Gram-negative bacterial infection in critically ill patients, optimal treatment plan of β-lactam antibiotics

*For reference only for medical professionals, the initial use of beta-lactam antibiotics requires a dosing strategy of prolonged infusion or continuous infusion to optimize the completion rate of anti-infective goals
.

 Aiming at the characteristics of antibiotic metabolism in intensive care unit (ICU) patients, Kelly L.
Maguigan and others recently published a review article "Beta-Lactams Dosing in Critically Ill Patients with Gram-Negative bacterial Infections: A PK/PD Approach" in the journal Antibiotics.
The optimal β-lactam antibiotic treatment regimen for Enterobacter and Pseudomonas aeruginosa was determined according to the drug susceptibility breakpoints established by the European Committee for Antimicrobial Susceptibility Testing (EUCAST)
.

This review comprehensively searches PubMed and Medline databases to assess the dosing issues of a variety of beta-lactam antimicrobials, including penicillins, cephalosporins, carbapenems, and monocyclic beta-lactams.
The details of the search are as follows : Penicillin class 1 Piperacillin/tazobactam In the United States, piperacillin/tazobactam is the only available penicillin class of antimicrobials with activity against Pseudomonas aeruginosa
.

Although the instructions recommend standard dose intermittent dosing, for critically ill patients, when the minimum inhibitory concentration (MIC) is 16 mg/L, the dosing strategy of 4.
5 g q6h is difficult to achieve a sufficiently effective antimicrobial drug exposure target
.

Prolonged infusion time of piperacillin/tazobactam has the potential to break the limitations of intermittent dosing strategies
.

Studies have confirmed that prolonging the infusion time can achieve 100% drug concentration time higher than MIC (100% fT>MIC), and achieve the improvement of 30-day survival rate, clinical cure rate and other prognostic indicators
.

However, in critically ill patients, prolonged infusion time still fails to achieve the recommended pharmacokinetic/pharmacodynamic (PK/PD) targets
.

Continuous infusion of piperacillin/tazobactam may be more advantageous for enhanced renal clearance in critically ill patients or infection with pathogens with higher MIC values
.

To verify this conclusion, the researchers retrieved the following studies: Robert et al evaluated the pharmacokinetics of 16 critically ill patients with normal renal function at the first dose and at steady state.
A group of patients received 16 g daily in intermittent, divided doses.
Piperacillin/tazobactam was administered, and another group of patients was given a loading initial dose of 4 g, followed by continuous infusion of 8 g and 12 g of piperacillin/tazobactam on the first and second days, respectively
.

Five blood samples were collected during the initial loading dose, 12 samples were collected after the loading dose, and 10 steady-state blood samples were collected the next day
.

At the same time, intermittent, prolonged infusion time, and continuous infusion dosing strategies were simulated in the population model
.

The results of the study showed that with MIC 0.
25mg/L as the standard, for 4g loading, according to the dosing strategy of q6h and q8h, the target achievement rate (PTA) (defined as the time when the free piperacillin concentration was greater than the MIC exceeded 50%) was administered.
drug intermittent) only 79% and 59%
.

However, with MICs of 4mg/L and 8mg/L as the standard, 12g and 16g continuous infusion strategies were able to achieve 100% PTA; when the MIC was 16mg/L, only the 16g continuous infusion strategy achieved 66% PTA
.

This suggests that higher drug doses are required for highly resistant pathogens
.

The next two studies retrieved included patients in the early stages of sepsis or septic shock who had renal impairment but did not require renal replacement therapy
.

Obrink-Hansen et al evaluated 15 patients with septic shock who were administered piperacillin 4g q8h within 3 minutes, and 8 blood samples were collected after the third dose to establish a pharmacokinetic model to evaluate the empirical dose
.

The researchers targeted the MIC of Pseudomonas aeruginosa (16 mg/L), and the PK/PD targets were 50% fT>4MIC and 100% fT>MIC
.

The results of the study showed that increased serum creatinine was closely associated with decreased clearance of piperacillin (P=0.
005), and patients with renal impairment were more likely to achieve the expected PK/PD goals
.

However, with a MIC of 16 mg/L as the target, even with a serum creatinine of 250 μmol/L, standard intermittent dosing (4 g q8h) could not achieve PTA>90%, and only a 16 g daily continuous infusion strategy could achieve this goal
.

