sultamicillin and Pneumonia

Ceftriaxone (CTRX) and ampicillin/sulbactam (ABPC/SBT) are recommended by various guidelines as the first-line antibiotics for community-acquired pneumonia (CAP). However, which of these antibiotics is more effective for treating non-aspiration CAP remains unclear.. This study was a prospective, single-center, open-label, quasi-randomized controlled trial. Patients with adult CAP without risk for aspiration were allocated to either a CTRX or ABPC/SBT group based on the date of hospital admission. Macrolide was added to patients in each group. The primary outcome was the clinical response in the validated per-protocol (VPP) population at end of treatment (EOT). The secondary outcomes were clinical response during treatment and at end of study (EOS) in the VPP population, and mortality rate at day 30 in the modified intention-to-treat (MITT) population.. Of 696 screened patients, 433 patients were excluded and 263 patients were allocated to receive either of the treatments. Males comprised 54% of patients and mean age and PSI were 62.1 ± 19.8 years and 69.3 ± 30.0, respectively, with 124 patients allocated to the CTRX group and 138 patients allocated to the ABPC/SBT group. The clinical effectiveness rate for the VPP population at EOT was 90% in the CTRX and 96% in the ABPC/SBT group (p = 0.072, 95% confidence interval [CI] of risk difference [RD]: - 12.6-0.8%). No significant difference in effectiveness at day 4 was observed between the CTRX and ABPC/SBT groups (p = 0.079, 95%CI of RD: - 12.1-0.4%), but at day 7, ABPC/SBT was significantly more effective than CTRX in the VPP population (p = 0.047, 95%CI of RD: - 13.3--0.4%). No significant difference in late response at EOS was seen between CTRX and ABPC/SBT groups: cure (89 [86%] and 102 [94%]), relapse (5 [5%] and 1 [1%]) and failure (10 [10%] and 5 [5%]; p = 0.053). Deaths within 30 days in MITT population was higher in CTRX group (4 [3%]) than in ABPC/SBT group (0 [0%]) (p = 0.048, 95%CI of RD: 0.1-6.3%).. No significant difference in effectiveness was found between ABPC/SBT and CTRX at EOT. However, ABPC/SBT might be more effective in the early phase of treatment.. UMIN-CTR, UMIN000037464. Registered 25 July 2019 - Retrospectively registered, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000042262.

Topics: Adult; Aged; Aged, 80 and over; Ampicillin; Anti-Bacterial Agents; Ceftriaxone; Community-Acquired Infections; Drug Therapy, Combination; Female; Humans; Injections, Intravenous; Japan; Macrolides; Male; Middle Aged; Pneumonia; Prospective Studies; Risk Factors; Sulbactam

To evaluate if a 3-day ampicillin-sulbactam prophylaxis can reduce the occurrence of early-onset pneumonia (EOP) in comatose mechanically-ventilated patients.. This was a single-centre, prospective, randomised, open study.. A 10-bed general-neurological ICU in a 2,000-bed university hospital.. Comatose mechanically-ventilated patients with traumatic, surgical or medical brain injury.. Patients were randomized to either ampicillin-sulbactam prophylaxis (3 g every 6 h for 3 days) plus standard treatment or standard treatment alone.. Main outcome was the occurrence of EOP. Secondary outcome measures were occurrence of late-onset pneumonia, percentage of non-pulmonary infections and of emerging multiresistant bacteria, duration of mechanical ventilation and of ICU stay and ICU mortality. Interim analysis at 1 year demonstrated a statistically significant reduction of EOP in the ampicillin-sulbactam group, and the study was interrupted. Overall, 39.5% of the patients developed EOP, 57.9% in the standard treatment group and 21.0% in the ampicillin-sulbactam group (chi-square 5.3971; P =0.022). Relative risk reduction of EOP in patients receiving ampicillin-sulbactam prophylaxis was 64%; the number of patients to be treated to avoid one episode of EOP was three. No differences in other outcome parameters were found; however, the small sample size precluded a definite analysis.. Antibiotic prophylaxis with ampicillin-sulbactam significantly reduced the occurrence of EOP in critically ill comatose mechanically ventilated patients. This result should encourage a large multicenter trial to demonstrate whether ampicillin-sulbactam prophylaxis reduces patient mortality, and whether antibiotic resistance is increased in patients receiving prophylaxis.

