cilastatin--imipenem-drug-combination and Pneumonia

This study aimed to investigate the efficiency of imipenem to prevent infectious complications in predicted severe acute pancreatitis (AP).. Consecutive AP patients were randomized to imipenem 3 × 500 mg intravenously daily or an identical placebo. Exclusion criteria were prior AP, chronic pancreatitis, active malignancy, immune deficiency, active infection, concomitant antibiotic treatment, pregnancy, and patients younger than 18 years. Infectious complications including infected pancreatic necrosis, pneumonia, urinary tract infection, positive blood cultures, sepsis, and other infections were assessed as the primary outcome. Secondary outcomes included mortality, persistent organ failure, systemic inflammatory response syndrome, local complications, serious adverse events, and need for surgical intervention.. Forty-nine patients were randomized to each group. Infectious complications were present in 10 versus 12 of 49 patients (relative risk [RR], 0.833; 95% confidence interval [CI], 0.398-1.747). There were no significant differences in infected pancreatic necrosis (RR, 1.5; 95% CI, 0.262-8.588), pneumonia (RR, 1.5; 95% CI, 0.262-8.588), urinary tract infection (RR, 0.6; 95% CI, 0.152-2.374), positive blood cultures (RR, 0.5; 95% CI, 0.047-5.336), sepsis (RR, 0.333; 95% CI, 0.036-3.095), and other (RR, 1.333; 95% CI, 0.315-5.648). We found no significant differences in secondary outcomes.. Concordantly to available evidence, there is currently no ground to support prophylactic use of antibiotics in predicted severe AP.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Antibiotic Prophylaxis; Bacterial Infections; Cilastatin, Imipenem Drug Combination; Double-Blind Method; Female; Humans; Male; Middle Aged; Outcome Assessment, Health Care; Pancreatitis; Pneumonia; Prospective Studies; Sepsis; Urinary Tract Infections

In a previous phase 3 study, the cure rates that occurred in patients with hospital-acquired pneumonia treated with tigecycline at the approved dose were lower than those seen with patients treated with imipenem and cilastatin (imipenem/cilastatin). We hypothesized that a higher dose of tigecycline is necessary in patients with hospital-acquired pneumonia. This phase 2 study compared the safety and efficacy of two higher doses of tigecycline with imipenem/cilastatin in subjects with hospital-acquired pneumonia. Subjects with hospital-acquired pneumonia were randomized to receive one of two doses of tigecycline (150 mg followed by 75 mg every 12 h or 200 mg followed by 100 mg every 12 h) or 1 g of imipenem/cilastatin every 8 h. Empirical adjunctive therapy was administered for initial coverage of methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa infection, depending on the randomization regimen. Clinical response, defined as cure, failure of treatment, or indeterminate outcome, was assessed 10 to 21 days after the last day of therapy. In the clinically evaluable population, clinical cure with tigecycline 100 mg (17/20, 85.0%) was numerically higher than with tigecycline 75 mg (16/23, 69.6%) and imipenem/cilastatin (18/24, 75.0%). No new safety signals with the high-dose tigecycline were identified. A numerically higher clinical response was observed with the 100-mg dose of tigecycline. This supports our hypothesis that a higher area under the concentration-time curve over 24 h in the steady state divided by the MIC (AUC/MIC ratio) may be necessary to achieve clinical cure in patients with hospital-acquired pneumonia. Further studies are necessary. (The ClinicalTrials.gov identifier for this clinical trial is NCT00707239.).

Topics: Adult; Aged; Anti-Bacterial Agents; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Female; Humans; Imipenem; Male; Middle Aged; Minocycline; Pneumonia; Tigecycline

To compare efficacy and safety of a tigecycline regimen with an imipenem/cilastatin regimen in hospital-acquired pneumonia patients, a phase 3, multicenter, randomized, double-blind, study evaluated 945 patients. Coprimary end points were clinical response in clinically evaluable (CE) and clinical modified intent-to-treat (c-mITT) populations at test-of-cure. Cure rates were 67.9% for tigecycline and 78.2% for imipenem (CE patients) and 62.7% and 67.6% (c-mITT patients), respectively. A statistical interaction occurred between ventilator-associated pneumonia (VAP) and non-VAP subgroups, with significantly lower cure rates in tigecycline VAP patients compared to imipenem; in non-VAP patients, tigecycline was noninferior to imipenem. Overall mortality did not differ between the tigecycline (14.1%) and imipenem regimens (12.2%), although more deaths occurred in VAP patients treated with tigecycline than imipenem. Overall, the tigecycline regimen was noninferior to the imipenem/cilastatin regimen for the c-mITT but not the CE population; this difference appears to have been driven by results in VAP patients.

