infections; Hospitals; Humans; Levofloxacin; Male; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Respiratory Tract Infections; Risk Factors; Sputum; Stenotrophomonas maltophilia

Febrile neutropenia (FN) is a life-threatening complication of cancer therapy, and initial ineffective therapy is associated with poor outcomes. Piperacillin/tazobactam (PTZ) is a commonly used empiric antibiotic for the treatment of FN, but resistance among Gram-negative pathogens is well described. We conducted a retrospective case-control study to identify risk factors for PTZ-resistant (PTZ-R) Gram-negative isolates.. Hematology/oncology patients with FN from November 2007 to November 2013 with a positive culture for Gram-negative bacilli were divided into two groups: PTZ-sensitive (PTZ-S) and PTZ-R. A multivariable model using logistic regression was constructed to identify risk factors for PTZ-R.. A total of 171 patients were included (25 PTZ-R, 146 PTZ-S), yielding a 14.6 % resistance rate. Thirty-day all-cause mortality was significantly higher in the PTZ-R group (29 vs 11 %, P = 0.024). Multivariable analysis yielded intensive care unit (ICU) status (odds ratio (OR) 20.18; 95 % confidence interval (CI) 1.03-397.35; P = 0.048), antibiotics for > 14 days in the previous 90 days (OR 6.02; CI 1.17-30.93; P = 0.032), and respiratory source (OR 13.65; CI 1.14-163.57; P = 0.039) as significant risk factors for PTZ-R, and the receiver operating characteristic area under the curve of the model was 0.894. Among PTZ-R isolates, 88 % were sensitive to meropenem and 100 % were sensitive to amikacin.. Given the high mortality rates in the PTZ-R group, a risk-factor-guided approach driven by this multivariable model may help identify patients that could benefit from amikacin combination therapy to help optimize empiric therapy in this setting.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Case-Control Studies; Drug Resistance, Multiple, Bacterial; Febrile Neutropenia; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Hematologic Neoplasms; Humans; Male; Middle Aged; Neoplasms; Penicillanic Acid; Penicillin Resistance; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Risk Factors; Young Adult

Four cases of central venous catheter-related Methylobacterium radiotolerans infection are presented here. The patients were all long-term catheter carriers with an underlying diagnosis of leukemia, and they mostly manifested fevers. The isolated bacterial strains all showed far better growth on buffered charcoal yeast extract agar during the initial isolation and/or subcultures than they did on sheep blood or chocolate agar. This microbiological feature may improve the culture recovery of this fastidious pink Gram-negative bacillus that has rarely been isolated in clinical microbiology laboratories.

Topics: Aged, 80 and over; Anti-Bacterial Agents; Catheter-Related Infections; Child; Ciprofloxacin; Female; Gram-Negative Bacterial Infections; Humans; Levofloxacin; Male; Methylobacterium; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Young Adult

We sought to describe a case of pharmacodynamically-optimized dosing of piperacillin-tazobactam in a patient that cleared their infections after treatment with high-dose, extended-infusion piperacillin-tazobactam and summarize the literature on the benefits of extended-infusion of beta-lactams.. At an outside hospital, a 78 year-old male presented with fevers and shortness of breath. He was empirically initiated on standard doses of vancomycin and piperacillin-tazobactam for suspected pneumonia and sepsis. Blood and sputum cultures identified Elizabethkingia meningosepticum sensitive only to piperacillin-tazobactam by E-test susceptibility testing. After 10 days of empiric therapy with piperacillin-tazobactam dosed at 3.375 g IV every 8 h over 30 min, the patient transferred to our institution and was initiated on piperacillin-tazobactam at 3.375 g IV every 8 h administered as a 4 h infusion. The patient failed to improve; piperacillin-tazobactam was changed to 4.5 g IV over 4 h every 8 h and later changed to the hospital protocol dose of 3.375 g IV over 4 h every 6 h. The patient achieved negative blood cultures within 24 h of optimized dosing.. We present the first case to our knowledge that describes failure to respond and subsequent response within a single patient where beta-lactam dosing was altered to optimize pharmacokinetics and pharmacodynamics (PK-PD). Our patient received non-standard dose-escalation for piperacillin-tazobactam. Drug exposure was estimated post-hoc utilizing robust mathematical simulations to describe alterations in disposition over time. This case demonstrates that extended-infusion administration of beta-lactams may provide improved microbiological activity.

