piperacillin--tazobactam-drug-combination and Acute-Disease

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

Meropenem-vaborbactam is a combination carbapenem/beta-lactamase inhibitor and a potential treatment for severe drug-resistant gram-negative infections.. To evaluate efficacy and adverse events of meropenem-vaborbactam in complicated urinary tract infection (UTI), including acute pyelonephritis.. Phase 3, multicenter, multinational, randomized clinical trial (TANGO I) conducted November 2014 to April 2016 and enrolling patients (≥18 years) with complicated UTI, stratified by infection type and geographic region.. Eligible patients were randomized 1:1 to receive meropenem-vaborbactam (2g/2g over 3 hours; n = 274) or piperacillin-tazobactam (4g/0.5g over 30 minutes; n = 276) every 8 hours. After 15 or more doses, patients could be switched to oral levofloxacin if they met prespecified criteria for improvement, to complete 10 days of total treatment.. Primary end point for FDA criteria was overall success (clinical cure or improvement and microbial eradication composite) at end of intravenous treatment in the microbiologic modified intent-to-treat (ITT) population. Primary end point for European Medicines Agency (EMA) criteria was microbial eradication at test-of-cure visit in the microbiologic modified ITT and microbiologic evaluable populations. Prespecified noninferiority margin was -15%. Because the protocol prespecified superiority testing in the event of noninferiority, 2-sided 95% CIs were calculated.. Among 550 patients randomized, 545 received study drug (mean age, 52.8 years; 361 [66.2%] women; 374 [68.6%] in the microbiologic modified ITT population; 347 [63.7%] in the microbiologic evaluable population; 508 [93.2%] completed the trial). For the FDA primary end point, overall success occurred in 189 of 192 (98.4%) with meropenem-vaborbactam vs 171 of 182 (94.0%) with piperacillin-tazobactam (difference, 4.5% [95% CI, 0.7% to 9.1%]; P < .001 for noninferiority). For the EMA primary end point, microbial eradication in the microbiologic modified ITT population occurred in 128 of 192 (66.7%) with meropenem-vaborbactam vs 105 of 182 (57.7%) with piperacillin-tazobactam (difference, 9.0% [95% CI, -0.9% to 18.7%]; P < .001 for noninferiority); microbial eradication in the microbiologic evaluable population occurred in 118 of 178 (66.3%) vs 102 of 169 (60.4%) (difference, 5.9% [95% CI, -4.2% to 16.0%]; P < .001 for noninferiority). Adverse events were reported in 106 of 272 (39.0%) with meropenem-vaborbactam vs 97 of 273 (35.5%) with piperacillin-tazobactam.. Among patients with complicated UTI, including acute pyelonephritis and growth of a baseline pathogen, meropenem-vaborbactam vs piperacillin-tazobactam resulted in a composite outcome of complete resolution or improvement of symptoms along with microbial eradication that met the noninferiority criterion. Further research is needed to understand the spectrum of patients in whom meropenem-vaborbactam offers a clinical advantage.. clinicaltrials.gov Identifier: NCT02166476.

Topics: Acute Disease; Adult; Aged; Anti-Bacterial Agents; Boronic Acids; Drug Combinations; Female; Humans; Intention to Treat Analysis; Male; Meropenem; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Practice Guidelines as Topic; Pyelonephritis; Thienamycins; Urinary Tract Infections; Urine

Antibiotic treatment is an important element in infection control after urgent abdominal surgery. The aim of this study was to determine the therapeutic efficacy of piperacillin-tazobactam versus a combination of 2 antibiotics (metronidazole and gentamicin) in patients undergoing urgent appendicular and/or colorectal surgery.. The study period comprised December 1998 to December 2002. A total of 183 patients who required urgent surgery for colon disease and/or severe acute appendicitis were prospectively and randomly included. Patients were randomly distributed in 2 groups. Group A received piperacillin-tazobactam (4/0.5/8 h/i.v.) and group B received metronidazole (500 mg/i.v./8 h) plus gentamicin (5 mg/kg/i.v./24 h). Treatment was started between 30 and 60 minutes prior to surgery and was continued for at least 3 days.. The incidence of wound infection in patients who underwent surgery for colon disease and acute appendicitis was lower when they were treated with piperacillin-tazobactam (P< .05). The incidence of intraperitoneal abscess in the group of patients who underwent surgery for severe acute appendicitis was lower when they were treated with piperacillin-tazobactam. Microbiological analyses revealed that there was a predominance of infection due to Escherichia coli.. The association of piperacillin-tazobactam was more effective than that of metronidazole and gentamicin in the prevention and treatment of local infection in the treated groups. Therapeutic failure was mainly related to the presence of gram-negative bacteria.