With the MIC of 8mg/L as the standard, the continuous infusion strategy of 12g and 16g per day can achieve 100% fT>MIC and 50% fT>4MIC
.

Similar conclusions were found in Sukarnjanaset's study of 48 patients with severe sepsis complicated with renal impairment of different severity in the early stage
.

Low creatinine clearance (CrCL) and mean arterial pressure (MAP) are strongly associated with decreased piperacillin clearance
.

For pathogens with an MIC of 16 mg/L, patients with CrCL greater than 60 ml/min could not achieve 90% fT>MIC with the standard intermittent dosing strategy, while the dosing strategy of 4 g infusion time greater than 2 hours and q6h could achieve this goal
.

Dhaese and colleagues evaluated 110 surgical ICU patients not requiring renal replacement and extracorporeal membrane oxygenation support to determine the optimal dose of continuous infusion of piperacillin
.

Patients first received a 4g loading dose followed by a continuous infusion dosing strategy, with doses calculated according to CrCL: <15ml/min 8g/day; 15-29ml/min 12g/day; 30-129ml/min 16g/day; 130- 199ml/min 20g/day
.

  A target achievement rate (TA) >95% was defined as a successful dose with a target of 100% fT>4MIC
.

When MIC=8mg/L, 12g/day continuous infusion can achieve 100% TA for patients with CrCL>60ml/min
.

However, when the MIC 16mg/L was used as the standard, when the patient's CrCL exceeded 90ml/min, the continuous infusion of 24g per day could not achieve 100% TA, indicating that for patients with enhanced renal clearance, changes in antimicrobial therapy need to be considered scheme
.

Therefore, compared with intermittent dosing, continuous infusion of piperacillin/tazobactam can have a higher target achievement rate
.

Target levels of tazobactam are dependent on β-lactamase expression, and for strains expressing high levels of β-lactamase, target achievement (TA) was defined as free tazobactam concentrations greater than 85% of the dosing interval 2mg/L
.

A model based on 18 critically ill patients showed that the daily continuous infusion of 16/2g piperacillin/tazobactam can achieve a tazobactam target achievement rate of more than 75%
.

Also, the 16/2 g daily piperacillin/tazobactam continuous infusion regimen can produce adequate drug concentrations in the alveoli, while the 12/1.
5 g daily piperacillin/tazobactam continuous infusion dosing targets The achievement rate is slightly lower
.

Cephalosporin Class 1 Cefepime Early studies with cefepime suggest that continuous infusion or more frequent dosing may help achieve optimal TA in critically ill patients
.

Tam et al.
simulated different dosage regimens of cefepime through population PK model for different populations (healthy people, patients with renal insufficiency, patients with hepatic insufficiency, cystic fibrosis patients) and different CrCL (60, 90 and 120ml/min).
, PK/PD target selection is 83% fT>4.
3 times MIC
.

The results of the study showed that when the MIC target was 4mg/L (CrCL was 60ml/min), cefepime 2g q12h (6-hour infusion), 2g q8h (30-minute infusion) and 4g continuous infusion all achieved more than 80% target completion rate
.

Furthermore, 4 g cefepime continuous infusion can also achieve good goal completion rates when the MIC target is 4 mg/L (CrCL is any value) and the MIC target is 8 mg/L (CrCL is 60 ml/min)
.

When the MIC was significantly increased or the CrCL was significantly increased, the goal completion rate decreased significantly
.

Roos et al.
established a population pharmacokinetic model of cefepime using data from 13 ICU patients.
Each patient collected 12 blood samples after the first dose and at steady-state concentrations (3-6 days)
.

Targeting 65% fT > MIC, intermittent dosing of 2 g q8h and 1 g q4h achieved >80% TA at MIC of 4 mg/L, but decreased TA as MIC increased
.

In contrast, 2-6g, 4-6g, and 6g continuous infusion administration at 0.
5g loading could achieve good TA at MICs of 4mg/L, 8mg/L and 16mg/L, respectively
.

Another study established a pharmacokinetic model based on the concentration of cefepime in 26 patients with ventilator-associated pneumonia (VAP) in the ICU, which was confirmed in another 6 patients
.

The authors simulated cefepime 1-2g dosing every 8-12 hours and divided into 30-minute and 3-hour doses, using CrCL adjustments from 10-120ml/min, and 50% fT>MIC as the PK/PD target
.

The study found that when CrCL was lower than 50ml/min and MIC≤8mg/L, the target achievement rate was higher than 80% for all dosing regimens
.