Topics: Aged; Anti-Bacterial Agents; Bacteremia; beta-Lactamases; beta-Lactams; Endocarditis; Gram-Negative Bacterial Infections; Humans; Infusions, Intravenous; Male; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination

The purpose of this study was to review central line-associated blood stream infection (CLABSI) data from a surgical trauma intensive care unit to better understand patient risk factors, pathogens, and treatment interventions. We performed a retrospective review of all surgical ICU patients who met the Centers for Disease Control definition for Gram-negative CLABSI from 2006 through 2013. Demographics, pathogens, interventions, and outcomes were evaluated. A total of 40 patients were included with an average age of 49.9 ± 19 years and 72.5 per cent male. The average length of central venous line (CVL) was 11 ± 5.9 days with average time from line placement to positive culture 9.4 ± 6.8 days. Most common organisms were Enterobacter species (37.5%) with 17.8 per cent of all cultured organisms considered multidrug resistant. Piperacillin-tazobactam (67.5%) was the most commonly used antibiotic. Overall mortality rate was 22.5 per cent. A total of 11 patients who developed a recurrence did so at 10.7 ± 8 days and were similar to those without recurrence. Predominant pathogens associated with surgical trauma intensive care unit CLABSI in this study are different from those Gram-negative bacteria associated with published studies in the general hospital population. Further investigation into risk factors for infection and relapse is important to minimize such consequences. Understanding appropriate line placement and use as well as clarifying optimal duration of therapy is integral in improving outcomes.

Topics: Adult; Aged; Bacteremia; Catheter-Related Infections; Catheterization, Central Venous; Cohort Studies; Comprehension; Cross Infection; Female; Follow-Up Studies; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Hospital Mortality; Humans; Incidence; Intensive Care Units; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Risk Assessment; Survival Rate; Tertiary Care Centers; Treatment Outcome; Urban Population; Virginia

Patients with asplenia are prone to overwhelming infections due to encapsulated organisms. We report a 62-year-old man presenting with fever and weakness. His medical history was significant for splenectomy and owning a dog as pet. The patient on examination had evidence of animal bite and scratch marks on his lower extremity and developed dry gangrene of multiple digits of his upper extremity soon after admission. The patient's initial blood cultures were positive for Gram-negative rods, but no organism was identified. Capnocytophaga canimorsus was the suspected organism and the patient's antibiotics were tailored accordingly, with good clinical recovery. The patient' blood cultures finally grew C canimorsus on day 20 for which the patient had already been treated with prior clinical judgement. Physicians should be aware of this organism in the setting of sepsis in patients with asplenia and use appropriate antibiotics until further results are obtained.

Topics: Animals; Anti-Bacterial Agents; Capnocytophaga; Dogs; Gram-Negative Bacterial Infections; Humans; Immunocompromised Host; Male; Middle Aged; Penicillanic Acid; Pets; Piperacillin; Piperacillin, Tazobactam Drug Combination; Postoperative Complications; Splenectomy; Zoonoses

Piperacillin-tazobactam (PTZ) is frequently used as empirical and targeted therapy for Gram-negative sepsis. Time-dependent killing properties of PTZ support the use of extended-infusion (EI) dosing; however, studies have shown inconsistent benefits of EI PTZ treatment on clinical outcomes. We performed a retrospective cohort study of adult patients who received EI PTZ treatment and historical controls who received standard-infusion (SI) PTZ treatment for presumed sepsis syndromes. Data on mortality rates, clinical outcomes, length of stay (LOS), and disease severity were obtained. A total of 843 patients (662 with EI treatment and 181 with SI treatment) were available for analysis. Baseline characteristics of the two groups were similar, except for fewer female patients receiving EI treatment. No significant differences between the EI and SI groups in inpatient mortality rates (10.9% versus 13.8%; P = 0.282), overall LOS (10 versus 12 days; P = 0.171), intensive care unit (ICU) LOS (7 versus 6 days; P = 0.061), or clinical failure rates (18.4% versus 19.9%; P = 0.756) were observed. However, the duration of PTZ therapy was shorter in the EI group (5 versus 6 days; P < 0.001). Among ICU patients, no significant differences in outcomes between the EI and SI groups were observed. Patients with urinary or intra-abdominal infections had lower mortality and clinical failure rates when receiving EI PTZ treatment. We did not observe significant differences in inpatient mortality rates, overall LOS, ICU LOS, or clinical failure rates between patients receiving EI PTZ treatment and patients receiving SI PTZ treatment. Patients receiving EI PTZ treatment had a shorter duration of PTZ therapy than did patients receiving SI treatment, and EI dosing may provide cost savings to hospitals.

