Satisfactory Clinical Response Rate Research Articles

Can carboplatin or etoposide replace actinomycin-d for second-line treatment of methotrexate resistant low-risk gestational trophoblastic neoplasia?

ObjectiveTo evaluate the impact of periodic shortage of actinomycin-d (Act-d) in the treatment of Brazilian patients with low-risk gestational trophoblastic neoplasia (GTN) after methotrexate and folinic acid rescue (MTX/FA) resistance, treated alternately with carboplatin or etoposide as a second-line regimen. MethodsRetrospective cohort that included patients with failure of first-line MTX/FA regimen for low-risk GTN treated at Rio de Janeiro Federal University, Universidade Federal de São Paulo and Irmandade da Santa Casa de Misericórdia de Porto Alegre, from January/2010- December/2017. ResultsFrom 356 patients with low-risk GTN treated with MTX/FA, 75 (21.1%) developed resistance, of which 40 (53.3%) received Act-d, 23 (30.7%) carboplatin and 7 (9.3%) etoposide. Although patients treated with single-agent chemotherapy as a second-line regimen had comparable clinical and primary treatment characteristics, those treated with Act-d (80%, p = 0.033) or etoposide (71.4%, p = 0.025) had higher remission rates when compared with carboplatin (47.8%). Only 29% of patients treated with carboplatin received the chemotherapy cycles without delay compared to Act-d (98%, p < 0.001) or etoposide (85%, p = 0.009). Patients treated with carboplatin had significantly more hematological toxicity, notably anemia (30.4%, p = 0.008), lymphopenia (47.7%, p < 0.001) and thrombocytopenia (43.4%, p < 0.001), as well as a higher occurrence of febrile neutropenia (14.4%, p = 0.044) and vomiting (60%, p < 0.001) than those receiving Act-d (5%, none, 2.5%, none, 10%, respectively). ConclusionCarboplatin did not have a satisfactory clinical response rate, likely due to severe hematological toxicity, which postponed chemotherapy. Our results reinforce the preference for Act-d as a second-line agent in patients with low-risk GTN after MTX/FA resistance.

Voriconazole Treatment of Invasive Aspergillosis

The objective of this study was to assess, in a real-world setting, the predictive validity (in terms of clinical outcome and treatment cost) of the voriconazole arm of a health-economic model applied in the Belgian reimbursement submission for use of voriconazole in the treatment of invasive aspergillosis. A non-interventional study was designed to prospectively collect clinical response and direct costs data related to the treatment of invasive aspergillosis with voriconazole (oral, intravenous) in real-world practice. The outcomes of this study were compared with the inputs and outputs of the health-economic model. For the analysis, unit costs of 2002 from the public payer's perspective, as used in the model, were applied. Data from 116 patients with invasive aspergillosis starting treatment with voriconazole were collected. At 12 weeks, there were similar rates of satisfactory clinical response for the observational study and the model, the latter based on the results of a clinical study (50% vs 53%, respectively). Overall mortality rates at 84 days were 42% in the observational study and 29% in the model. Average total healthcare cost associated with voriconazole treatment was lower in the observational study compared with the model for all patients. When the cost for all hospitalization days from the start until the end of the fungal infection was included in the analysis, the average total cost was euro19,674. When the cost for only those hospitalization days solely related to the fungal infection was included in the analysis, the average total cost was euro12,376. These costs are below the cost predicted by the model of euro21,298. This analysis demonstrates that the results provided in the voriconazole arm of the health-economic model were valid estimates with regard to real-world outcomes but with a slightly better survival rate and higher costs than in real life.

A post hoc subgroup analysis of meropenem versus imipenem/cilastatin in a multicenter, double-blind, randomized study of complicated skin and skin-structure infections in patients with diabetes mellitus