Topics: Acute Disease; Adult; Anti-Bacterial Agents; Anti-Infective Agents; Appendicitis; Drug Administration Schedule; Drug Therapy, Combination; Emergency Treatment; Female; Humans; Male; Metronidazole; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Surgical Wound Infection

Tazobactam/piperacillin (TAZ/PIPC) was given intravenously to 15 children with acute bacterial infections including 1 with purulent tonsillitis, 11 with pneumonia, 3 with acute pyelonephritis (2 cases are omitted from evaluation because of Mycoplasma pneumonia and intramuscular injection of gammaglobulin) Daily dosages per kg bodyweight ranging from 132 to 156 mg were given in 3 divided doses per day for 4 to 7 days. Clinical responses were excellent in 7 (54%), good in 6 (46%), fair and poor in 0, with an overall efficacy rate of 100%. Good bacterial responses were obtained in all of the 8 cases from which pathogens were identified. Any side effect was not observed. The above results suggest that TAZ/PIPC is a useful new antibiotic for the treatment of bacterial infections in children.

Topics: Acute Disease; Bacteria; Child; Child, Preschool; Drug Resistance, Microbial; Drug Therapy, Combination; Female; Humans; Infant; Infusions, Intravenous; Male; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia; Pyelonephritis; Tonsillitis

A drug susceptibility test of the combination drug TAZ/PIPC, which consists of a newly developed beta-lactamase inhibitor, tazobactam (TAZ), and one of penicillin antibiotics, piperacillin (PIPC), with combination ratio of 1:4 in potency, was conducted with stock strains and clinical isolates. The clinical efficacy and safety of its injection was also evaluated in children with a variety of infectious diseases. The results were as follows: 1. In susceptibility test, 114 strains from 4 species of stock strains were treated with 8 drugs, that is, TAZ/PIPC, PIPC, penicillin G (PCG), ampicillin (ABPC), cefotiam (CTM), cefotaxime (CTX), ceftazidime (CAZ), and sulbactam/cefoperazone (SBT/CPZ). Of three clinically isolated species from patients, Staphylococcus aureus (S. aureus) was treated with TAZ/PIPC, PIPC, methicillin (DMPPC), CTM, CTX, and SBT/CPZ, and the others were treated with the same drugs except for DMPPC. The MICs were measured for these bacterial strains inoculated at the concentration of 10(6) CFU/ml. The MIC90 values of TAZ/PIPC against 45 strains of Streptococcus pyogenes (S. pyogenes), one of the stock cultures of Gram-positive cocci, were 0.05 microgram/ml and similar to those of PIPC, CTM, CAZ, and SBT/CPZ. The MICs of TAZ/PIPC for 28 strains of Streptococcus agalactiae (S. agalactiae) were 0.39 microgram/ml and similar to those of PIPC, CTM, CAZ, and SBT/CPZ. As for Gram-negative bacilli, the MIC90 of TAZ/PIPC against 10 strains of Bordetella pertussis (B. pertussis) were 0.10 microgram/ml and similar to those of PIPC. The MIC90 of TAZ/PIPC against 31 strains of Haemophilus influenzae (H. influenzae) were 0.05 microgram/ml and similar to those of PIPC, CTX, and SBT/CPZ. Regarding Gram-positive cocci isolated from patients received this combination drug, the MIC90 of TAZ/PIPC against 2 strains of S. aureus, a non beta-lactamase producing strain and a low-beta-lactamase producing strain, were 0.78 microgram/ml and 3.1 micrograms/ml, respectively; the former value was similar to those of PIPC, DMPPC, CTM, and CTX, and the latter was similar to those of PIPC, DMPPC, CTX, and SBT/CPZ. Of 4 strains of Streptococcus pneumoniae, 2 strains were inhibited at 0.05 microgram/ml, and the others at 1.56 micrograms/ml; both values were similar to those of PIPC, SBT/CPZ. As for Gram-negative bacilli, 6 of 7 strains of H. influenzae did not produce beta-lactamase and 1 strain was a high producer. The MICs of TAZ/PIPC against beta-lactamase nonproducing stra