Topics: Aged; Anti-Bacterial Agents; Cost-Benefit Analysis; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Infusions, Intravenous; Length of Stay; Male; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Sepsis; Survival Analysis; Syndrome; Tertiary Healthcare

Nosocomial pneumonia remains an important cause of mortality and morbidity worldwide. Surveillance programs play an important role in the identification of common etiologic agents and local patterns of antimicrobial resistance.. In this study we determined the frequency and antimicrobial susceptibility of pathogens isolated from patients with nosocomial pneumonia during 2009 to 2011.. A total of 642 bacteria were isolated from 516 suspected samples. Acinetobacter baumannii (21.1%, n = 136), was the commonest isolated pathogen followed by Pseudomonas aeruginosa (17.4%, n = 112), Staphylococcus aureus (15.8%, n = 102) and enterococci (8.4% n = 54). The most effective therapeutic agents against A. baumannii were polymyxin B (95.5% susceptible), ceftriaxone/tazobactam (72% susceptible) and levofloxacin (52.9% susceptible). Polymixin B (89.2% susceptible), ceftriaxone/tazobactam (89.2% susceptible) and piperacillin-tazobactam (80.3% susceptible) were found to be the most active agents against P. aeruginosa. Extended-spectrum beta-lactamases were detected among isolates of K. pneumoniae (45.4%) and E. coli (20.3%). Overall, the prevalence of methicillin-resistant S. aureus and vancomycin resistant enterococci were 80.4% and 40.7% respectively. Linezolid was found to be the most active antibiotic against these pathogens. The etiology of 50% of the nosocomial infection cases was polymicrobial.. The combination of ceftriaxone/tazobactam seems to be beneficial agent against multidrug-resistant Gram-negative bacilli isolated form respiratory tract infections. The results of our study can be used for guiding appropriate empiric therapy in this geographic region.

Topics: Acinetobacter baumannii; Anti-Bacterial Agents; Ceftriaxone; Cross Infection; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Hospitals; Humans; Iran; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia, Bacterial; Polymyxin B; Prevalence; Pseudomonas aeruginosa; Respiratory Tract Infections; Sputum; Staphylococcus aureus

In 2009, the Study for Monitoring Antimicrobial Resistance Trends (SMART) was expanded to include surveillance of Gram-negative pathogens causing urinary tract infections (UTIs) in the Asia-Pacific region. A total of 1762 isolates were collected from 38 centers in 11 countries from patients with UTIs in 2009 and 2010. In vitro susceptibilities were determined by the broth microdilution method and susceptibility profiles were determined using minimum inhibitory concentration (MIC) interpretive criteria, as recommended by the Clinical and Laboratory Standards Institute (CLSI) in 2010 (M100-S20), in 2011 (M100-S21), and in 2012 (M100-S22). Enterobacteriaceae comprised 86.0% of the isolates, of which Escherichia coli (56.5%) and Klebsiella pneumoniae (13.8%) were the two most common species. Amikacin was the most effective antibiotic (91.7%), followed by ertapenem (86.9%), imipenem (86.6%), and piperacillin-tazobactam (84.9%). Rates of susceptibility were 50.3% for cefoxitin and ranged from 50.3% to 74.2% for the third- and fourth-generation cephalosporins. For ciprofloxacin and levofloxacin, the susceptibility rates were 51.4% and 54.4%, respectively. Extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae comprised 28.2% of all isolates. We also found a high rate of resistance to carbapenems among Acinetobacter baumannii and Pseudomonas aeruginosa causing UTI. Interestingly, according to 2012 CLSI breakpoints, approximately 33.4% of ESBL producers were still susceptible to ceftazidime. However, this in vitro efficacy of ceftazidime needs to be validated in vivo by clinical data. The lowered CLSI interpretive breakpoints for piperacillin-tazobactam, carbapenems, and some cephalosporins in 2011-2012 for Enterobacteriaceae resulted in an approximate 5% drop in susceptibility rates for each drug, with the exception of imipenem for which the susceptibility rate dropped from 99.4% according to 2010 criteria to 91.2% according to 2011 criteria. With the updated CLSI criteria, the antimicrobial resistance threat from UTI pathogens in the Asia Pacific area was revealed to be more prominent.