Background:In a multicenter, international, double-blind, randomized clinical trial involving hospitalized patients with complicated skin and skin-structure infections (cSSSIs), meropenem and imipenem/cilastatin (both administered 500 mg intravenously every 8 hours) were not significantly different in their efficacy and safety profiles. Objective:The objective of the post hoc subgroup analysis discussed in the current article was to report the efficacy and tolerability of meropenem and imipenem/cilastatin for the treatment of cSSSIs in patients with or without underlying diabetes mellitus (DM). Methods:Hospitalized patients aged ≥13 years with evidence of cSSSIs were eligible for inclusion. Patients were randomized to receive meropenem or imipenem/cilastatin, each 500 mg intravenously every 8 hours, for at least 3 days and up to a maximum of 14 days. Patients were analyzed according to the presence or absence of DM and by the pathogen(s) isolated from wound cultures at baseline, end of N treatment, and test-of-cure visits. The primary efficacy end point was clinical outcome at the posttreatment follow-up (test-of-cure) visit in the clinically evaluable and modified intent-to-treat (intent-to-treat [ITT] subjects who met all eligibility criteria) populations; this was defined as 7 to 14 days after final administration of antibiotics. The secondary efficacy end points included clinical response at the test-of-cure visit in the ITT population (ie, those who received >1 dose of study drug) and at the end of N treatment visit in the clinically evaluable and fully evaluable populations. At baseline, the end of N treatment, and the test-of-cure visits, specimens were obtained from the most extensive site of skin and skin-structure infection and were cultured for bacteria. Adverse events were monitored daily during treatment and for 30 days after the completion of all antibiotic treatment. Results:Of the 1076 patients enrolled in the original study, 398 had DM. The mean ages of patients with and without DM were 55 and 45 years, respectively; 17.3% of patients with DM and 6.1% of patients without DM had impaired renal function at study entry. Complex abscess was the most common infection diagnosis in both groups (patients with DM, 30.0%; patients without DM, 48.8%). The other top infections per group (patients with and without DM, respectively) were as follows: cellulitis, 24.6% and 12.4%; and ischemic/diabetic ulcers, 20.9% and 1.9%. Gram-negative aerobic and anaerobic pathogens accounted for >40% of bacterial isolates from both groups, with polymicrobial infections reported in 44.2% of patients with DM and 34.0% of patients without DM. In the clinically evaluable population, the satisfactory clinical response rate was 85.6% for patients with DM receiving meropenem and 72.4% for those receiving imipenem/cilastatin; for patients without DM, those rates were 86.6% and 89.0%, respectively. Meropenem and imipenem/cilastatin were generally well tolerated. Reported adverse events were similar between groups. Conclusion:This subgroup analysis found that 500 mg every 8 hours intravenously of meropenem or imipenem/cilastatin appeared efficacious and well tolerated for the treatment of cSSSIs among these patients with and without DM.

Meropenem versus imipenem/cilastatin as empirical monotherapy for serious bacterial infections in the intensive care unit

To compare the efficacy and tolerability of meropenem and imipenem/cilastatin as empirical monotherapy in intensive care unit (ICU) patients with serious bacterial infections. A multicenter, open-label, randomized, parallel-group trial was conducted in Belgium, evaluating empirical monotherapy with meropenem or imipenem/cilastatin (both 1 g/8 h intravenously) in ICU patients with one or more of the following infections caused by sensitive pathogens: lower respiratory tract infection (LRTI) in ventilated patients, intra-abdominal infection or sepsis. The overall satisfactory clinical response rate at the end of randomized treatment was 77.0% (67/87) with meropenem and 68.1% (62/91) with imipenem/cilastatin (difference 8.9%; 95% confidence interval -4.2% to 21.9%; P = 0.185). The two drugs produced similar satisfactory clinical response rates against LRTIs: 68.3% (41/60) with meropenem versus 68.6% (35/51) with imipenem/cilastatin. Meropenem appeared to be slightly more effective against intra-abdominal infections: 95.5% (21/22) versus 76.7% (23/30), respectively. All five meropenem recipients with sepsis had a satisfactory clinical response, compared to 40.0% (4/10) of those who received imipenem/cilastatin. The overall satisfactory bacteriologic response rate was 67.1% (49/73) with meropenem and 60.3% (44/73) with imipenem/cilastatin (difference 6.9%; 95% confidence interval -8.7% to 22.4%; P = 0.389). The predominant pathogens were Escherichia coli, Enterobacter spp. and Pseudomonas aeruginosa. No incidences of drug-related nausea and vomiting were reported, but one probable drug-related seizure occurred in the imipenem/cilastatin group. Meropenem is at least as efficacious (clinically and bacteriologically) as imipenem/cilastatin for the empirical monotherapy of serious bacterial infections in ICU patients, and it can therefore be considered a useful option in this setting. Moreover, meropenem is well tolerated and offers several potential advantages, including greater in vitro activity against Gram-negative pathogens and the option of bolus administration.