Topics: Acute Disease; Bacterial Infections; beta-Lactamase Inhibitors; Bordetella pertussis; Bronchitis; Child; Child, Preschool; Drug Therapy, Combination; Female; Haemophilus influenzae; Humans; Infant; Lymphadenitis; Male; Otitis Media, Suppurative; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia, Bacterial; Staphylococcus aureus; Streptococcus agalactiae; Streptococcus pneumoniae; Streptococcus pyogenes; Urinary Tract Infections; Whooping Cough

Coronavirus disease 2019 (COVID-19) has been demonstrated to be the cause of pneumonia. Nevertheless, it has not been reported as the cause of acute myocarditis or fulminant myocarditis.. A 63-year-old male was admitted with pneumonia and cardiac symptoms. He was genetically confirmed as having COVID-19 according to sputum testing on the day of admission. He also had elevated troponin I (Trop I) level (up to 11.37 g/L) and diffuse myocardial dyskinesia along with a decreased left ventricular ejection fraction (LVEF) on echocardiography. The highest level of interleukin-6 was 272.40 pg/ml. Bedside chest radiographs showed typical ground-glass changes indicative of viral pneumonia. Laboratory test results for viruses that cause myocarditis were all negative. The patient conformed to the diagnostic criteria of the Chinese expert consensus statement for fulminant myocarditis. After receiving antiviral therapy and mechanical life support, Trop I was reduced to 0.10 g/L, and interleukin-6 was reduced to 7.63 pg/mL. Moreover, the LVEF of the patient gradually recovered to 68%. The patient died of aggravation of secondary infection on the 33rd day of hospitalization.. COVID-19 patients may develop severe cardiac complications such as myocarditis and heart failure. This is the first report of COVID-19 complicated with fulminant myocarditis. The mechanism of cardiac pathology caused by COVID-19 needs further study.

Topics: Acute Disease; Antiviral Agents; Bacteroides Infections; Betacoronavirus; Biomarkers; Candidiasis; Coronavirus Infections; COVID-19; Drug Combinations; Echocardiography; Fatal Outcome; Humans; Interleukin-6; Lopinavir; Male; Middle Aged; Myocarditis; Pandemics; Piperacillin, Tazobactam Drug Combination; Pneumonia, Viral; Ritonavir; SARS-CoV-2; Stroke Volume; Tomography, X-Ray Computed; Troponin I

Pericardial effusion can develop during any stage of pericarditis, and small effusions that appear rapidly can cause cardiac tamponade. Pyopericardium is a rare aetiology for tamponade. This is a case of an elderly diabetic lady, on steroid therapy for immune thrombocytopenia, who presented with fever and acute dyspnoea. She developed cardiac tamponade due to pyopericardium with

Topics: Acute Disease; Aged; Anti-Bacterial Agents; Cardiac Tamponade; Disease Progression; Drainage; Female; Humans; Penicillanic Acid; Pericardial Effusion; Pericarditis, Constrictive; Piperacillin; Piperacillin, Tazobactam Drug Combination; Purpura, Thrombocytopenic, Idiopathic; Staphylococcal Infections; Staphylococcus aureus; Tomography, X-Ray Computed; Vancomycin