Topics: Amikacin; Anti-Bacterial Agents; Asia; Australasia; beta-Lactamases; beta-Lactams; Carbapenems; Ceftazidime; Drug Resistance, Bacterial; Ertapenem; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prevalence; Prospective Studies; Urinary Tract Infections

Studies evaluating the outcomes of an extended-infusion (EI) piperacillin-tazobactam dosing strategy in specific cohorts of critically ill patients are lacking. A retrospective, pre-implementation and post-implementation study of 148 critically ill patients was conducted to compare EI and traditional infusion piperacillin-tazobactam. In this retrospective study, the EI piperacillin-tazobactam dosing strategy was associated with improved 30-day mortality. EI piperacillin-tazobactam may be an effective alternative to TI of piperacillin-tazobactam among critically ill patients treated for suspected gram-negative infections.

Topics: Aged; Anti-Bacterial Agents; Critical Illness; Drug Administration Schedule; Female; Gram-Negative Bacterial Infections; Humans; Infusions, Intravenous; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies

Animal bites are typically harmless, but in rare cases infections introduced by such bites can be fatal. Capnocytophaga canimorsus, found in the normal oral flora of dogs, has the potential to cause conditions ranging from minor cellulitis to fatal sepsis. The tendency of C. canimorsus infections to present with varied symptoms, the organism's fastidious nature, and difficulty of culturing make this a challenging diagnosis. Rarely, bacterial cytotoxins such as those produced by C. canimorsus may act as causative agents of TTP, further complicating the diagnosis. Early recognition is crucial for survival, and the variability of presentation must be appreciated. We present the first known case of C. canimorsus infection resulting in TTP that initially presented as splenic infarction.. 72-year-old Caucasian male presented with a four-day history of abdominal pain, nausea, vomiting, diarrhea, and intermittent confusion. On presentation, vital signs were stable and the patient was afebrile. Physical examination was unremarkable apart from petechiae on the inner left thigh, and extreme diffuse abdominal pain to palpation and percussion along with positive rebound tenderness. Initial investigations revealed leukocytosis with left shift and thrombocytopenia, but normal liver enzymes, cardiac enzymes, lipase, INR and PTT. Abdominal CT demonstrated a non-enhancing spleen and hemoperitoneum, suggesting complete splenic infarction. Although the patient remained afebrile, he continued deteriorating over the next two days with worsening thrombocytopenia. After becoming febrile, he developed microangiopathic hemolytic anemia and hemodynamic instability, and soon after was intubated due to hypoxic respiratory failure and decreased consciousness. Plasma exchange was initiated but subsequently stopped when positive blood cultures grew a gram-negative organism. The patient progressively improved following therapy with piperacillin-tazobactam, which was switched to imipenem, then meropenem when Capnocytophaga was identified.. There is a common misconception amongst practitioners that the presence of systemic infection excludes the possibility of TTP and vice versa. This case emphasizes that TTP may occur secondary to a systemic infection, thereby allowing the two processes to coexist. It is important to maintain a wide differential when considering the diagnosis of either TTP or C. canimorsus infection since delays in treatment may have fatal consequences.

Topics: Aged; Animals; Anti-Bacterial Agents; Bites and Stings; Capnocytophaga; Dogs; Gram-Negative Bacterial Infections; Humans; Imipenem; Male; Meropenem; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Purpura, Thrombotic Thrombocytopenic; Splenic Infarction; Thienamycins

