Imipenem + vancomycin ineffective pneumonia, and finally only use it to get it done

Case review

A 55-year-old man who was previously in good health was admitted to hospital for 3 days with fever and cough.

The patient had fever 3 days earlier, peaking at 40 °C, with dry cough, chest tightness, fatigue and unresponsiveness, and urinary incontinence.

Physical examination: body temperature 36.0 °C, blood pressure 105/56 mmHg, R 35 times/ min, finger oxygen 92% (in the mask noninvasive ventilation, oxygen concentration 60%), drowsiness, exhalation, two lungs wet sound, heart rate 90 beats / min, rhythm, no murmur, no edema of the lower extremities.

Laboratory tests:

Complete blood count: WBC 4.05 × 109/L, N% 85.4%, lymphocyte count 0.38 ×109/L, CRP > 220 mg/L, PCT 14.99 ng/mL;

血生化：AST 283 U/L，ALT 91 U/L，LDH > 2150 U/L，BUN 15 mmol/L ，Cr 295 μmol/L，Na+132.7 mmol/L；

Blood gas analysis: PH 7.37, PaO266 mmHg (FiO2 60%), PaCO256 mmHg;

COVID-19 nucleic acid detection (-), influenza detection (-);

CT chest: showing inflammation of the upper and middle lobes of the left lung and the middle lobes of the right lung.

Diagnosis: severe community-acquired pneumonia, respiratory failure.

After continued deterioration of oxygenation, the emergency endotracheal intubation was admitted to the respiratory department after mechanical ventilation.

At that time, the doctor on duty analyzed that the severe community-acquired pneumonia (SCAP) was critically ill and had a high mortality rate, and the combination of carbapenems combined with vancomycin/ linezolid, the "ace + ace" combination of heavy punches, broad-spectrum coverage of drug-resistant gram-negative bacteria and drug-resistant gram-positive bacteria (including MRSA), the large encirclement was reasonable, so the empiric antibacterial therapy of imipenem / cilastatin + vancomycin was chosen.

Q: Is the above plan reasonable?

A: Unreasonable, the reasons are as follows:

Guide recommended

2016 Chinese Adult CAP Diagnosis and Treatment Guidelines[1]:

Penicillin/enzyme inhibitor complex, tertiary cephalosporins, ertapenem plus macrolides, or respiratory quinolones alone are recommended for patients with severe CAP in young adults without underlying disease who require admission to the ICU, while combination (II B) is recommended for elderly patients with underlying disease.

The China Guide further layers SCAP:

# Young adults without underlying disease may choose to include an β-lactam combined macrolide regimen of ertapenem, or respiratory quinolones alone;

# Carbapenems such as ertapenem combined with macrolides or respiratory quinolones are recommended in the elderly (table 1). (Note: Ertapenem is a relatively alternative carbapenem, the antibacterial spectrum is narrow, the antibacterial effect on pseudomonas aeruginosa, Acinetobacter and other non-fermented bacteria is poor, but the half-life is longer, can be qd, more convenient.) ）

Table 1 Initial empiric anti-infective drug selection for SCAP

This patient is a young adult without underlying disease, and guidelines do not recommend imipenem /cilastatin, nor do they recommend anti-MRSA drugs such as vancomycin or linezolid.

IDSA/ATS Guidelines for the Diagnosis and Treatment of Community-Acquired Pneumonia (2019)[2]:

SCAP scheme: β-lactams + macrolides or β-lactams + respiratory quinolones (table 2)

Table 2 Standard treatment options for community-acquired pneumonia

The U.S. guidelines only recommend β-lactams in general (including penicillins, cephalosporins, and carbapenems), nor do they recommend routine coverage of MRSA with vancomycin or linezolid.

The shortcomings of the "Ace Combo Solution"

One. Overtreatment

Carbapenem antibacterial drugs have a wide antibacterial spectrum and strong antibacterial activity, and have antibacterial effects on aerobic and anaerobic bacteria, especially for multidrug-resistant gram-negative bacilli, such as ultra-broad-spectrum β-lactamase (ESBL) Enterobacteriaceae bacteria have strong antibacterial activity.

Patients aged ≥ 65 years of age or hospitalized CAP with underlying medical conditions (e.g., congestive heart failure, cardiovascular and cerebrovascular disease, chronic respiratory disease, renal failure, diabetes, etc.) should be considered for the possibility of enterobacteriaceae bacterial infection, and the risk of ESBL infection (presence of colonization or infection of ESBL bacteria, use of three generations of cephalosporins, repeated or prolonged hospitalization, indwelling implants, renal replacement therapy, etc.), empiric therapy with cephalomycin, piperacillin/or Tazobactam or cefoperazone/sulbactam, ertapenem, etc. (III B)[1].