Meropenem: clinical response in relation to in vitro susceptibility

To collate the clinical response and pathogen eradication rates for meropenem monotherapy with in vitro susceptibility of the causative pathogens. Data were compiled from 17 randomized clinical studies that compared meropenem monotherapy with standard treatment options, often combinations. A total of 4906 pathogens from lower respiratory tract, intra-abdominal, obstetric/gynecological, skin/soft tissue, meningitis, or pediatric infections were assessed. Of these, 3713 pathogens (1963 meropenem, 1750 comparators) were evaluable. The overall rates of satisfactory clinical response (cure or improvement) and pathogen eradication (eradication or presumed eradication) at the end of therapy were similar with meropenem (93% for both responses) and the comparators (92%), as were the rates in each infection type. For each pathogen, the clinical response and eradication rates with meropenem were similar across the minimum inhibitory concentration (MIC) range of < or = 0.25 to 4 mg/L. Overall, a satisfactory clinical response occurred in 93% (1580 of 1708) of infections caused by nonfastidious pathogens with MICs < or = 4 mg/L and in 84% (16 of 19) of those with an MIC of 8 mg/L. Pathogen eradication rates were similar (93 and 79%, respectively). A similar profile was observed for fastidious pathogens. The high rates of satisfactory clinical response and pathogen eradication produced by meropenem in each type of infection were generally independent of the causative pathogen, whether Gram-positive or -negative aerobe or anaerobe or when occurring as mono- or polymicrobial infections. The attractive in vitro profile of meropenem translates into good clinical efficacy. The National Committee for Clinical Laboratory Standards has now defined meropenem MIC breakpoints for nonfastidious aerobes or anaerobes as < or = 4 (susceptible), 8 (intermediate) and > or = 16 mg/L (resistant), respectively. The susceptibility breakpoint for Streptococcus spp. (excluding Streptococcus pneumoniae) is < or = 0.5 mg/L and, since meropenem is indicated for the treatment of meningitis, the susceptibility breakpoint for S. pneumoniae and Haemophilus influenzae is < or = 0.25 and < or = 0.5 mg/L, respectively. Meropenem monotherapy is therefore a valid option for the initial empirical treatment of a range of serious infections caused by single or multiple bacterial pathogens.

Efficacy and safety of cefepime treatment in Chinese patients with severe bacterial infections: in comparison with ceftazidime treatment

An open label, randomized comparative study was conducted to evaluate the safety and efficacy of cefepime, in comparison with ceftazidime, in the treatment of adult hospitalized Chinese patients with severe bacterial infections. Forty patients with severe infections including septicemia, urinary tract infection and bacterial pneumonia were randomly assigned to receive treatment with cefepime (2 g intravenously every 12 h) or ceftazidime (2 g intravenously every 8 h). The cefepime group (20 evaluable patients) and ceftazidime group (16 evaluable patients) were comparable with respect to age, sex, underlying diseases and distribution of infection type. In both groups urinary tract infection was the most common type of infection and Escherichia coli was the most common etiologic microorganism. The rates of satisfactory clinical response were similar in the cefepime and ceftazidime groups (95 versus 93.7%; 95% confidence interval: −0.14∼0.17, P=0.87). The bacteriological response rates of the cefepime and ceftazidime groups did not differ significantly (88.9 versus 85.7%; 95% confidence interval: −0.30∼0.36, P=0.85). Both cefepime and ceftazidime were well tolerated, with similar incidence of side effects. The results of this study suggest that cefepime is as safe and effective as ceftazidime for the treatment of serious infections in adult hospitalized Chinese patients.