Administration of β-lactam antibiotics by extended infusion optimizes the pharmacodynamic properties and bactericidal activity of these agents resulting in a potential improvement in patient outcomes and reduction in drug expenditure. Consequently, a pharmacist-led piperacillin-tazobactam extended 4-hour infusion guideline was implemented hospital-wide at a 500-bed academic medical center. Each piperacillin-tazobactam infusion was prospectively monitored for 5 weeks to ensure accurate administration and identify barriers to guideline adherence. Overall, a total of 103 patients received 1215 doses of piperacillin-tazobactam by extended infusions. In all, 98% of the doses were administered at the correct extended infusion rate and 94% of the doses were given at the scheduled time. There were a total of 20 missed doses and 53 delayed doses, accounting for 2% and 4% of the total administered doses, respectively. The primary barrier to adherence was the patient not being on the unit at the time of the scheduled dose followed by the piperacillin-tazobactam dose not being available on the floor. While insufficient power prevented meaningful evaluation of clinical outcomes, we anticipate a conservative annual estimated cost savings of $108,529. Key elements contributing to our success included consistent pharmacy leadership, multidisciplinary involvement, thorough inservicing to health care professionals, hospital-wide implementation, and extensive quality assurance monitoring.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Guideline Adherence; Health Plan Implementation; Humans; Infusions, Intravenous; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Time Factors; Young Adult

To compare the effectiveness of extended-infusion piperacillin-tazobactam with that of similar-spectrum, nonextended-infusion [H9252]-lactam antibiotics in the treatment of gram-negative infections.. Multicenter, retrospective medical record review.. Fourteen hospitals throughout the United States.. A total of 359 adults treated for gram-negative infections between January 1, 2007, and February 28, 2010, with either 4-hour extended-infusion piperacillin-tazobactam (186 patients) or nonextended-infusion comparator antibiotics (173 patients), which consisted of cefepime, ceftazidime, imipenem-cilastatin, meropenem, doripenem, or piperacillin-tazobactam.. Deidentified data were collected on demographics, renal function, Acute Physiology and Chronic Health Evaluation II score, chronic health conditions, source of infection and type of organism, intensive care unit (ICU) length of stay, total length of stay, type and duration of antimicrobial therapy, and in-hospital mortality. The primary outcome was mortality rate of the patients receiving extended-infusion piperacillin-tazobactam versus those receiving nonextended-infusion comparator antibiotics. Secondary outcomes were hospital length of stay, ICU length of stay, and total duration of antibiotic therapy. Baseline characteristics were similar between groups, except a significantly lower proportion of patients in the extended-infusion group were treated with a concomitant intravenous aminoglycoside (5.9% vs 16.2%, p<0.01), were infected with Pseudomonas species (22.6% vs 39.9%, p<0.01), or had positive respiratory cultures (30.7% vs 43.4%, p=0.01). Antibiotic duration, hospital length of stay, and ICU length of stay were similar between groups. In-hospital mortality was significantly decreased in the extended-infusion piperacillin-tazobactam group versus those receiving comparator antibiotics (9.7% vs 17.9%, p=0.02). Multivariate analysis confirmed that extended-infusion piperacillin-tazobactam prolonged survival by 2.77 days (p<0.01) and reduced the risk of mortality (odds ratio 0.43, p=0.05).. Pharmacodynamic dosing using extended-infusion piperacillintazobactam demonstrated favorable outcomes, including mortality, when compared with nonextended-infusion, similar-spectrum [H9252]-lactams in the treatment of patients with documented gram-negative infections. Prospective, randomized trials are needed to further corroborate these findings.

Topics: Aged; Anti-Bacterial Agents; Cohort Studies; Female; Gram-Negative Bacterial Infections; Hospital Mortality; Humans; Infusions, Intravenous; Length of Stay; Male; Middle Aged; Multivariate Analysis; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Survival Rate; Time Factors; Treatment Outcome

Sphingomonas paucimobilis, is a yellow-pigmented, aerobic, non fermentative, gram negative motile bacillus. S. paucimobilis which is widely found in nature and hospital environments rarely cause serious or life threatening infections. In this report, a case of hospital acquired bloodstream infection due to S. paucimobilis in a patient with Down syndrome who was on treatment for presumed pneumonia is presented. A one year-old child patient who was a known case of Down syndrome and had previously experienced cardiac surgery was hospitalized and treated for pneumonia. On the 12th day of hospitalization, blood cultures were taken because of a high body temperature. One of the blood cultures was positive for gram-negative rods. After 48 hour of incubation, the sub-cultures on blood agar medium yielded pure growth of a yellow, non-fermentative, gram-negative, rod-shaped bacterium. The microorganism was positive for oxidase, and esculin hydrolysis, while negative for urea and nitrate reduction, citrate utilisation and motility. The isolate had been identified as S. paucimobilis by using Vitek 2 system. The antibiotic susceptibility test was also performed with the same system and the strain was found to be susceptible to piperacillin-tazobactam and other antibiotics. Treatment with intravenous piperacilin-tazobactam (150 mg/kg/day) was initiated. He responded well to the treatment and was discharged after 10 days. This case is reported to emphasize that S. paucimobilis should be kept in mind as a nosocomial infectious agent in patients with Down syndrome and immunosuppressive patients and the infections should be treated according to the sensitivity test results.