Topics: Anti-Bacterial Agents; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Cross Infection; Double-Blind Method; Drug Combinations; Hospital Mortality; Humans; Imipenem; Microbial Sensitivity Tests; Minocycline; Pneumonia; Pneumonia, Ventilator-Associated; Tigecycline; Treatment Outcome

Nosocomial pneumonia and acute peritonitis may be caused by a wide array of pathogens, and combination therapy is often recommended. We have previously shown that imipenem-cilastatin monotherapy was as efficacious as the combination of imipenem-cilastatin plus netilmicin in these two settings. The efficacy of imipenem-cilastatin is now compared to that of piperacillin-tazobactam as monotherapy in patients with nosocomial pneumonia or acute peritonitis. Three hundred seventy one patients with nosocomial pneumonia or peritonitis were randomly assigned to receive either imipenem-cilastatin (0.5 g four times a day) or piperacillin-tazobactam (4.5 g three times a day). Three hundred thirteen were assessable (154 with nosocomial pneumonia and 159 with peritonitis). For nosocomial pneumonia, clinical-failure rates in the piperacillin-tazobactam group (13 of 75 [17%]) and in the imipenem-cilastatin group (23 of 79 [29%]) were similar (P = 0.09), as were the numbers of deaths due to infection (6 in the imipenem-cilastatin group [8%], 7 in the piperacillin-tazobactam group [9%]) (P = 0.78). For acute peritonitis, clinical success rates were comparable (piperacillin-tazobactam, 72 of 76 [95%]; imipenem-cilastatin, 77 of 83 [93%]). For infections due to Pseudomonas aeruginosa, 45 patients had nosocomial pneumonia (21 in the piperacillin-tazobactam group and 24 in the imipenem-cilastatin group) and 10 had peritonitis (5 in each group). In the patients with nosocomial pneumonia, clinical failure was less frequent in the piperacillin-tazobactam group (2 of 21 [10%]) than in the imipenem-cilastatin [corrected] group (12 of 24 [50%]) (P = 0.004). Bacterial resistance to allocated regimen was the main cause of clinical failure (1 in the piperacillin-tazobactam group and 12 in the imipenem-cilastatin group). For the patients with peritonitis, no difference in clinical outcome was observed (five of five cured in each group). The overall frequencies of adverse events related to treatment in the two groups were similar (24 in the piperacillin-tazobactam group, 22 in the imipenem-cilastatin group). Diarrhea was significantly more frequent in the piperacillin-tazobactam group (10 of 24) than in the imipenem-cilastatin group (2 of 22). This study suggests that piperacillin-tazobactam monotherapy is at least as effective and safe as imipenem-cilastatin monotherapy in the treatment of nosocomial pneumonia or peritonitis. In P. aeruginosa pneumonia, piperacillin-tazobactam achieved

Topics: Acute Disease; Adult; Aged; Cilastatin; Cilastatin, Imipenem Drug Combination; Cross Infection; Drug Combinations; Drug Therapy, Combination; Female; Humans; Imipenem; Male; Middle Aged; Penicillanic Acid; Peritonitis; Piperacillin; Pneumonia; Prospective Studies; Pseudomonas Infections; Tazobactam

Topics: Aged; Anti-Infective Agents; APACHE; Cilastatin; Cilastatin, Imipenem Drug Combination; Ciprofloxacin; Double-Blind Method; Drug Combinations; Drug Therapy, Combination; Female; Hospitalization; Humans; Imipenem; Male; Middle Aged; Pneumonia; Prospective Studies