Pneumonia: The Impact of Risk Factors on the Outcome of Treatment with Meropenem and Ceftazidime

This analysis comprises data pooled from two clinical trials of meropenem (0.5 g 8-hourly) versus ceftazidime (1 g 8-hourly) in hospitalized patients with community-acquired pneumonia. The clinical and bacteriological responses to treatment were assessed in relation to a range of risk factors previously linked to a poor clinical outcome. 393 patients (198 meropenem, 195 ceftazidime) were clinically evaluable while 230 (113 meropenem, 117 ceftazidime) were bacteriologically evaluable. Meropenem was highly effective, independent of associated risk factors, producing overall satisfactory clinical and bacteriological response rates at the end of therapy of 91.4% and 94.7%, respectively, similar to those produced by ceftazidime (90.3% and 92.3%, respectively). Clinical and bacteriological treatment outcome were similar in patients with up to three of the following key risk factors: age >65 years, male gender, serum urea >7 mmol/L, serum albumin <35 g/L and difficult-to-treat pathogens. Meropenem also achieved high clinical (85.7%) and bacteriological (89.3%) success rates in patients requiring ventilation, as did ceftazidime (81.6% and 87.1%, respectively). Both agents were highly effective against both Gram-negative and Gram-positive causative pathogens, including those organisms normally considered difficult to treat and typical of nosocomial pneumonia (e.g. Enterobacteriaceae, Staphylococcus aureus, Pseudomonas aeruginosa). Thus, meropenem and ceftazidime were highly effective in patients hospitalized with community-acquired pneumonia, irrespective of a number of concurrent risk factors (including those regarded as key risk factors). Furthermore, the analysis points to a role for meropenem 0.5 g 8-hourly in the treatment of nosocomial pneumonias that do not require intensive care unit admission and/or mechanical ventilation. Overall, this novel analysis of trial data suggests that incorporation of key risk factor endpoints into the initial design of pneumonia studies may prove to be a useful approach in defining appropriate antibiotic treatment for specific patient groups.

A comparative study of meropenem and ceftazidime in the treatment of patients hospitalized with community-acquired pneumonia

This multicenter, open-label, randomized clinical trial compared the efficacy and tolerability of intravenous (IV) meropenem 0.5 g every 8 hours (n = 147) and IV ceftazidime 1 g every 8 hours (n = 148) as empiric monotherapy for 295 patients hospitalized with community-acquired pneumonia. Seventy-four meropenem recipients and 81 ceftazidime recipients with pneumonia were assessable both clinically and bacteriologically. In these patients, no statistically significant differences were reported in the satisfactory clinical (95% with meropenem vs 90% with ceftazidime) or bacteriologic (95% with meropenem vs 93% with ceftazidime) response rates with the two agents at the end of treatment. High satisfactory clinical (95% with meropenem vs 92% with ceftazidime) and bacteriologic (97% with meropenem vs 89% with ceftazidime) response rates were maintained at follow-up (2 to 4 weeks later). In 90 patients who were clinically assessable but bacteriologically unassessable (no pretreatment pathogen isolated), both agents produced a satisfactory clinical response rate of 87% at the end of therapy. Streptococcus pneumoniae was the most frequently isolated pretreatment pathogen (28%), but nosocomial-type pathogens such as Escherichia coli (5%), Pseudomonas aeruginosa (11%), and Klebsiella pneumoniae (6%) were also frequently isolated. Both medications were well tolerated, and the types of treatment-related adverse events were similar in the two treatment groups. These findings indicate that meropenem 0.5 g every 8 hours is a useful option for the empiric treatment of patients hospitalized with community-acquired pneumonia.

Cefepime Versus Ceftazidime in the Treatment of Lower Respiratory Tract Infections

The objective of the study was to compare the safety and efficacy of cefepime and ceftazidime in the treatment of community acquired lower respiratory tract infections of moderate intensity. Eighty-six patients were randomized at a 2:1 ratio to receive respectively cefepime 1 g b.i.d. or ceftazidime 1 g t.i.d. The drugs were well tolerated and the occurrence of adverse events in each group was comparable. The rates of satisfactory clinical response were 96% (49/51) for cefepime and 89% (24/27) for ceftazidime. A total of 73 pathogens were isolated and pathogen eradication rates were 98% and 96% respectively for the cefepime and ceftazidime treatment groups. In conclusion, the data confirmed that cefepime could be a good alternative to ceftazidime.

Meropenem. A review of its antibacterial activity, pharmacokinetic properties and clinical efficacy.