Hemophagoytic lymphohistiocytosis (HLH) is a rare life-threatening disorder caused by overactivation of the immune system, associated with infections, autoimmune disorders, and malignancies. The pathological hallmark of HLH is phagocytosis of blood cells and platelets by activated macrophages and histiocytes. In this report, we describe the onset of HLH in three children, aged 2, 5 and 7 years old, during the treatment of acute focal bacterial nephritis (AFBN) with an antibiotic, piperacillin-tazobactam (PIPC-TAZ). AFBN is acute localized bacterial infection of the kidney without abscess formation. PIPC-TAZ was chosen for the treatment of AFBN, because it not only has indications for complicated urinary tract infections, but also covers most of the causative bacteria of urinary tract infections, including β-lactamase-producing Escherichia coli. The clinical courses of the three patients were similar, and they were treated with PIPC-TAZ and amikacin (AMK) for AFBN. Fever went down 2 to 5 days later, and AMK was discontinued by day 6. However, fever recurred on 13 to 15 days after introduction of PIPC-TAZ therapy, even though all of the patients had no signs of recurrence of AFBN. The clinical features and laboratory tests of two patients fulfilled the criteria of HLH, whereas the other patient had initiated therapy before fulfilling the criteria. Cessation of PIPC-TAZ combined with corticosteroid therapy improved clinical symptoms. HLH of our patients was probably induced by PIPC-TAZ, as judged by the timing of the onset of HLH and the positivity of the drug-lymphocyte stimulation test. In conclusion, prolonged antibiotic therapy with PIPC-TAZ could be a cause of HLH.

Topics: Acute Disease; Bone Marrow; Child; Child, Preschool; Female; Humans; Lymphohistiocytosis, Hemophagocytic; Male; Nephritis; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Tomography, X-Ray Computed

The bacterium Raoultella planticola (R planticola) is a rare pathogen in humans. We report a case of mild acute pancreatitis (MAP) of biliary origin with cholangitis and bacteremia with R planticola in association with pancreatic panniculitis (PP). We present the case report of a 55-year-old woman.

Topics: Acute Disease; Anti-Bacterial Agents; Bacteremia; Cholangitis; Enterobacteriaceae; Female; Humans; Magnetic Resonance Imaging; Middle Aged; Pancreatitis, Acute Necrotizing; Panniculitis; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination

Nonoperative treatment of acute appendicitis appears to be feasible in adults. It is unclear whether the same is true for children.. Children 5-18 years with <48 h symptoms of acute appendicitis were offered nonoperative treatment: 2 doses of piperacillin IV, then ampicillin/clavulanate ×1 week. Treatment failure (worsening on therapy) and recurrence (after completion of therapy) were noted. Patients who declined enrollment were asked to participate as controls. Cost-utility analysis was performed using Pediatric Quality of Life Scale (PedsQL®) to calculate quality-adjusted life month (QALM) for study and control patients.. Twenty-four patients agreed to undergo nonoperative management, and 50 acted as controls. At a mean follow-up of 14 months, three of the 24 failed on therapy, and 2/21 returned with recurrent appendicitis at 43 and 52 days, respectively. Two patients elected to undergo an interval appendectomy despite absence of symptoms. Appendectomy-free rate at one year was therefore 71% (C.I. 50-87%). No patient developed perforation or other complications. Cost-utility analysis shows a 0.007-0.03 QALM increase and a $1359 savings from $4130 to $2771 per nonoperatively treated patient.. Despite occasional late recurrences, antibiotic-only treatment of early appendicitis in children is feasible, safe, cost-effective and is experienced more favorably by patients and parents.

Topics: Acute Disease; Adolescent; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Appendectomy; Appendicitis; beta-Lactamase Inhibitors; Child; Child, Preschool; Cost-Benefit Analysis; Drug Therapy, Combination; Feasibility Studies; Female; Humans; Male; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Quality of Life; Recurrence; Treatment Failure