Intravenously administered ciprofloxacin was compared with imipenem for the treatment of severe pneumonia. In this prospective, randomized, double-blind, multicenter trial, which included an intent-to-treat analysis, a total of 405 patients with severe pneumonia were enrolled. The mean APACHE II score was 17.6, 79% of the patients required mechanical ventilation, and 78% had nosocomial pneumonia. A subgroup of 205 patients (98 ciprofloxacin-treated patients and 107 imipenem-treated patients) were evaluable for the major efficacy endpoints. Patients were randomized to receive intravenous treatment with either ciprofloxacin (400 mg every 8 h) or imipenem (1,000 mg every 8 h), and doses were adjusted for renal function. The primary and secondary efficacy endpoints were bacteriological and clinical responses at 3 to 7 days after completion of therapy. Ciprofloxacin-treated patients had a higher bacteriological eradication rate than did imipenem-treated patients (69 versus 59%; 95% confidence interval of -0.6%, 26.2%; P = 0.069) and also a significantly higher clinical response rate (69 versus 56%; 95% confidence interval of 3.5%, 28.5%; P = 0.021). The greatest difference between ciprofloxacin and imipenem was in eradication of members of the family Enterobacteriaceae (93 versus 65%; P = 0.009). Stepwise logistic regression analysis demonstrated the following factors to be associated with bacteriological eradication: absence of Pseudomonas aeruginosa (P < 0.01), higher weight (P < 0.01), a low APACHE II score (P = 0.03), and treatment with ciprofloxacin (P = 0.04). When P. aeruginosa was recovered from initial respiratory tract cultures, failure to achieve bacteriological eradication and development of resistance during therapy were common in both treatment groups (67 and 33% for ciprofloxacin and 59 and 53% for imipenem, respectively). Seizures were observed more frequently with imipenem than with ciprofloxacin (6 versus 1%; P = 0.028). These results demonstrate that in patients with severe pneumonia, monotherapy with ciprofloxacin is at least equivalent to monotherapy with imipenem in terms of bacteriological eradication and clinical response. For both treatment groups, the presence of P. aeruginosa had a negative impact on treatment success. Seizures were more common with imipenem than with ciprofloxacin. Monotherapy for severe pneumonia is a safe and effective initial strategy but may need to be modified if P. aeruginosa is suspected or recovered from pat

Topics: Adult; Aged; Anti-Bacterial Agents; Cilastatin; Cilastatin, Imipenem Drug Combination; Ciprofloxacin; Double-Blind Method; Drug Combinations; Drug Resistance, Microbial; Female; Hospitalization; Humans; Imipenem; Injections, Intravenous; Male; Middle Aged; Pneumonia; Pseudomonas aeruginosa; Pseudomonas Infections; Regression Analysis; Seizures

In four prospective randomized clinical trials between November 1983 and March 1988, we studied 270 patients with severe bacterial infections, mainly lower respiratory tract ones. We compared ciprofloxacin and imipenem/cilastatin in the first study, ciprofloxacin and ofloxacin in the second study, ciprofloxacin and ticarcillin/clavulanic acid in the third study, and ofloxacin and cefpirome in the fourth study. A total of 90 pneumonias, 139 LRTIs, 22 septicaemias and 19 other bacterial infections were treated; the dominant pathogens were Pseudomonas aeruginosa and enterobacteria. Clinical success rates were high; cure or improvement was registered in 89% of the patients on ciprofloxacin, 89% on ofloxacin and 85% on beta-lactams. Treatment failures occurred mainly in ICU patients with terminal underlying diseases. Bacteriologically, eradication rates were high for enterobacteria and Staphylococcus aureus, but a relatively high persistence rate was seen for P. aeruginosa due to increased resistance and/or specific type and location of the infections. The incidence of side-effects was relatively high (23%-29%) which was related to careful monitoring. Adverse effects were group-specific (CNS reactions with quinolones, diarrhoea with beta-lactam antibiotics).

Topics: Cilastatin; Cilastatin, Imipenem Drug Combination; Ciprofloxacin; Clavulanic Acids; Drug Combinations; Drug Therapy, Combination; Humans; Imipenem; Ofloxacin; Pneumonia; Prospective Studies; Remission Induction; Respiratory Tract Infections; Sepsis; Ticarcillin

In February 2018, one 54-year-old male patient with severe scald complicated with pneumonia and sepsis was transferred to Qingdao Municipal Hospital from other hospital. Drugs including cephalosporin, vancomycin, and imipenem/cilastatin combined with ciprofloxacin were used successively for anti-infective treatment, with no obvious effect. Multiple bacterial culture results of sputum, blood, and wound exudate showed infection of extensively drug resistant. 2018年2月，青岛市市立医院收治1例经外院转入的严重烫伤合并肺炎和脓毒症的54岁男性患者。先后使用头孢菌素、万古霉素、亚胺培南/西司他丁＋环丙沙星等抗感染治疗，但无明显效果。痰液、血液及创面分泌物多次细菌培养结果提示泛耐药铜绿假单胞菌感染。入院第4天调整抗感染治疗方案，补充血浆、红细胞及白蛋白，行营养支持及对症处理，同时进行用药监护，关注药物相关不良反应。经过10余天的治疗，患者感染得到有效控制，病情逐渐好转。本病例提示，严重烧伤患者易发生严重且致命的全身性感染，抗菌药物的不规范使用增加了泛耐药菌的感染风险，清晰的抗感染思路和抗菌药物的有效应用有助于提高感染治疗的成功率，对改善严重烧伤患者的预后具有重要价值。.