When CrCL increased, the 2g q8h regimen could achieve the best TA at MICs of 4mg/L and 8mg/L, and the 3-hour continuous infusion was better than the 30-minute infusion regimen
.

Recently, a cefepime PK model including 266 ICU patients simulated different dosing regimens to assess the target achievement rate of 100% fT>MIC and 100% fT>4MIC
.

For the 100% fT>MIC target, when the MIC is 4 mg/L and 8 mg/L, respectively, the 2 g q6h or q8h dosing regimen requires extended infusion when the CrCL is less than 90ml/min
.

When CrCL is elevated (over 90ml/min) or the MIC is 16mg/L, a 4g loading dose is required, followed by a continuous infusion of 7-8g
.

For the 100% fT>4MIC target, only a 7-8g continuous infusion regimen was able to achieve 80% TA at a MIC of 4mg/L, but not at a MIC of 8mg/L
.

In two studies involving neurocritically ill patients, cefepime achieved MICs of 4 mg/L or 8 mg/L in both plasma and cerebrospinal fluid when administered as continuous infusion or q8h compared with q12h dosing regimens.
better TA
.

Also, patients on a continuous dosing regimen have shorter treatment cycles
.

The study also found that the continuous infusion of cefepime 4g has better penetration into the alveoli compared with intermittent infusion, and achieves better drug concentration in the alveolar epithelial lining
.

2 Ceftazidime Georges and colleagues established a ceftazidime population PK model based on the data of 49 ICU patients, and validated it with 23 patients
.

The study found that ceftazidime clearance was closely related to glomerular filtration rate (eGFR), central volume of distribution and peripheral volume of distribution at the site of infection
.

By simulating intermittent and continuous dosing regimens, the authors found that continuous infusion of 6g ceftazidime achieved better TA even with 100% fT>5×MIC as the PK/PD target, but patients with higher CrCL required higher drug levels dose
.

A retrospective study investigated the pharmacokinetics of a continuous infusion regimen of ceftazidime in 92 ICU patients with doses ranging from 1 g to 6 g per day, with a mean CrCL of 94 ml/L (range 14-258 ml/min)
.

The average concentration of ceftazidime in all patients was 46.
9ml/min.
Among the 51 patients diagnosed with infection, 84% achieved the target completion rate of 100% fT>5×MIC, and no reports of related adverse reactions were found
.

3 Ceftazidime/avibactam Stein et al evaluated the pharmacokinetics of ceftazidime/avibactam in 10 ICU patients
.

Plasma samples were collected 2, 4, 6, and 8 hours after the patients received multiple doses of antibiotics
.

When the MIC was as high as 16 mg/L, the target achievement rate of ceftazidime 50% fT>MIC and avibactam 50% fT>1 mg/L was more than 90% using a 2.
5g q8h continuous 2-hour infusion regimen
.

The program has shown a high target achievement rate in different indications such as PK models and clinical phase 3 data in different populations
.

For patients with severe intra-abdominal infection, continuous infusion of ceftazidime compared with intermittent dosing showed higher target achievement rates in both plasma and intraperitoneal fluid (100% fT>4MIC, 90% and 44%, respectively)
.

Likewise, the ceftazidime alveolar lining fluid concentration was higher with the continuous infusion regimen and the target achievement rate was higher
.

4 Ceftriaxone In the study on the pharmacokinetics of free ceftriaxone in patients, the 2g daily continuous infusion regimen of ceftriaxone can achieve the target completion rate of 100% fT>MIC when the MIC is 2mg/L, and the 2g q12h regimen Achieving 50% fT>MIC
.

In this PK model, CrCL was closely related to the clearance of free ceftriaxone, affecting the target achievement rate
.

The study found that enhanced renal clearance increases the likelihood that patients receiving ceftriaxone will fail to achieve the desired PK/PD target, and for patients with CrCL >200ml/min, a 2g q12h ceftriaxone dosing regimen may be required to achieve the desired outcome.
target completion rate
.

The PK model was established based on the plasma and cerebrospinal fluid samples of patients with bacterial meningitis.
Based on the patient's estimated eGFR and body weight, a twice-daily dosing regimen was established with a target ceftriaxone plasma concentration of 20-100 mg/L, and the daily dose was administered The amount ranges from 20-160mg/kg/d, and the eGFR ranges from 15-155ml/min/1.
73m2
.