Expanding antimicrobial resistance patterns in the face of stagnant growth in novel antibiotic production underscores the importance of antibiotic stewardship in which de-escalation remains an integral component. We measured the frequency of antibiotic de-escalation in a tertiary care medical center with an established antimicrobial stewardship program to provide a plausible benchmark for de-escalation.. A retrospective, observational study was performed by review of randomly selected electronic medical records of 240 patients who received simultaneous piperacillin/tazobactam and vancomycin from January to December 2011 at an 885-bed tertiary care medical center. Patient characteristics including antibiotic regimen, duration and indication, culture results, length of stay, and hospital mortality were evaluated. Antibiotic de-escalation was defined as the use of narrower spectrum antibiotics or the discontinuation of antibiotics after initiation of piperacillin/tazobactam and vancomycin therapy. Subjects dying within 72 h of antibiotic initiation were considered not de-escalated for subsequent analysis and were subtracted from the study population in determining a modified mortality rate.. The most commonly documented indications for piperacillin/tazobactam and vancomycin therapy were pneumonia and sepsis. Of the 240 patients studied, 151 (63%) had their antibiotic regimens de-escalated by 72 h. The proportion of patients de-escalated by 96 h with positive vs. negative cultures was similar, 71 and 72%, respectively. Median length of stay was 4 days shorter in de-escalated patients, and the difference in adjusted mortality was not significant (p = 0.82).. The empiric antibiotic regimens of approximately two-thirds of patients were de-escalated by 72 h in an institution with a well-established antimicrobial stewardship program. While this study provides one plausible benchmark for antibiotic de-escalation, further studies, including evaluations of antibiotic appropriateness and patient outcomes, are needed to inform decisions on potential benchmarks for antibiotic de-escalation.

Topics: Acute Disease; Aged; Anti-Bacterial Agents; Drug Resistance, Bacterial; Drug Therapy, Combination; Female; Hospital Mortality; Humans; Length of Stay; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia; Retrospective Studies; Sepsis; Vancomycin

Topics: Acute Disease; Anti-Bacterial Agents; Catheterization, Central Venous; Diagnosis, Differential; Drug Administration Routes; Escherichia coli; Fatigue; Female; Flank Pain; Fluid Therapy; Humans; Levofloxacin; Microbial Sensitivity Tests; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pyelonephritis; Systemic Inflammatory Response Syndrome; Tomography, X-Ray Computed; Treatment Outcome

Topics: Acute Disease; Anti-Bacterial Agents; Drug Interactions; Drug Therapy, Combination; Humans; Male; Meropenem; Middle Aged; Nephritis, Interstitial; Osteomyelitis; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Thienamycins

Abdominal actinomycosis in children is a rare disease, which is occasionally found on histologic examination after an operation for acute appendicitis. Because of its nonspecific clinical and radiological signs and symptoms and low prevalence, the diagnosis is hardly ever made before the patient undergoes an operation and tissue is available for pathologic evaluation. When the diagnosis is made, the patient should be treated with the appropriate long-term antibiotics. With antibiotic therapy, the prognosis is favorable. We describe a 13-year-old girl who presented with acute appendicitis and was found to have abdominal actinomycosis after undergoing open appendectomy, which was treated successfully with penicillin and piperacillin-tazobactam.

Topics: Actinomycosis; Acute Disease; Adolescent; Anti-Bacterial Agents; Appendectomy; Appendicitis; Cecal Diseases; Female; Humans; Penicillanic Acid; Penicillins; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prognosis; Treatment Outcome

Topics: Acute Disease; Adult; Anti-Bacterial Agents; Anti-Inflammatory Agents; Humans; Hydrocortisone; Male; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Streptococcal Infections; Streptococcus agalactiae; Tonsillitis

A case of central venous catheter-related bacteraemia due to Roseomonas mucosa in a neutropenic patient with acute myelogenous leukaemia is reported. The patient was successfully treated with amikacin and piperacillin-tazobactam. The clinical isolate was identified as R. mucosa by 16S rRNA gene sequencing.

Topics: Acute Disease; Adult; Amikacin; Anti-Bacterial Agents; Antimetabolites, Antineoplastic; Antineoplastic Agents; Bacteremia; Base Sequence; Catheterization, Central Venous; Cytarabine; Humans; Leukemia, Myeloid; Male; Methylobacteriaceae; Molecular Sequence Data; Neutropenia; Penicillanic Acid; Phylogeny; Piperacillin; Piperacillin, Tazobactam Drug Combination; RNA, Bacterial; RNA, Ribosomal, 16S; Vidarabine

Topics: Acute Disease; Aged; Anti-Bacterial Agents; Drug Eruptions; Exanthema; Female; Humans; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Skin Diseases, Vesiculobullous