Topics: Anti-Bacterial Agents; Burns; Cilastatin, Imipenem Drug Combination; Humans; Male; Middle Aged; Pneumonia; Pseudomonas aeruginosa; Sepsis

Male Wistar albino rats were allocated to three groups-sham operated (n: 10), splenectomized (n: 20) and splenic autotransplanted (n: 10). Twelve weeks after operation, all were challenged with 1.8 x 10(8) cfu/ml Pseudomonas aeruginosa intranasally. Half of the splenectomized rats received imipenem-cilastatin after 2 h of bacterial challenge. Mortality was then observed for the next 12 days. All animals were autopsied and liver, kidney, spleen and lung specimens were processed for microbiological culture and histopathological examination. In 80% of autotransplanted rats, splenic tissue regeneration was histopathologically verified. Hemoglobin oxidation of erythrocytes increased in splenectomized rats and remained close to control levels in the autotransplanted group. No significant difference was detected between IgM levels of splenectomized and autotransplanted groups. Mortality rates were the same for all groups, except that splenectomized animals given antimicrobial therapy had increased survival rates. In conclusion, it is likely that the spleen has no role in protection against pulmonary sepsis and that only appropriate antimicrobial therapy can protect the splenectomized host from Pseudomonas sepsis.

Topics: Animals; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Therapy, Combination; Hemoglobins; Imipenem; Immunoglobulin M; Lung; Male; Oxygen; Pneumonia; Pseudomonas aeruginosa; Pseudomonas Infections; Rats; Rats, Wistar; Sepsis; Spleen; Splenectomy; Transplantation, Autologous

Topics: Acute Disease; Adult; Aged; Bacterial Infections; Chronic Disease; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Female; Humans; Imipenem; Lung Diseases; Male; Microbial Sensitivity Tests; Middle Aged; Pneumonia; Pulmonary Disease, Chronic Obstructive; Safety

Calculated chemotherapy is based on the knowledge of the typical bacterial agents of a particular infection. From January 1983 to August 1985 bacteriological findings from surgical patients with peritonitis, septicemia or pneumonia treated in an intensive care unit were analysed. The study concentrated on those findings only which differed from previous bacteriological investigations. During the first three days 53 patients on assisted ventilation suffering from peritonitis exhibited mainly enterobacteria in their peritoneal secretions. At day 10 or later we also found bacteria from the pseudomonas group. At that time the bacterial spectrum of bronchial secretions was comparable to that of the peritoneal secretions of the same patient. After day 10, the bacterial spectrum was similar in 36 ventilated patients without peritonitis, in 56 patients suffering from post-operative pneumonia and in peritonitis patients. According to our findings, calculated chemotherapy may be based on the fact that patients with peritonitis who cannot be cured within a few days have a bacterial flora comparable to that of patients with septicemia or pneumonia. Patients with severe infections following surgery, such as potentially fatal pneumonia, generalised peritonitis or septicemia were treated with imipenem/cilastatin, according to the above definitions of calculated chemotherapy. 37 of 46 patients treated between May and December 1985, were clinically cured. Microorganisms persisted in five clinically cured patients. Development of resistance to imipenem was observed in one case. In one case treatment had to be stopped because of an allergic skin reaction. Monotherapy of peritonitis by imipenem/cilastatin appeared more satisfactory than treatment with combinations of other antibiotics.

Topics: Adult; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Cyclopropanes; Drug Combinations; Female; Humans; Imipenem; Male; Middle Aged; Peritonitis; Pneumonia; Postoperative Complications; Respiration, Artificial; Retrospective Studies; Sepsis; Thienamycins

Imipenem (N-Formimidoyl thienamycin) (MK-0787) is a new beta-lactam carbapenem antibiotic. When it is combined with the renal dipeptidase inhibitor cilastatin (MK-0791) the combination is known as primaxin. In this study 28 adult patients (24 males and 4 females) with acute bacterial pneumonia were treated with primaxin. Twenty-one patients were evaluable and 20 (95%) were clinically cured of their pneumonia. Bacteriological cures were demonstrated in 84% of the cases. One patient with a susceptible Pseudomonas aeruginosa failed. Major complications or toxic reactions included antibiotic associated diarrhoea in one patient; hypotension in one patient; increased grand mal seizures in one patient and elevated liver function studies in one patient. Results of this study suggest that primaxin will be useful in the treatment of a variety of serious Gram-positive and Gram-negative pneumonias. The true incidence of possible toxic reactions with this drug is not known at this time and awaits further experience.

Topics: Adult; Aged; Cilastatin; Cilastatin, Imipenem Drug Combination; Cyclopropanes; Dipeptidases; Drug Combinations; Drug Resistance, Microbial; Female; Humans; Imipenem; Male; Microbial Sensitivity Tests; Middle Aged; Pneumonia; Thienamycins