The parenteral carbapenem meropenem is relatively stable to inactivation by human renal dehydropeptidase (DHP-1) and does not require concomitant administration of a DHP-1 inhibitor such as cilastatin. It has a broad spectrum of antibacterial activity in vitro, the majority of Gram-negative, Gram-positive and anaerobic pathogens being highly susceptible to the drug. Meropenem has shown clinical and bacteriological efficacy in the treatment of a wide range of serious infections in adults and children which is at least comparable with that of currently available treatment options. Its clinical and bacteriological efficacy is similar to that of imipenem/cilastatin, clindamycin plus tobramycin and cefotaxime plus metronidazole in the treatment of intraabdominal infections; cefotaxime or ceftriaxone in the treatment of meningitis; imipenem/cilastatin, and ceftazidime with or without an aminoglycoside, in lower respiratory tract infections; and imipenem/cilastatin or ceftazidime in the treatment of urinary tract infections. Satisfactory clinical and bacteriological response rates have also been achieved in patients with skin and skin structure infections, obstetric and gynaecological infections or septicaemia, and in immunocompromised patients with febrile episodes. Preliminary findings also indicate efficacy in the treatment of respiratory tract infections in patients with cystic fibrosis. The tolerability profile of meropenem is generally similar to that of comparator agents, although it is associated with a lower incidence of adverse gastrointestinal effects (nausea and vomiting) than imipenem/cilastatin. Importantly, the incidence of seizures in patients with meningitis is not increased following administration of meropenem. Thus, meropenem is an effective broad spectrum antibacterial drug for the treatment of a wide range of infections including polymicrobial infections in both adults and children, with comparable efficacy to imipenem/cilastatin and various other treatment regimens. Meropenem is likely to be of greatest value as empiric monotherapy in the treatment of serious infections for those caused by multiply-resistant pathogens. Further clinical experience is necessary, however, to ultimately define its place in therapy.

Multi-investigator evaluation of the efficacy and safety of cefprozil, amoxicillin-clavulanate, cefixime and cefaclor in the treatment of acute otitis media

Cefprozil was evaluated in the treatment of acute otitis media with effusion in three open, randomized, multicenter comparative clinical trials. In two trials, 891 pediatric patients were enrolled to either cefprozil or amoxicillin-clavulanate dosage regimens. The treatment groups were comparable in demographic characteristics, and presented with otalgia, middle-ear effusion, or inflamed or bulging tympanic membrane on otoscopic examination. In all patients, tympanocentesis and a culture were required. Two cefprozil oral doses were evaluated, 30 mg/kg/day and 40 mg/kg/day divided into two equal doses (b.i.d.). Amoxicillin-clavulanate was administered at 40 mg/kg/day in three divided doses (t.i.d.). The recommended duration of therapy was ten days. The predominant bacteria isolated were Haemophilus influenzae and Moraxella catarrhalis. The overall satisfactory clinical response rates were similar for cefprozil (83%) and amoxicillin-clavulanate (81%). The bacteriological response rates did not differ significantly, at 84% and 82%. Cefprozil eradicated the most common pathogen, Streptococcus pneumoniae, more often at 91%, vs. 84% for amoxicillin-clavulanate. The eradication rates were similar against Haemophilus influenzae and Moraxella catarrhalis. The patients treated with cefprozil had a lower rate of adverse clinical events (11%) compared to those with amoxicillin-clavulanate (20%). More gastrointestinal adverse experiences, including diarrhea, were reported in the amoxicillin-clavulanate-treated patients. In Study 3, cefprozil 30 mg/kg/day (b.i.d.) was compared to cefaclor 40 mg/kg/day (t.i.d.) and cefixime 8 mg/kg/day (q.d) in the treatment of acute otitis media in 388 pediatric patients. The patients were treated for 10 days, with a follow-up of 18 days. The overall clinical cure rates were 85%, 89% and 85%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Cefotetan in the treatment of obstetric and gynecologic infections

The efficacy, tolerance, and safety of cefotetan—a new 7-α-methoxy cephalosporin—was assessed in controlled and uncontrolled evaluations involving 131 evaluable patients hospitalized with obstetric and gynecologic infections. The 99% satisfactory clinical response rate obtained with this drug was equivalent to that obtained with either moxalactam or cefoxitin, yet the mean amount of cefotetan given was lower than that of the other two drugs. Cefotetan was well tolerated and produced no major adverse reactions. In this era of Diagnosis Related Groups and cost containment, the twice-daily dosage schedule of cefotetan is a decided cost benefit.