Topics: Adult; Ampicillin; Antibiotic Prophylaxis; Brain Injuries; Cohort Studies; Coma; Critical Illness; Drug Resistance; Female; Humans; Italy; Male; Middle Aged; Pneumonia; Prospective Studies; Respiration, Artificial; Sulbactam

In a randomized prospective study ampicillin/sulbactam and cefamandole were compared in the therapy of patients hospitalized with community acquired pneumonia. Patients receiving ampicillin/sulbactam (n = 37) and cefamandole (n = 38) were similar with respect to age (mean age 70 vs. 76 years respectively), clinical characteristics, severity of illness and underlying disease. Pathogens isolated from patients in the cefamandole and ampicillin/sulbactam group, respectively, were Streptococcus pneumoniae (7 vs. 7 patients), Haemophilus parainfluenzae (7 vs. 6 patients), Haemophilus influenzae (5 vs. 5 patients), Staphylococcus aureus (5 vs. 4 patients), Escherichia coli (4 vs. 4 patients), Klebsiella pneumoniae (3 vs. 3 patients), Enterobacter spp. (2 vs. 3 patients), Moraxella catarrhalis (1 vs. 2 patients), and organisms of the oral flora (4 vs. 3 patients). The rate of resistance to penicillin was 80%, to clindamycin 76%, to erythromycin 45%, to ampicillin 43%, and to cefazolin 18%. Overall successful treatment rates of 81% for cefamandole and 97% for ampicillin/sulbactam (p = 0.05) were observed. Both cefamandole and ampicillin/sulbactam were shown to be effective agents for therapy of community acquired pneumonia; however ampicillin/sulbactam demonstrated superior overall clinical efficacy.

Topics: Adult; Aged; Aged, 80 and over; Ampicillin; Bacteria; Bacterial Infections; Cefamandole; Community-Acquired Infections; Female; Humans; Male; Middle Aged; Pneumonia; Prospective Studies; Sputum; Sulbactam

Clinical efficacy and safety of sultamicillin (SBTPC) in patients with lower respiratory tract infections, mainly pneumonia and bronchitis, have been evaluated in a multicenter trial by 19 institutions in the Kyushu area during a period of 12 months from December 1988 to November 1989. 1. Clinical evaluation was made in 132 patients and efficacy rates of SBTPC were 80.0% (28/35) for pneumonia, 78.5% (73/93) for bronchitis and 100% for the remaining 1 patient with other respiratory tract infections. The overall efficacy rate was 79.1% (102/129). 2. Clinical efficacy rate of SBTPC for respiratory tract infections in patients with underlying diseases such as chronic bronchitis, old pulmonary tuberculosis etc., was 75.0% (60/80) which was not significantly different from the efficacy rate of 85.7% (42/49) in patients without underlying diseases. 3. Of 13 patients who failed to respond to previous antibiotic treatments, 8 (61.5%) were effectively treated with SBTPC. 4. Clinical efficacy rates against infections caused by single species of organisms were 90.9% (10/11) for Haemophilus influenzae, 100% (8/8) for Streptococcus viridans and 100% (3/3) for Staphylococcus aureus. The overall clinical efficacy rate in all cases of monomicrobial infections was 88.6% (31/35), in polymicrobial infection 45.5% (5/11) and the overall efficacy rate in cases in which causative bacteria were identified was 78.3% (35/46). 5. Adverse reactions occurred in 6.8% (9/132) of the patients. The symptoms included allergic reaction in 1 patient, gastrointestinal system disorders in 7 patients and general fatigability in 1 patient. As abnormalities in laboratory test values, elevations of A1-P, GOT, and GPT were observed in 3 patients during the study, but returned to normal after discontinuation of SBTPC administration. 6. SBTPC is a useful antibiotic in the treatment of lower respiratory tract infections under the current medical environment where resistant organisms which produce beta-lactamases have been increasing.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Ampicillin; Bacterial Infections; Bronchitis; Drug Therapy, Combination; Female; Humans; Japan; Male; Middle Aged; Pneumonia; Respiratory Tract Infections; Sulbactam

Topics: Adult; Aged; Ampicillin; Clinical Trials as Topic; Double-Blind Method; Drug Combinations; Drug Evaluation; Female; Humans; Male; Middle Aged; Penicillanic Acid; Penicillin Resistance; Pneumonia; Respiratory Tract Infections; Sulbactam