The study found that patients receiving high-dose ceftriaxone had a median daily dose of 6.
5 g (range 4-9 g), a median drug concentration of 97.
5 mg/kg (range 77-131 mg/kg), and a median CSF concentration of 13.
3 mg /L (range 0.
9-91.
2mg/L)
.

5 Cefotaxime/tazobactam Sime et al.
established a population PK model based on the concentration of free cefotaxime/tazobactam in severe patients.
The study prospectively enrolled 12 patients and found that the clearance of the drug was related to urinary CrCL, and the The apparent volume of distribution (Vd) is related to body weight
.

In this study, by simulating different dosing regimens under different CrCL conditions, the target achievement rates of cefotaxime were 40%, 60% and 100% fT>MIC and tazobactam was 20% fT>1mg/L
.

It was found that when CrCL≤140ml/min/1.
73m2, 1.
5g q8h was enough to achieve a better target achievement rate
.

However, when the MIC is elevated or the patient's renal clearance is enhanced, a 1.
5 g loading dose is required, followed by a 4.
5 g continuous infusion
.

Another prospective study evaluated cefotaxime/tazobactam at different PK/PD targets and MICs by intermittent dosing, prolonged dosing, and continuous dosing regimens
.

When the MIC is as high as 16 mg/L, for the PK/PD target of 100% fT>MIC, 2g q8h infusion for 4 hours or continuous infusion can achieve better TA
.

However, for a 100% fT>4MIC target, only 6g continuous infusion administration at an MIC of 8mg/L was able to achieve >90% target achievement
.

CSF penetration of cefotaxime/tazobactam has also been evaluated in some studies
.

This study found that both 3g q8h and 9g continuous infusion regimens had lower CSF target achievement rates, and the alveolar penetration rate of patients receiving 3g q8h was even only about 50%, and due to different renal function.
and changed
.

During the dosing interval, the mean concentrations of cefotaxime/tazobactam were above 4 mg/L and 1 mg/L, respectively
.

Carbapenems 1 Meropenem Previous studies have found that compared with non-severely ill patients, the use of meropenem in ICU patients, especially for strains with an MIC of 4 mg/L or 8 mg/L, usually requires prolonged infusion time to reduce mortality in critically ill patients , Improve the clinical cure rate
.

Early PK models confirmed that in patients with normal renal function, meropenem usually requires prolonged infusion time or even continuous infusion to achieve cumulative fractional effect (CFR) and higher plasma concentrations
.

Roberts et al.
collected 10 patients with severe sepsis with normal renal function, and collected 15 steady-state concentrations on the first day and 9 on the 2-5th day to establish a pharmacokinetic model
.

Target achievement (PTA) was defined as 40% fT > MIC and a CFR of 100% of the dose was considered successful
.

The researchers found that the clearance of meropenem is dependent on renal function, and it is difficult for strains with high MIC values ​​to achieve the PK/PD target.
100% and 96.
9% CFR, respectively, can be achieved with the 2 g q8h regimen as an extended infusion every 4 hours
.

Minichmayr et al.
collected steady-state blood samples from 195 critically ill patients, and established a dose nomogram for continuous infusion of meropenem in critically ill patients with different degrees of renal impairment
.

Patients received meropenem at 0.
5-6 g/L, and all collected concentrations exceeded 2 mg/L
.

In addition, 99.
8% and 90.
3% of patients had plasma concentrations exceeding 4 mg/L and 8 mg/L, respectively
.

A nomogram was developed to estimate the required daily dose using the Cockcroft-Gault formula and the desired target concentration.
To achieve a target concentration of 16 mg/L, the daily dose was estimated using the following formula: 0.
0378×CrCL+1.
07
.

To achieve alveolar epithelial lining fluid concentration of 50% fT > MIC, the total daily amount of meropenem needs to be increased
.

Benitez-Cano et al.
monitored the alveolar epithelial lining fluid concentration of continuous infusion of meropenem.
They found that a loading dose of 2 g followed by continuous infusion of 3 g per day could achieve ideal PTA for pathogens with an MIC of less than 2 mg/L
.

However, for pathogens with a MIC as high as 2 mg/L, continuous infusion of 6 g/d meropenem is required to achieve a PTA of more than 90%
.

Therefore, continuous infusion of higher doses of meropenem is necessary for patients with severe lung infections
.

2 Imipenem Imipenem is usually used in combination with the renal dehydrogenase inhibitor cilastatin for anti-infective therapy
.

