Methicillin-resistant staphylococcus aureus (MRSA) is an important cause of hospital-acquired and community-associated infections [1], and since MRSA was first identified in 1961 [2], its isolation rate has been increasing, and according to the 2009 China CHINET Bacterial Drug resistance surveillance reported that the proportion of MRSA among 4114 strains of Staphylococcus aureus (hereafter referred to as S. aureus) clinically isolated from 14 teaching hospitals in 10 provinces and cities in China was as high as 52.7% [3] (the situation was similar in 2010, with 51.7% of MRSA among 4452 strains of S. aureus).MRSA is known to be the most important gram-positive cocci for hospital-acquired infections, and foreign countries have The situation is extremely serious as MRSA pneumonia is one of the most common types of clinical infections. MRSA pneumonia is one of the most common types of clinical infections, and its diagnosis and treatment are extremely challenging and need to be taken seriously.
Definition
The main respiratory MRSA infections are Community-Associated MRSA Pneumonia (CAMP) and Hospital Associated MRSA Pneumonia (HAP), the latter including Ventilator-Associated Pneumonia (VAP). Associated Pneumonia (VAP), and Healthcare Associated Pneumonia (HCAP).
Community-associated MRSA pneumonia (CA-MRSA pneumonia): also known as Community-Acquired MRSA Pneumonia, is defined as pneumonia in which the MRSA strain is isolated within 48 h of outpatient or hospital admission and there is no history of hospitalization or contact with a healthcare facility within 1 year, no history of MRSA infection or colonization, no indwelling catheters and other percutaneous medical device use history [4,5].
Hospital-associated MRSA pneumonia (HA-MRSA pneumonia): also known as Hospital-Acquired MRSA Pneumonia (HAP), is an inflammation of the lung parenchyma caused by MRSA that is not present at the time of patient admission but occurs 48 h after admission, and is the main manifestation of MRSA pneumonia. vap is a special form of HAP that It is pneumonia that occurs 48-72h after tracheal intubation. Health care facility-associated pneumonia (HCA-MRSA pneumonia) is pneumonia that occurs in people who: (i) have been hospitalized ≥2 times in the last 90 days; (ii) are long-term residents of nursing homes or chronic care facilities; (iii) have received intravenous therapy (antibiotics, chemotherapeutic drugs) and wound management in the last 30 days; and (iv) are receiving dialysis treatment in hospitals or hemodialysis clinics [6,7].
In recent years, a consensus has gradually emerged that the point of differentiation between community-associated and hospital-associated MRSA pneumonia is not the leukocidin (PVL) gene, but the site of pathogenesis. However, due to the constant movement of patients and pathogens between hospitals and the community, CA-MRSA can be brought into hospitals by patients and can lead to nosocomial outbreaks, and HA-MRSA can be brought into the community by MRSA-infected or colonized patients and cause transmission, the distinction between community- and hospital-acquired strains of MRSA is becoming increasingly blurred, and it is difficult to distinguish between the two only clinically and epidemiologically, so it has been advocated to adopt the names of community-onset MRSA (Community Onset-MRSA, CO-MRSA) and hospital-onset MRSA (Hospital Onset-MRSA, HO-MRSA), without emphasizing the differences in strain phenotypes [8,9].
[Diagnosis].
Staphylococcus aureus in the respiratory tract can be asymptomatic and parasitic or can cause severe pneumonia, and the outcome depends on the interaction between the patient, the environment, and the bacteria.
People with any of the following conditions should be alerted to CA-MRSA causing CAP: infants <2 years of age, athletes involved in close physical contact sports (e.g., rugby), injecting drug users, men who have sex with men, those in military service, people living in correctional institutions, residential homes, or shelters; livestock and pet owners and farmers who raise pigs; known CA-MRSA parasites or a recent history of travel to endemic areas with a history of recent contact with CA-MRSA-infected or parasitized individuals; belonging to populations associated with increased rates of CA-MRSA parasitization; complications of influenza or post-influenza pneumonia; and a previous history or family history of recurrent boils or skin abscesses (≥2 occurrences in the past 6 months) [4].
CAP due to CA-MRSA infection commonly presents as follows: it occurs in healthy young adults, mostly with influenza-like prodromal symptoms; it can quickly present with severe respiratory symptoms, including hemoptysis, hypotension, and hyperthermia (temperature >39°C); it presents with rapidly progressive pneumonia and progresses to acute respiratory distress syndrome (ARDS); it has markedly elevated or decreased white blood cells and elevated CRP; chest radiographs show multilobar infiltration and may have cavitation. Some patients may develop septic shock, respiratory failure, or even require admission to the ICU for ventilation and circulatory support [4,5,8].
Chest imaging changes in Aureus pneumonia are not specific. The early manifestations of S. aureus CAP are small focal infiltrates but can progress rapidly within hours and can be unilateral solid or bilateral infiltrates. In contrast to HA-MRSA pneumonia, CA-MRSA often has PVL, so post-infection lung imaging may also show cavitation, as well as pleural fluid, pneumothorax, and pneumothorax. However, in HA-MRSA pneumonia and VAP, the imaging features lack these characteristic features, and MRSA infection should be considered when the patient’s disease is very severe, the imaging changes progress rapidly, and the response to appropriate antibiotic therapy is delayed.