Ampicillin-sulbactam is a first-line therapy for pneumonia and is mainly excreted by the kidney. It is important to optimize the dose and dosing interval of ampicillin-sulbactam because in patients with decreased renal function and low skeletal muscle mass, such as the elderly, excess drug may burden renal function. In this study, we evaluated indices of renal function and optimized the dose and dosing interval of ampicillin-sulbactam based on pharmacokinetics (PK) and pharmacodynamics theory in elderly patients. The serum concentrations of ampicillin and sulbactam were measured by HPLC, and PK parameters were calculated. Correlations between the clearance of ampicillin or sulbactam and renal function were evaluated, and dosing optimization was calculated based on PK parameters. The PK parameters of ampicillin were CL = 6.5 ± 4.0 L/h, Vd = 19.3 ± 0.2 L, Ke = 0.4 ± 0.2, and t

Topics: Aged; Aged, 80 and over; Aging; Ampicillin; Anti-Bacterial Agents; Cystatin C; Dose-Response Relationship, Drug; Drug Dosage Calculations; Female; Glomerular Filtration Rate; Humans; Kidney; Male; Models, Biological; Pneumonia; Renal Elimination; Sulbactam

Infections are a major cause for morbidity and mortality in liver transplant recipients. So far there has been no study systematically investigating the correlation between the MELD (Model for End-Stage Liver Disease) scoring system and complications caused by infections. The aim of the present retrospective study was to evaluate the impact of the pretransplant MELD score on incidence and mortality of pneumonia and septicemia in liver transplant recipients.. The clinical courses of 201 liver transplant recipients between 12/2006 and 3/2009 were recorded and analyzed on the basis of chart review. Patients were stratified into three groups (pretransplant MELD score: group I 6-20, group II ≥ 21-30, group III ≥ 31-40) and compared in terms of incidence of infection and survival.. The mean pretransplant MELD score was 22 ± 12. There were 81 patients in group I, 65 patients in group II, and 55 patients in group III. There was no difference in incidence of infections between the MELD groups. However, septicemia-associated mortality was significantly higher in group III.. A high MELD score is not associated with higher incidence of infections but it is associated with a significantly higher mortality in the case of septicemia. Prevention of infections is of utmost importance, especially in liver transplant recipients with high MELD scores.

Topics: Adult; Ampicillin; Anti-Bacterial Agents; Antibiotic Prophylaxis; End Stage Liver Disease; Female; Graft Survival; Humans; Incidence; Liver Transplantation; Male; Middle Aged; Pneumonia; Retrospective Studies; Sepsis; Severity of Illness Index; Sulbactam; Treatment Outcome

A new degradant of sultamicillin drug substance was found during the gradient reverse phase HPLC analysis of stability storage samples. The level of this degradant impurity was observed up to 1.0%. The impurity (formaldehyde adduct with 5-oxo-4-phenylimidazolidin-1-yl moiety) was identified by LC/MS and was characterized by ((1)H NMR, (13)C NMR, 2D-NMR ((1)H-(1)H COSY, NOESY, HSQC and HMBC), LC/MS/MS, MS/TOF, elemental analysis and IR. This impurity was prepared by isolation and co-injected into HPLC system to confirm the retention time.

Topics: Ampicillin; Chromatography, High Pressure Liquid; Chromatography, Liquid; Drug Contamination; Drug Stability; Humans; Magnetic Resonance Spectroscopy; Mass Spectrometry; Pneumonia; Spectrophotometry, Infrared; Sulbactam; Tandem Mass Spectrometry

A 5-year-old girl with no underlying immune deficiency or hematologic disease was treated with a combination of ceftriaxone and ampicilline-sulbactam for pneumonia. On the ninth day of the therapy, she developed oliguria, paleness, malaise, immune hemolytic anemia (IHA) and acute renal failure (ARF). Laboratory studies showed the presence of antibodies against ceftriaxone. Acute interstitial nephritis (AIN) was diagnosed by renal biopsy. The patient's renal insufficiency was successfully treated with peritoneal dialysis without any complications. The patient recovered without any treatment using steroids or other immunosuppressive agents.