Topics: Bacteremia; Cross Infection; Down Syndrome; Gram-Negative Bacterial Infections; Humans; Infant; Male; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia; Sphingomonas

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

The objective of this study was to evaluate the steady-state pharmacokinetics and pharmacodynamics of piperacillin/tazobactam, administered by prolonged infusion, in hospitalised patients requiring antimicrobial therapy. Thirteen patients received 4.5 g every 8 h (q8h), infused over 4 h, and pharmacokinetic parameters were determined by non-compartmental methods. Monte Carlo simulations (10,000 patients) were performed to calculate the cumulative fraction of response (CFR) for seven gram-negative pathogens using minimum inhibitory concentration (MIC) data from the Meropenem Yearly Susceptibility Test Information Collection (2004-2007, USA) as well as the probability of target attainment (PTA) at MICs ranging from 1 microg/mL to 64 microg/mL. The pharmacodynamic target was free piperacillin concentration remaining above the MIC for 50% of the dosing interval. Mean+/-standard deviation maximum and minimum serum concentrations, half-life, volume of distribution at steady-state and systemic clearance of piperacillin were 108.2+/-31.7 microg/mL, 27.6+/-26.3 microg/mL, 2.1+/-1.2 h, 22.1+/-4.0 L and 8.6+/-3.0 L/h, respectively. The CFR was > 90% for Escherichia coli, Serratia marcescens and Citrobacter spp., 88.6% for Enterobacter spp., 87% for Klebsiella pneumoniae, 85.5% for Pseudomonas aeruginosa and 52.8% for Acinetobacter spp. The PTA was 100%, 81.1% and 12.3% at MICs of < or = 16 microg/mL, 32 microg/mL and 64 microg/mL, respectively. Piperacillin/tazobactam 4.5 g q8h infused over 4 h provides excellent target attainment for bacterial pathogens with MICs < or = 16 microg/mL. However, the CFR was < 90% for four of the seven gram-negative pathogens evaluated.

Topics: Adult; Aged; Anti-Bacterial Agents; Female; Gram-Negative Bacterial Infections; Humans; Infusions, Intravenous; Inpatients; Male; Microbial Sensitivity Tests; Middle Aged; Monte Carlo Method; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Serum; United States

The incidence of Gram-negative bacteremia has increased in hematopoietic stem cell transplant (HSCT) recipients. We prospectively collected data from 13 Brazilian HSCT centers to characterize the epidemiology of bacteremia occurring early post transplant, and to identify factors associated with infection due to multi-drug-resistant (MDR) Gram-negative isolates. MDR was defined as an isolate with resistance to at least two of the following: third- or fourth-generation cephalosporins, carbapenems or piperacillin-tazobactam. Among 411 HSCT, fever occurred in 333, and 91 developed bacteremia (118 isolates): 47% owing to Gram-positive, 37% owing to Gram-negative, and 16% caused by Gram-positive and Gram-negative bacteria. Pseudomonas aeruginosa (22%), Klebsiella pneumoniae (19%) and Escherichia coli (17%) accounted for the majority of Gram-negative isolates, and 37% were MDR. These isolates were recovered from 20 patients, representing 5% of all 411 HSCT and 22% of the episodes with bacteremia. By multivariate analysis, treatment with third-generation cephalosporins (odds ratio (OR) 10.65, 95% confidence interval (CI) 3.75-30.27) and being at one of the hospitals (OR 9.47, 95% CI 2.60-34.40) were associated with infection due to MDR Gram-negative isolates. These findings may have important clinical implications in the decision of giving prophylaxis and selecting the empiric antibiotic regimen.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Bacteremia; Brazil; Carbapenems; Cephalosporins; Child; Child, Preschool; Drug Resistance, Multiple; Female; Gram-Negative Bacterial Infections; Hematopoietic Stem Cell Transplantation; Humans; Incidence; Infant; Male; Middle Aged; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Predictive Value of Tests; Prospective Studies; Risk Factors

