sultamicillin and Critical-Illness

The purpose of this paper was to review the potential utility of ampicillin/sulbactam (SAM) as a therapy for serious infections in critically ill patients. Data for this review were identified by searches of PubMed and of the reference lists of the included articles. We found that SAM appears to have a number of characteristics that support its use in the treatment of serious infections in critically ill patients. SAM demonstrates extensive penetration into many infection sites, supporting its use in a wide range of infection types. Microbiologically, sulbactam has strong intrinsic antibiotic activity against multidrug-resistant (MDR) bacteria, including Acinetobacter baumannii, which supports its use for the treatment of infections mediated by this pathogen. Of some concern, there have been reports showing a decline in susceptibility of some bacteria to SAM. As such, use of lower doses (4/2g/day), particularly for MDR A. baumannii, has been linked with a 30% reduced success rate in critically ill patients. The therapeutic challenges for ensuring achievement of optimal dosing of SAM result partly from bacterial susceptibility but also from the pharmacokinetic (PK) alterations common to β-lactam agents in critical illness. These PK changes are likely to reduce the ability of standard dosing to achieve the concentrations observed in non-critically ill patients. Optimisation of therapy may be more likely with the use of higher doses, administration by 4h infusion or by combination therapy, particularly for the treatment of infections caused by MDR pathogens.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Ampicillin; Anti-Bacterial Agents; Critical Illness; Drug Resistance, Multiple, Bacterial; Humans; Sulbactam

This study was conducted to determine whether critically ill patients admitted to the intensive care unit (ICU) with sepsis and septic shock may benefit from extended infusion of ampicillin/sulbactam compared with those receiving intermittent infusion.. This randomized assessor-blinded clinical trial was conducted in the ICUs of Nemazee and Shahid Rajaee hospital, Shiraz, Iran, from August 2019 to August 2021. The participants randomly received 9 g Ampicillin/Sulbactam every 8 h by either extended (infused over 4 h) or intermittent (infused over 30 min) intravenous infusion if their estimated glomerular filtration rate based on Cockrorft-Gault formula was higher than 60 ml/min.. Totally, 136 patients were enrolled and allocated to the intervention and control groups, each with 68 patients. Clinical cure was significantly higher in the extended group (P = 0.039), but ICU and hospital length of stay did not differ between the groups (P = 0.87 and 0.83, respectively). The ICU (P = 0.031) and hospital (P = 0.037) mortality rates in the extended infusion group were significantly lower than those in the intermittent infusion group.. These data should be replicated in larger clinical trials before providing any recommendation in favor of this method of administration in clinical practice.

Topics: Ampicillin; Anti-Bacterial Agents; Critical Illness; Humans; Intensive Care Units; Prospective Studies; Sepsis; Shock, Septic; 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

Continuous infusion (CI) of beta-lactam-antibiotics may improve pharmacodynamics in critically ill patients, but resulting concentrations have not been studied. Therapeutic drug monitoring is increasingly used to ensure antibiotic concentration. The aim of this study is to evaluate therapeutic ampicillin/sulbactam concentrations of a continuous infusion regimen.. Medical records of all patients admitted to ICU between January 2019 and December 2020 were retrospectively reviewed. Each patient received a 2/1 g ampicillin/sulbactam loading dose, followed by a continuous infusion of 8/4 g per 24 h. Ampicillin serum concentrations were measured. Main outcomes were reaching of plasma concentrations breakpoint defined by minimum inhibitory concentration (MIC at 8 mg/l) and 4-fold MIC (MIC at 32 mg/l) during steady state of CI.. In 50 patients a total of 60 concentration measurements were performed. The first concentration was measured after a median of 29 h (IQR 21-61 h). Mean ampicillin concentration was 62.6 ± 39.1 mg/l. Furthermore, serum concentrations exceeded the defined MIC breakpoint in all measurements (100 %) and were above the 4-fold MIC in 43 analyses (71.1 %). However, patients suffering from acute kidney injury exhibited significant higher serum concentrations (81.1 ± 37.7 mg/l vs. 38.2 ± 24.8 mg/l; p < 0.001). Also, there was a negative correlation between ampicillin serum concentrations and GFR (r = -0.659; p < 0.001).. The described dosing regimen for ampicillin/sulbactam is safe with respect to the defined MIC breakpoints for ampicillin, and continuous subtherapeutic concentration is unlikely. However, with impaired renal function drug accumulation occurs, and with increased renal clearance, drug levels can be below the 4-fold MIC breakpoint.

Topics: Ampicillin; Anti-Bacterial Agents; Critical Illness; Humans; Microbial Sensitivity Tests; Retrospective Studies; Sulbactam

The fixed antibacterial combination of ampicillin and sulbactam is frequently used for various infections. Intact kidneys eliminate approximately 71% of ampicillin and 78% of sulbactam. Patients on thrice-weekly low-flux hemodialysis exhibit an ampicillin t(1/2) of 2.3 hours on and 17.4 hours off dialysis. Despite its frequent use in intensive care units, there are no available dosing recommendations for patients with AKI undergoing renal replacement therapy. The aims of this study were to evaluate the pharmacokinetics of ampicillin/sulbactam in critically ill patients with AKI undergoing extended dialysis (ED) and to establish a dosing recommendation for this treatment method.. Twelve critically ill patients with anuric AKI being treated with ED were enrolled in a prospective, open-label, observational pharmacokinetic study. Pharmacokinetics after a single dose of ampicillin/sulbactam (2 g/1 g) was obtained in 12 patients. Multiple-dose pharmacokinetics after 4 days of twice-daily ampicillin/sulbactam (2 g/1 g) was obtained in three patients.. The mean dialyzer clearance for ampicillin/sulbactam was 80.1 ± 7.7/83.3 ± 12.1 ml/min. The t(1/2) of ampicillin and sulbactam in patients with AKI undergoing ED were 2.8 ± 0.8 hours and 3.5 ± 1.5 hours, respectively. There was no significant accumulation using a twice-daily dosage of 2 g/1 g ampicillin/sulbactam.. Our data suggest that in patients treated with ED using a high-flux dialyzer (polysulphone, 1.3 m(2); blood and dialysate flow, 160 ml/min; treatment time, 480 minutes), a twice-daily dosing schedule of at least 2 g/1 g ampicillin/sulbactam, with one dose given after ED, should be used to avoid underdosing.

Topics: Acute Kidney Injury; Adult; Aged; Aged, 80 and over; Ampicillin; Anti-Bacterial Agents; Anuria; Area Under Curve; Critical Illness; Drug Administration Schedule; Drug Dosage Calculations; Drug Monitoring; Equipment Design; Female; Germany; Half-Life; Humans; Infusions, Intravenous; Male; Membranes, Artificial; Metabolic Clearance Rate; Middle Aged; Models, Biological; Polymers; Prospective Studies; Renal Dialysis; Sulbactam; Sulfones; Young Adult