In 2018, the National Health Commission issued the "Expert Consensus on the Clinical Application of Carbapenem Antibacterial Drugs"[3], which requires severe patients with multi-drug-resistant bacteria infection to have indications for the use of carbapenem antibacterial drugs, while this patient is a young adult without underlying diseases, and the risk of drug-resistant bacteria infection is not high.

Bacterial drug resistance has become a major challenge in the field of global public health and a worldwide problem of widespread concern to societies in all countries. The irrational use of antibiotics such as carbapenems in the clinic can lead to an increase in bacterial drug resistance, so it is necessary to strictly grasp the clinical application indications of antibacterial drugs, especially special grade antibacterial drugs such as carbapenems, in order to delay the rising trend of drug-resistant bacteria.

At present, the more difficult drug-resistant bacteria are carbapene-resistant Klebsiella pneumoniae (CRKP), CRKP infection is difficult to treat, mortality is high, and many studies have found that prior carbapene exposure is one of the important risk factors for CRKP infection [4].

Continental community-acquired drug-resistant Stabelliferella carpacifolide (CA-MRSA) is uncommon and over-medicated [5]. Community Staphylococcus aureus pneumonia is uncommon and is generally seen after influenza viral pneumonia, and such patients may be considered to have MRSA coverage.

Two. Atypical pathogens are not covered

SCAP's important pathogens are legionella, chlamydia, the treatment of drugs are macrolides (azithromycin, etc.), tetracyclines (doxycycline, minocycline) and quinolones (levofloxacin, moxifloxacin), and the ace combination of carbapenemenes + vancomycin / linezolid seems to be very powerful, but it is ineffective. Therefore, this ace combination scheme is too much to go, there is both overtreatment and insufficient treatment, and should not be used routinely. (Mainland azithromycin has a higher rate of resistance to Mycoplasma pneumoniae, so why does SCAP recommend a combination of azithromycin?) The main reason is that Mycoplasma pneumoniae pneumonia is a self-limiting disease, and severe pneumonia is rare)

Follow-up

This patient was initially admitted to the hospital with empiric imipenem / cilastatin + vancomycin antibacterial therapy, but still continued to have high fever, oxygenation did not improve, on the 5th day alveolar lavage fluid reported Legionella pneumophila detection, pathogenic diagnosis: Legionella pneumonia, so switched to azithromycin antibacterial therapy, the patient's condition improved, the body temperature gradually normalized, and finally offline extubation, smooth discharge.

summary

1. Severe pneumonia is not the same as drug-resistant bacterial infection, and it is not necessary to routinely use antibiotics against resistant bacteria such as carbapenems, vancomycin/linezolid;

2. SCAP preferred β-lactams combined with azithromycin/respiratory quinolones, and carbapenes may be considered in the elderly or those at risk of drug-resistant bacteria with underlying disease;

3. CA-MRSA is rare and should not be routinely used with vancomycin or linezolid;

4. Standardize diagnosis and treatment and rational use of antimicrobial drugs to reduce the mortality rate of SCAP and slow down the rise of bacterial drug resistance.

bibliography

1. Respiratory Diseases Branch of Chinese Medical Association; Guidelines for the Diagnosis and Treatment of Adult Community-Acquired Pneumonia in China (2016 Edition). Chinese Journal of Tuberculosis and Respiratory Diseases 2016; 39:253-279 AB. doi: 10.3760/cma.j.issn.1001-0939.2016.04.005.

2. Metlay JP, Waterer GW, Long AC, Anzueto A, Brozek J, Crothers K, et al. Diagnosis and Treatment of Adults with Community-acquired Pneumonia. An Official Clinical Practice Guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med 2019;200:e45–67. doi: 10.1164/rccm.201908-1581ST.

3. National Health Commission of the People's Republic of China. Expert consensus on the clinical application of carbapenem antimicrobials. http://www.nhc.gov.cn/yzygj/s7659/201809/95f65ca473b44746b24590e94468b8ff.shtml

4. Hsu J-Y, Chuang Y-C, Wang J-T, Chen Y-C, Hsieh S-M. Healthcare-associated carbapenem-resistant Klebsiella pneumoniae bloodstream infections: Risk factors, mortality, and antimicrobial susceptibility, 2017-2019. J Formos Med Assoc 2021;120:1994–2002. doi: 10.1016/j.jfma.2021.04.014.

5. Liu Jian, Zhang Jing, Cheng Qijian, et al. A questionnaire survey of physicians in Shanghai on the current status of diagnosis and treatment of community-acquired pneumonia[J] . Chinese Journal of Tuberculosis and Respiratory Diseases,2018,41(4): 288-295. DOI: 10.3760/cma.j.issn.1001-0939.2018.04.008. 2018.

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