The IMPACT study used imipenem infusion within 30 minutes, q8h, and evaluated 51 ICU patients with VAP in 6 steady-state concentration samples before and after the fourth dose, and established a population model to evaluate the dosing strategy
.

PTA is defined as 40% of the time the drug concentration is higher than the MIC (40% fT>MIC)
.

The study found that at an MIC of 2 mg/L, 99.
1% of the simulated patients using the 0.
75g q6h dosing regimen and 99.
4% of the simulated patients using the 1g q6h dosing regimen achieved PTA
.

At the MIC of 4 mg/L, PTA was significantly reduced, 33% and 45%, respectively, but higher than the q8h interval dosing regimen of the same drug dose (14% and 21%, respectively)
.

Chen et al.
obtained similar results by analyzing 580 plasma samples of 247 ICU patients to detect the concentration level of imipenem, and established a population pharmacokinetic model
.

When the MICs were 2 mg/L and 4 mg/L, respectively, the 0.
75 g q6h dosing regimen could achieve the therapeutic target of 40% fT>MIC in 99.
5% and 96.
5% of the simulated population, and 70% in 90.
8% and 67.
8% of the patients.
fT>MIC
.

The authors suggest that a 1g q6h regimen can be used for highly resistant pathogens
.

In addition, Jaruratanasirikul et al.
studied the target achievement rate of imipenem in 50 ICU patients with different eGFR: for patients with eGFR of 60-120ml/min, when the target is 75% fT>MIC, it takes 4 hours of continuous infusion Dosing by injection to achieve 90% PTA, 0.
5g q6h administration when the MIC is 2mg/L, and 1g q6h regimen dosing when the MIC is 4mg/L
.

For patients with an eGFR of 30-59ml/min, at MIC of 2mg/L, at least 90% PTA can be achieved by infusion of 0.
5g q8h within 4 hours or 0.
5g q6h by infusion within 1 hour; At 4 mg/L, a 1-hour infusion of 1g q6h or a 1-hour infusion of 1g q8h is required
.

For patients with an eGFR of 15-29.
9 ml/min, a 0.
5 g q8h regimen (1 hour or 4 hour continuous infusion) is required at an MIC of 2 mg/L, and 0.
5 at an MIC of 4 mg/L Dosing on a g q6h schedule (1 hour or 4 hour continuous infusion)
.

3 Doripenem Robert et al conducted the first study to evaluate doripenem PK/PD parameters.
They studied 31 patients with severe hospital-acquired pneumonia who received 250 mg or 500 mg of doripenem, respectively, with 30min, 1 hour or A 4-hour infusion regimen, with 5-6 samples collected at steady state and between dosing intervals, was assessed with a target of 40% fT>MIC and 90% fT>MIC
.

The study found that for pathogens with MIC less than 2mg/L, when the patient's CrCL was 100ml/min, the 1-hour or 4-hour infusion of the 500mg q8h regimen could achieve the expected PK/PD target
.

For patients with enhanced renal clearance (CrCL 150 ml/min), the infusion time should be extended to 4 hours for administration
.

Jaruratanasirikul and colleagues found that achieving 40% fT>MIC and 80% fT>MIC required a larger dose of the drug, and the 1 g q8h regimen was administered for 1 hour and 4 hours, and the target achievement rate of 40% fT>MIC was 93%.
And 98%, 2g q8h regimen 4 hours continuous infusion is the only regimen that can achieve 80% fT>MIC and achieve more than 90% PTA
.

Of course, higher alveolar epithelial lining fluid concentrations can also be achieved with a 4-hour infusion than with a 1-hour infusion
.

4 Ertapenem Ertapenem has no anti-Pseudomonas aeruginosa activity, but can be used to treat Enterobacterial infections
.

Sufficient concentrations above MIC90 were detected in both plasma and alveolar epithelial lining fluid in VAP patients receiving the standard dose of 1 g per day
.

However, PK models in ICU patients are rarely studied
.

Burkhardt et al.
collected free drug concentrations in 17 patients with severe VAP who received 1g q24h ertapenem treatment to establish a PK model
.

Compared with healthy controls, these enrolled patients had increased Vd, increased clearance, and thus decreased peak drug concentrations and decreased area under the concentration-time curve
.

In this model, plasma concentrations were 2 mg/L at 6-hour dosing intervals, which may be related to lower serum albumin levels in this population
.