Topics: Acute Disease; Acute Kidney Injury; Ampicillin; Anemia, Hemolytic; Anti-Bacterial Agents; Ceftriaxone; Child, Preschool; Coombs Test; Female; Humans; Immunoglobulin G; Nephritis, Interstitial; Peritoneal Dialysis; Pneumonia; Sulbactam; Treatment Outcome

Oral tablets containing 375 mg sultamicillin were used to treat 30 adult patients of either sex suffering from lower respiratory tract infections. The dose used was one tablet every 12 h for 22 cases and one tablet every 8 h for eight cases. The duration of therapy varied between 5 and 14 days (mean 8.6 days). The therapeutic response was rated as cure in 23 (76.6%) patients, with complete disappearance of pretreatment signs and symptoms, and as improvement in seven (23.3%) patients, with amelioration of the pretreatment manifestations. All 52 microorganisms isolated before treatment were eradicated. No adverse effects were reported in 25 (83.3%) patients, whereas the remaining five (16.7%) patients reported mild loose stools with normal bowel motion. There were no abnormal changes in blood count and liver and renal functions following sultamicillin treatment.

Topics: Acute Disease; Administration, Oral; Adult; Ampicillin; Bacterial Infections; Bronchitis; Chronic Disease; Drug Therapy, Combination; Female; Humans; Male; Pneumonia; Respiratory Tract Infections; Sulbactam; Tablets

Efficacy of sulbactam, a beta-lactamase inhibitor, in combination with ampicillin, was evaluated for treatment of experimentally induced pneumonia caused by beta-lactam-resistant Klebsiella pneumoniae. Infection was experimentally induced in 18 healthy weanling foals that were randomly allocated to 3 treatment groups: sulbactam plus ampicillin (S/A, 3.3 and 6.6 mg/kg of body weight, respectively), ampicillin (6.6 mg/kg), or vehicle only. Foals were treated daily for 7 days; the observer was unaware of treatment status. Compared with ampicillin and vehicle, treatment with S/A resulted in a statistically significant (P less than 0.05) decrease in severity of pneumonia, with regard to bronchoalveolar lavage cytologic findings (decreased total cell and neutrophil numbers, and increased lymphocyte numbers) and extent of macroscopic lesions in lung tissue of the noninoculated regions. Marked trends toward improvement of S/A-treated foals were observed for quantitative results of bacteriologic culture of bronchoalveolar lavage fluid samples (P less than 0.07), macroscopic pathologic features of the whole lung (P less than 0.1), and histopathologic variables (P less than 0.07), compared with ampicillin- and vehicle-treated foals. Treatment effects were not observed for radiographic, hematologic, and blood gas abnormalities that resulted from infection. In conclusion, the combination of sulbactam plus ampicillin was found to have synergistic effects in vivo, to reduce the extent and severity of experimentally induced gram-negative lung infection in foals.

Topics: Ampicillin; Animals; Bronchoalveolar Lavage Fluid; Drug Evaluation; Drug Synergism; Drug Therapy, Combination; Horse Diseases; Horses; Klebsiella Infections; Klebsiella pneumoniae; Lung; Pneumonia; Radiography; Random Allocation; Sulbactam

Haemophilus influenzae is a frequent cause of recurrent or chronic lower respiratory tract infections in patients suffering from cystic fibrosis (CF) and other chronic obstructive pulmonary disease (COPD). Ampicillin and its derivatives are routinely used in treatment, but resistant strains producing beta-lactamase frequently necessitate the use of other antibiotics. Sultamicillin is a compound agent for oral use in which ampicillin and the beta-lactamase inhibitor sulbactam are linked as a double ester. This combination is active in vitro against many beta-lactamase producing bacteria including ampicillin-resistant H. influenzae. Eight CF children and ten children with other COPD suffering from chronic or recurrent H. influenzae infection of the lower respiratory tract were treated with sultamicillin orally, 25 mg/kg, 12-hourly, for two weeks. Nine infections were caused by ampicillin-resistant strains. At the end of the treatment 65% of the patients were free of H. influenzae. The only adverse reaction was diarrhoea which occurred in 14 patients, and necessitated withdrawal of one patient from the study.

Topics: Adolescent; Ampicillin; Child; Child, Preschool; Cystic Fibrosis; Diarrhea; Drug Combinations; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Lung Diseases, Obstructive; Male; Penicillanic Acid; Pneumonia; Sulbactam