Antibiotic restriction can be useful in maintaining bacterial susceptibility. The objective of this study was verify if restriction of cefepime, the most frequently used cephalosporin in our neonatal intensive care unit (NICU), would ameliorate broad-spectrum susceptibility of Gram-negative isolates. Nine hundred and ninety-five premature and term newborns were divided into 3 cohorts, according to the prevalence of cefepime use in the unit: Group 1 (n=396) comprised patients admitted from January 2002 to December 2003, period in which cefepime was the most used broad-spectrum antibiotic. Patients in Group 2 (n=349) were admitted when piperacillin/tazobactam replaced cefepime (January to December 2004) and in Group 3 (n=250) when cefepime was reintroduced (January to September 2005). Meropenem was the alternative third-line antibiotic for all groups. Multiresistance was defined as resistance to 2 or more unrelated antibiotics, including necessarily a third or fourth generation cephalosporin, piperacillin/tazobactam or meropenem. Statistics involved Kruskal-Wallis, Mann-Whitney and logrank tests, Kaplan-Meier analysis. Groups were comparable in length of stay, time of mechanical ventilation, gestational age and birth weight. Ninety-eight Gram-negative isolates were analyzed. Patients were more likely to remain free of multiresistant isolates by Kaplan-Meier analysis in Group 2 when compared to Group 1 (p=0.017) and Group 3 (p=0.003). There was also a significant difference in meropenem resistance rates. Cefepime has a greater propensity to select multiresistant Gram-negative pathogens than piperacillin/tazobactam and should not be used extensively in neonatal intensive care.

Topics: Anti-Bacterial Agents; Cefepime; Cephalosporins; Cohort Studies; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacterial Infections; Humans; Infant, Newborn; Infant, Premature; Intensive Care Units, Neonatal; Meropenem; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Thienamycins; Time Factors

This study evaluated the pharmacodynamics of continuous infusion beta-lactams against pulmonary isolates of Gram-negative bacteria from patients managed in intensive care units (ICUs) in the USA. Multiple 10,000-patient Monte Carlo simulations were performed by integrating pharmacokinetic data from healthy individuals with 2408 MICs from the 2002 Intensive Care Unit Surveillance System database. These pharmacodynamic simulations suggested that continuous infusion regimens of cefepime, aztreonam, ceftazidime and piperacillin-tazobactam 13.5 g have the greatest likelihood of achieving pharmacodynamic targets against isolates of Enterobacteriaceae in the ICU. Beta-lactams are unlikely to achieve pharmacodynamic targets against Pseudomonas aeruginosa or Acinetobacter baumannii when administered as monotherapy.

Topics: Anti-Bacterial Agents; Aztreonam; beta-Lactams; Cefepime; Ceftazidime; Cephalosporins; Computer Simulation; Drug Combinations; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Infusions, Intravenous; Intensive Care Units; Microbial Sensitivity Tests; Monte Carlo Method; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia, Bacterial; United States

This study was designed to test whether rotation of antibiotics can reduce colonization with resistant Gram-negative bacilli in a neonatal intensive care unit (NICU).. A monthly rotation of gentamicin, piperacillin-tazobactam, and ceftazidime was compared with unrestricted antibiotic use in side-by-side NICU populations (rotation team vs control team). Pharyngeal and rectal samples were obtained 3 times a week and tested for Gram-negative bacilli resistant to each of the rotation antibiotics. Pulsed-field gel electrophoresis analysis determined the numbers of genetically discordant resistant organisms on each team. The association between colonization with a resistant bacillus (the primary outcome) and team assignment was tested.. A total of 1062 infants were studied during a 1-year period. A total of 10.7% infants on the rotation team versus 7.7% on the control team were colonized with a resistant bacillus. No interteam differences were distinguishable when the numbers of genetically discordant resistant organisms were normalized to the total number of team admissions. The incidence of nosocomial infection and mortality also were similar across teams.. These data indicate that rotation of parenteral antibiotics according to the applied protocol has no detectable effect in decreasing the reservoir of resistant Gram-negative bacilli in a tertiary-care NICU.

Topics: Anti-Bacterial Agents; Ceftazidime; Cross Infection; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Gentamicins; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Infant, Newborn; Intensive Care Units, Neonatal; Microbial Sensitivity Tests; Penicillanic Acid; Pharynx; Piperacillin; Piperacillin, Tazobactam Drug Combination; Rectum