Therefore, the researchers suggest that for critically ill patients with hypoalbuminemia, the dosing interval should be shortened or changed to continuous infusion dosing
.

However, data on the stability of continuous infusion of ertapenem are lacking
.

Liebchen et al.
reached a controversial conclusion in 6 patients with hypoalbuminemia.
Under the standard dosing regimen of ertapenem, the drug concentration of 100% of the dosing interval exceeded 0.
25 mg/L, and 72% of the dosing interval had a drug concentration of more than 0.
25 mg/L.
The drug concentration is more than 2mg/L, and these results need further study to confirm
.

The monoamide ring aztreonam is a monoamide ring antibacterial drug that is often used for the empirical treatment of aerobic Gram-negative bacterial infections in patients with a history of immunoglobulin E-mediated allergy
.

In addition, aztreonam plays an increasingly important role in the treatment of resistant Gram-negative bacteria, such as metallo-beta-lactamase-producing Enterobacteriaceae
.

For ICU patients with normal renal function, the recommended dose of aztreonam is 2g q6-8h, but the dose should be halved when CrCL is 10-30ml/min/1.
73m2, and the dose should be given when CrCL is less than 10ml/min/1.
73m2 The dose should be reduced to 1/4
.

Cornwell et al.
evaluated the pharmacokinetics of aztreonam in 30 critical surgical ICU patients.
The dosing regimen was 2 g q6h, administered by infusion over 30 minutes.
The trough concentration and the blood drug at 30min, 2.
5h and 5h after administration were collected respectively.
concentration
.

The target drug concentration was ≥8 mg/L, but the MIC value of the isolated pathogen was not reported
.

The included patients were mainly young male adult patients with pulmonary infection or intra-abdominal infection.
Although the observed Vd of patients was 0.
35L/kg, which was significantly higher than that of healthy volunteers of 0.
18L/kg, the study found that 68% of the patients were administered during the entire administration.
Interval plasma concentrations were ≥8 mg/L, and 89% of patients had aztreonam concentrations exceeding 8 mg/L
.

For 9 patients whose trough concentration did not reach 8 mg/L, 8 were clinically cured
.

Therefore, despite the increase in Vd, the aztreonam 2g q6h 30min infusion regimen can achieve satisfactory TA for the young critically operative patient population
.

McKindley et al also evaluated the pharmacokinetics of aztreonam in adult trauma patients receiving mechanical ventilation who were treated for pneumonia
.

These patients received an infusion regimen of aztreonam 2 g q6h over 30 minutes, and blood samples were collected at 0.
5h, 1h, 2h, 4h, and 7h after dosing
.

To assess the distribution of aztreonam in the lungs, sputum samples were collected 2 hours after the end of the infusion
.

Nine patients with normal renal function and a mean age of 51 years were included in the study
.

Compared with the normal control population, the study found that the patients' aztreonam Vd increased significantly on days 2-3 and 7-8 (0.
42 and 0.
31 vs 0.
21L/kg, P<0.
05), and the half-life was prolonged (3.
9h vs 1.
7 h, P<0.
05), there was no significant difference in clearance, and the estimated CrCL was significantly correlated with the clearance of aztreonam on days 2-3
.

The mean drug concentration of aztreonam in sputum on days 2-3 was 5.
9 mg/L, and the concentration of aztreonam in 1 patient on days 7-8 was 9.
7 mg/L, but due to the lack of specimen volume, the results were not comparable sex
.

Similar to the findings of Cornwell et al.
, which demonstrated increased Vd in critically ill patients, a 2 g q8h dosing regimen was adequate in severely traumatized patients
.

Falcone and colleagues established a PK model in adult patients infected with carbapenemase-producing Enterobacter and receiving aztreonam in combination with ceftazidime/avibactam
.

Forty-one patients were included in the model, and 20 patients were admitted to the ICU during the analysis period
.

The mean age of the patients was 75 years, the median BMI was 23.
9kg/m2, and the antibiotic regimen was 1-2g q8h, 2-hour infusion
.

Blood samples were collected before the 1st, 4th, and 5th doses, after the end of the infusion, and at the midpoint of the infusion interval.

.

The study found that: when the MIC is 4mg/L, when the eGFR is 15-120ml/min, the lowest simulated dose to achieve 90% PTA is 1g q8h, and when the eGFR exceeds 120ml/min, 2g q8h is required
.