Cefmenoxime Efficacy, Safety, and Pharmacokinetics in Critical Care Patients with Nosocomial Pneumonia

Nephrotoxicity frequently complicates the use of aminoglycosides in severely compromised acute care patients. Therefore, an open clinical trial was initiated to determine if cefmenoxime alone is useful in serious nosocomial pneumonias. Thirty consecutive patients were entered in the trial, and 28 patients with an average age of 66 years were evaluable. Most were malnourished at entry, with serum albumin averaging 2.8 g/dl and prognostic nutritional index values over 70 percent (normal less than 40 percent). One-half the patients had severe chronic obstructive pulmonary disease and 68 percent required ventilators. Fifty-seven percent had concomitant cardiac disease, and 79 percent had previously been treated with antibiotics. Pneumonia was proven to be present by new infiltrate on chest x-ray, new fever, elevated white blood cell count, and gram-negative rods on gram stain and in cultures of tracheal aspirates or sputum. Patients were given cefmenoxime 1 to 2 g every six hours an average of 12 days. Cefmenoxime peak (one hour) and trough concentrations were measured by high pressure liquid chromatography and averaged 58 and 7 micrograms ml, respectively. Pharmacokinetic data in 18 patients were determined from serum profiles. Gram-positive organisms, Escherichia coli, Klebsiella, and Hemophilus influenzae were usually eradicated. Persistence was noted for some Enterobacter, Pseudomonas, Serratia, and Acinetobacter. Persistence in patients with good clinical response was considered colonization rather than superinfection. Overall, a satisfactory clinical response rate was noted in 78.6 percent of evaluable patients, whereas four patients responded satisfactorily with recurrence and two treatments had an unsatisfactory response. No serious adverse effects were observed. Cefmenoxime is a promising agent in the treatment of susceptible pneumonias in critical care patients.

Cefmenoxime in the treatment of nosocomial pneumonias in critical care patients.

Nephrotoxicity frequently complicates the use of aminoglycosides in severely compromised acute care patients. Therefore, we initiated an open clinical trial to determine if cefmenoxime alone is useful for serious Gram-negative pneumonias in this population. Thirty consecutive patients were studied. Average age was 66 years. Most were malnourished at entry, with serum albumin averaging 2.8 g/dl and prognostic nutritional index values over 70% (normal less than 40%). One-half of the patients had severe COPD and 67.9% were on ventilators. Fifty-seven per cent suffered concomitant cardiac disease, and 78.6% had been previously treated with antibiotics. Pneumonia was proven by new infiltrates on chest X-ray, new fever, elevated WBC count and Gram-negative rods on Gram's stain and in cultures of tracheal aspirate or sputum. Patients were given cefmenoxime 1-2 g every 6 h for an average of 12 days. Cefmenoxime peak (1 h) and trough concentrations were measured by HPLC and averaged 58 and 7 mg/l respectively. Gram-positive organisms, Escherichia coli, Klebsiella spp. and Haemophilus influenzae were usually eradicated. Persistence was noted for Enterobacter, Pseudomonas and Acinetobacter spp. Persistence in patients with good clinical response was considered colonization rather than superinfection. Overall, satisfactory clinical response rate was noted in 78.6%, while four patients responded satisfactorily with recurrence, and two treatments were unsatisfactory. No serious adverse effects were observed. Cefmenoxime is a promising agent for treatment of susceptible pneumonias in critical care patients.

Estrogen receptors in mammary cancer: correlation with age, menopausal status, and response to therapy.

The concentration of estrogen receptor protein (ER) in 113 primary or metastatic breast cancers was studied. ER was found to be correlated with the age of the patient. The ER values were generally lower in premenopausal patients (5.6 fmol/mg cytosol protein) than in postmenopausal patients (32.8 fmol/mg cytosol protein). The ER values of perimenopausal patients (0-5 years since the last menstrual period) were heterogeneous but generally closer to those of the premenopausal patients. Use of the ER determination for allocation of the patients either to hormonal (tamoxifen or nandrolonedecanoate) or to cytostatic (adriamycin-cyclophosphamide or Cooper's regimen) therapy was shown to result in highly satisfactory clinical response rates (including complete and partial remissions and stabilized disease) of 68% and 67%, respectively. The practical limit of ER concentration for selection is between 3 and 10 fmol/mg cytosol protein in breast cancer.