How to effectively administer drugs when encountering Pseudomonas aeruginosa?

*For medical professionals to read and refer to the summary of Pseudomonas aeruginosa medication, it is recommended to collect! Pseudomonas aeruginosa (PA) is a non-fermenting gram-negative bacillus, widely distributed in the environment, and domestic sewage is its main source; it can cause skin infections (more common in burn patients), lung infections, bloodstream infections,
etc.

At the same time, PA can also be found in healthcare settings, and PA often causes nosocomial infections (eg, pneumonia)
.

For patients with skin and mucous membrane damage (tracheal intubation, mechanical ventilation, indwelling central venous catheter, etc.
), low immunity, structural lung disease (chronic obstructive pulmonary disease, bronchiectasis, cystic fibrosis, etc.
), long-term hospitalization and Patients using broad-spectrum antibiotics have a higher risk of PA infection [1]
.

For patients with cystic fibrosis, respiratory tract infection caused by PA can even evolve into chronic infection, which makes clinical treatment more difficult
.

Figure 1 Aztreonam, aminoglycosides, polymyxins, and fosfomycin, the commonly used anti-PA drugs in China are generally not used alone for anti-PA, but are often used in combination with other antibacterial drugs
.

The anti-PA course of treatment is evaluated according to the clinical symptoms of the patient.
If the condition stabilizes within 3 days, the recommended anti-infective course of treatment is 8 days; if the anti-infective effect is not satisfactory, it can be extended to 10-14 days[1]
.

Therefore, the specific course of anti-PA should be adjusted according to the patient's condition, which can be appropriately extended or shortened
.

Research Prospects of Inhaled Antibiotics in the Treatment of PA-related Pulmonary Infections For pulmonary infections caused by PA, reducing the bacterial load of PA in the respiratory tract and eradicating PA can improve the prognosis of patients
.

Antibacterial drugs for inhalation have their unique dosage form advantages, which can accumulate in the respiratory tract and have a high local drug concentration, which can significantly improve the respiratory symptoms of patients and improve the quality of life of patients [2]
.

Tobramycin and polymyxin inhalation preparations are research hotspots.
With the continuous progress of medicine, the research field has been extended to aztreonam, amikacin and other drugs (Figure 2)
.

Soon, inhaled antimicrobials are expected to enter the domestic market and be used to treat infections caused by PA
.

Figure 2 The drug resistance mechanism and drug recommendation of PA PA can produce drug resistance by producing β-lactamase (such as carbapenemase), expressing efflux pumps, changing target sites and outer membrane proteins, and forming biofilms [3]
.

The 2020 China Bacterial Resistance Surveillance Network (CHINET) report pointed out that the resistance rate of PA to carbapenems is about 23%, but the resistance rate to polymyxin and amikacin is low [4]
.

Classification of drug-resistant PA: multi-drug resistance (MDR): insensitivity to 3 or more antibacterial drugs with anti-PA efficacy (including intermediary and drug resistance); pan-drug resistance (XDR): usually refers to PA that is only resistant to polyviscosity Sensitive to bacteriocin, but not to other drugs (Note: tigecycline is ineffective against PA); pan-resistant (PDR): PA is not sensitive to existing antibacterial drugs
.

Antibacterial drugs that can inhibit or destroy PA biofilm include: macrolides such as erythromycin, roxithromycin, clarithromycin, azithromycin, and quinolones such as ciprofloxacin and levofloxacin
.

The "two-combination" medication regimen of XDR-PA [5], see Figure 3: Figure 3 The "triple-combination" medication regimen of XDR-PA [3] Polymyxin + β-lactam + ciprofloxacin; Polymyxin + β-lactam + fosfomycin; polymyxin (intravenous) + polymyxin (aerosol inhalation) + carbapenems; aztreonam + ceftazidime + amikacin
.

The treatment of drug-resistant bacteria such as XDR-PA often requires combined use of antibacterial drugs, which increases the risk of adverse drug reactions (ADRs)
.

Such as aminoglycosides and polymyxins are nephrotoxic, patients should be monitored for renal function
.

Piperacillin and rifampicin can cause immune-mediated thrombocytopenia [6].
If piperacillin or rifampicin is used for the treatment of drug-resistant PA, the platelet count should be followed up
.

Therefore, rational selection of drugs and monitoring of patients' drug reactions are particularly important! Summary: Today, ceftazidime avibactam has gradually entered the clinic and is used for drug-resistant PA
.

But for XDR-PA, PDR-PA, etc.
, there is an urgent need for new antibacterial drugs to enter the clinic
.

Currently, ceftolozatazobactam, cefdil, finafloxacin, delafloxacin and other drugs are undergoing clinical trials [7-8], which are expected to be used for the treatment of severe infections caused by drug-resistant PA in the future
.

References: [1] Liu Youning, Shi Yi.
Expert consensus on the diagnosis and treatment of Pseudomonas aeruginosa lower respiratory tract infection [J].
Chinese Journal of Tuberculosis and Respiratory Medicine, 2014.
[2] Silva Filho LV, Ferreira Fde A, Reis FJ, Britto MC , Levy CE, Clark O, Ribeiro JD.
Pseudomonas aeruginosa infection in patients with cystic fibrosis:scientific evidence regarding clinical impact,diagnosis,and treatment.
J Bras Pneumol.
2013 Jun-Aug;39(4):495-512.
[3 ] Wang Minggui.
Laboratory diagnosis, antimicrobial treatment and nosocomial infection control of extensively drug-resistant gram-negative bacterial infection: Chinese expert consensus [J].
Chinese Journal of Infection and Chemotherapy, 2017, 17(1): 11.
[4] Hu Fupin, Guo Yan, Zhu Demei.
Surveillance of bacterial resistance in China by CHINET in 2020 [J].
Chinese Journal of Infection and Chemotherapy, 2021, 21(04): 377-387.
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2021.
04.
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[5]Ma W, Li J, Wang D, Yu C, Sun S.
In vitro interaction of various antibiotic combinations recommended by Chinese consensus statement against carbapenems-resistant Pseudomonas aeruginosa.
Lett Appl Microbiol.
2019 Sep;69(3):198-203.
[ 6] Mitta A, Curtis BR, Reese JA, George JN.
Drug-induced thrombocytopenia: 2019 Update of clinical and laboratory data.
Am J Hematol.
2019 Mar;94(3):E76-E78.
[7] Tamma PD, Aitken SL, Bonomo RA, et al.
Infectious Diseases Society of America Antimicrobial Resistant Treatment Guidance: Gram-Negative Bacterial Infections [J].
Clinical Infectious Diseases, 2020, 72(7).
[8] Ibrahim D , Jabbour JF, Kanj SS.
Current choices of antibiotic treatment for Pseudomonas aeruginosa infections.
Curr Opin Infect Dis.
2020 Dec;33(6):464-473.