At MIC of 8mg/L, reaching 90% PTA, the dose of aztreonam is 1g q8h at eGFR 15-60ml/min, 2g q8h at eGFR 60-90ml/min, 2g q6h at eGFR 90-120ml/min, Or 2g loading dose followed by 8g daily continuous infusion
.

When the MIC is 16mg/L, 90% PTA can only be achieved when the eGFR is less than 90ml/min.
When the eGFR is 15-30ml/min, the aztreonam 1g q8h regimen is required, and the eGFR 30-60ml/min requires the aztreonam 2g q6h regimen.
, eGFR 60-90ml/min requires a 2g loading dose of aztreonam, followed by a daily continuous infusion of 8g
.

Table 1 shows the recommended initial dose of β-lactam antibiotics in the event of resistant Gram-negative infections
.

The recommended regimen is for patients with normal organ function, and when clinically feasible, the use of therapeutic drug monitoring to optimize the dosing regimen is recommended
.

Table 1 Recommendations for the initial dosage of β-lactam antibiotics in patients with normal liver and kidney function due to resistant Gram-negative bacteria When critically ill patients are shown to be less susceptible to infection with Gram-negative bacteria, initiation of β-lactam antibiotics requires a dosing strategy of prolonged infusion or continuous infusion to optimize the completion rate of anti-infective goals, especially for renal This is especially true in patients with enhanced clearance
.

Patients with impaired renal function also typically require prolonged infusion time regimens to achieve PK/PD goals, and it is recommended that therapeutic drug monitoring should be used to achieve individualized therapy
.

e2019209.
24.
Kuhn,D.
; Metz, C.
; Seiler, F.
; et al.
Antibiotic therapeutic drug monitoring inintensive care patients treated with different modalities of extracorporealmembrane oxygenation (ECMO) and renal replacement therapy: A prospective,observational single- center study.
Crit.
Care 2020, 24, 1–11.
This article is only used to provide scientific information to medical and health professionals, and does not represent the platform’s position Continuous infusion of lactam antibiotics can achieve satisfactory PK/PD goals 2.
The latest research shows that the risk of death from non-CP-CRE infection is 2.
4 times higher than that of CP-CRE! 3.
In-depth analysis of the 2021 SSC guidelines, focusing on anti-infective treatment of sepsis 4.
Carbapenem-resistant Enterobacteriaceae infections make treatment more difficult.
What are the advantages of combined therapy? 5.
The demand for the combined application of antibiotics is becoming more and more urgent.
Do you know all of these four in vitro combined drug susceptibility tests? 6.
Meropenem and therapeutic drug monitoring, these issues are worth knowing! 7.
The use of antibiotics in severe infections and the monitoring of therapeutic drugs are worthy of attention! 8.
What is the in vitro efficacy of antibiotic combination therapy on carbapenem-resistant Gram-negative bacteria? See what this review has to say? 9.
The in vitro antibacterial activity monitoring report of meropenem is here! Let's take a look at the latest monitoring data together 10.
PK/PD target system helps optimize clinical antibiotic drug regimen Copyright notice: This information is intended to help medical and health professionals better understand the latest developments in related disease areas Antibiotic therapeutic drug monitoring inintensive care patients treated with different modalities of extracorporealmembrane oxygenation (ECMO) and renal replacement therapy: A prospective,observational single-center study.
Crit.
Care 2020, 24, 1–11.
Scientific information provided by professionals does not represent the platform's position.
Review of previous highlights: 1.
In severe patients with Gram-negative bacterial infection, continuous infusion of β-lactam antibiotics can achieve satisfactory PK/PD goals 2.
Latest research, non -CP-CRE infection death risk is 2.
4 times higher than CP-CRE! 3.
In-depth analysis of the 2021 SSC guidelines, focusing on anti-infective treatment of sepsis 4.
Carbapenem-resistant Enterobacteriaceae infections make treatment more difficult.
What are the advantages of combined therapy? 5.
The demand for the combined application of antibiotics is becoming more and more urgent.
Do you know all of these four in vitro combined drug susceptibility tests? 6.
Meropenem and therapeutic drug monitoring, these issues are worth knowing! 7.
The use of antibiotics in severe infections and the monitoring of therapeutic drugs are worthy of attention! 8.
What is the in vitro efficacy of antibiotic combination therapy on carbapenem-resistant Gram-negative bacteria? See what this review has to say? 9.
The in vitro antibacterial activity monitoring report of meropenem is here! Let's take a look at the latest monitoring data together 10.
PK/PD target system helps optimize clinical antibiotic drug regimen Copyright notice: This information is intended to help medical and health professionals better understand the latest developments in related disease areas Antibiotic therapeutic drug monitoring inintensive care patients treated with different modalities of extracorporealmembrane oxygenation (ECMO) and renal replacement therapy: A prospective,observational single-center study.
Crit.
Care 2020, 24, 1–11.
Scientific information provided by professionals does not represent the platform's position.
Review of previous highlights: 1.
In severe patients with Gram-negative bacterial infection, continuous infusion of β-lactam antibiotics can achieve satisfactory PK/PD goals 2.
Latest research, non -CP-CRE infection death risk is 2.
4 times higher than CP-CRE! 3.
In-depth analysis of the 2021 SSC guidelines, focusing on anti-infective treatment of sepsis 4.
Carbapenem-resistant Enterobacteriaceae infections make treatment more difficult.
What are the advantages of combined therapy? 5.
The demand for the combined application of antibiotics is becoming more and more urgent.
Do you know all of these four in vitro combined drug susceptibility tests? 6.
Meropenem and therapeutic drug monitoring, these issues are worth knowing! 7.
The use of antibiotics in severe infections and the monitoring of therapeutic drugs are worthy of attention! 8.
What is the in vitro efficacy of antibiotic combination therapy on carbapenem-resistant Gram-negative bacteria? See what this review has to say? 9.
The in vitro antibacterial activity monitoring report of meropenem is here! Let's take a look at the latest monitoring data together 10.
PK/PD target system helps optimize clinical antibiotic drug regimen Copyright notice: This information is intended to help medical and health professionals better understand the latest developments in related disease areas This article is only used to provide scientific information to medical and health professionals, and does not represent the platform's position.
Review of past highlights: 1.
In severe patients with Gram-negative bacterial infection, continuous infusion of β-lactam antibiotics can achieve satisfactory PK/ PD goal 2.
The latest research shows that the risk of death from non-CP-CRE infection is 2.
4 times higher than that of CP-CRE! 3.
In-depth analysis of the 2021 SSC guidelines, focusing on anti-infective treatment of sepsis 4.
Carbapenem-resistant Enterobacteriaceae infections make treatment more difficult.
What are the advantages of combined therapy? 5.
The demand for the combined application of antibiotics is becoming more and more urgent.
Do you know all of these four in vitro combined drug susceptibility tests? 6.
Meropenem and therapeutic drug monitoring, these issues are worth knowing! 7.
The use of antibiotics in severe infections and the monitoring of therapeutic drugs are worthy of attention! 8.
What is the in vitro efficacy of antibiotic combination therapy on carbapenem-resistant Gram-negative bacteria? See what this review has to say? 9.
The in vitro antibacterial activity monitoring report of meropenem is here! Let's take a look at the latest monitoring data together 10.
PK/PD target system helps optimize clinical antibiotic drug regimen Copyright notice: This information is intended to help medical and health professionals better understand the latest developments in related disease areas This article is only used to provide scientific information to medical and health professionals, and does not represent the platform's position.
Review of past highlights: 1.
In severe patients with Gram-negative bacterial infection, continuous infusion of β-lactam antibiotics can achieve satisfactory PK/ PD goal 2.
The latest research shows that the risk of death from non-CP-CRE infection is 2.
4 times higher than that of CP-CRE! 3.
In-depth analysis of the 2021 SSC guidelines, focusing on anti-infective treatment of sepsis 4.
Carbapenem-resistant Enterobacteriaceae infections make treatment more difficult.
What are the advantages of combined therapy? 5.
The demand for the combined application of antibiotics is becoming more and more urgent.
Do you know all of these four in vitro combined drug susceptibility tests? 6.
Meropenem and therapeutic drug monitoring, these issues are worth knowing! 7.
The use of antibiotics in severe infections and the monitoring of therapeutic drugs are worthy of attention! 8.
What is the in vitro efficacy of antibiotic combination therapy on carbapenem-resistant Gram-negative bacteria? See what this review has to say? 9.
The in vitro antibacterial activity monitoring report of meropenem is here! Let's take a look at the latest monitoring data together 10.
PK/PD target system helps optimize clinical antibiotic drug regimen Copyright notice: This information is intended to help medical and health professionals better understand the latest developments in related disease areas
.

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