A definitive diagnosis of aureus pneumonia requires an etiologic basis. Culture results of tracheal secretions are less informative for diagnosis than bronchoalveolar lavage fluid. Non-tracheoscopically guided blinded bronchoalveolar lavage is recommended to establish a microbiologic diagnosis, with the advantages of rapid, less costly, and less invasive diagnosis. Blood cultures have a high diagnostic value for secondary pneumonia, such as a high positive rate for pneumonia secondary to infective endocarditis and intervertebral discitis (90%), but not for primary pneumonia (20%). blood cultures are more positive in patients with VAP (24%-36%) than in patients with HAP (5%-15%). Since S. aureus is often present in the upper respiratory secretions of normal individuals and blood cultures of patients often show negativity, it is important to adequately obtain respiratory specimens other than sputum (e.g., endotracheal specimens or pleural fluid) before applying antibiotics for a definitive diagnosis.
The isolated bacteria should be identified on the basis of drug sensitivity tests to distinguish methicillin-sensitive staphylococcus aureus (MSSA) from MRSA, which is important because the choice of antibiotic can determine the effectiveness of clinical treatment. HA-MRSA is not only methicillin- and all β-lactams, but also to many other antibiotics. CA-MRSA, on the other hand, is usually resistant only to β-lactams and is sensitive to most other antibiotics. It is important to note that over time, CA-MRSA can acquire the resistance gene of HA-MRSA, and then conventional antibiotic susceptibility tests will be difficult to distinguish [4,5].
[Empirical treatment indications].
1. CAP: Generally, empirical antimicrobial therapy for CAP is said to target Streptococcus pneumoniae, Haemophilus influenzae, and atypical pathogens. Drawing on international experience, empirical anti-MRSA therapy is recommended for patients hospitalized for severe CAP with risk factors for CA-MRSA infection until sputum and/or blood culture results are available, and severe CAP is defined as pneumonia with one of the following conditions: (i) the need for ICU admission; (ii) necrotic or cavernous infiltration on chest imaging; and (iii) the presence of a pus-filled chest [1].
2. HAP: In recent years, the epidemiology of HA-MRSA has changed: first, the proportion of infections caused by MRSA is increasing, second, the number of patients requiring ventilatory support is increasing, and VAP caused by MRSA has a worse prognosis. Therefore, additional anti-MRSA therapy should be considered in patients with pneumonia who have the following risk factors: (i) prolonged hospitalization, especially prolonged ICU stay, or patients from nursing homes or long-term care facilities, or who have been hospitalized ≥2 times in the last 90 days, as well as those receiving chemotherapy, dialysis, and wound management in outpatient settings; (ii) age ≥65 years; (iii) late onset VAP, especially mechanical ventilation for ≥7 days; (iv) history of receiving history of antimicrobial drug treatment, especially the application of third-generation cephalosporins or fluoroquinolones; ⑤ Influenza, diabetes, renal failure, cranial trauma, coma complicated by pneumonia; ⑥ Gram-positive cocci seen on smear microscopy of lower respiratory secretions; ⑦ Severe sepsis or septic shock [6,10].
[Antimicrobial drug therapy].
Vancomycin, teicoplanin, linezolid, and clindamycin alone, as well as with rifampin and sulfamethoxazole in different combinations and doses, have been used with varying degrees of success in the treatment of MRSA pneumonia.
For HA-MRSA or HCA-MRSA pneumonia, or CA-MRSA pneumonia, intravenous treatment with vancomycin, desmethylvancomycin, teicoplanin, and linezolid is recommended. Dosage and Administration: ① Vancomycin: Adult dose: usually 1 g (or 15-20 mg/kg) intravenously, q12h, requiring a trough concentration of 15㎍⁄ml to 20㎍⁄ml, especially for the treatment of HAP (including VAP). The US IDSA clinical practice guidelines recommend that for patients with normal renal function, a dose of 15 to 20
mg/kg/dose (actual body weight), with a single dose not exceeding 2 g, q8-12h; for severe infections, a loading dose of 25-30 mg/kg (actual body weight) may be given for the reference of fellow patients. Children’s dose: 40 mg/kg/d, intravenous, 4 months~5 years, divided, q6h; 2~18 years, divided, q8h; or 15 mg/kg/d, intravenous, q6h. Vancomycin trough concentration is the most accurate and practical method to guide dose adjustment, and the blood trough concentration should be measured in the steady state of blood concentration before the 4th or 5th dose when available. ②Ticoranine: adult dose: loading dose 400 mg (or 6 mg/kg), intravenous, q12h, first 3 doses; maintenance dose 400 mg (or 6 mg/kg), intravenous, qd. pediatric dose: children over 2 months, loading dose 10 mg/kg, intravenous, q12h, first 3 doses; maintenance dose: severe infection and neutropenia 10 mg/kg, 6 mg/kg for moderate infection, intravenous or intramuscular, qd. Infants less than 2 months: 1st d loading dose of 16 mg/kg, one dose only; maintenance dose: 8 mg/kg, qd, intravenous drip for not less than 30 minutes. (iii) Linezolid: adult dose is 600 mg intravenously or orally, q12 h. In children under 12 years of age, the dose is 10 mg/kg intravenously or orally, q8 h. The total dose does not exceed 600 mg/dose [1,11].
The duration of treatment is 7-21 d depending on the severity of the infection, but moderate to severe pneumonia usually requires a duration of 2-3 weeks, with a maximum of 28 d. If endocarditis and/or osteomyelitis are also present, the duration of treatment requires 4-6 weeks. It is worth noting that our MRSA isolates are mainly HA-MRSA isolates, which have a high resistance rate to erythromycin and clindamycin and are not recommended for the treatment of MRSA infection [1,6].
In patients with MRSA pneumonia complicated by septic chest, anti-MRSA therapy should be accompanied by chest drainage. Nutritional support and symptomatic management are also very important for treatment.
The results of a recent meta-analysis showed no significant differences between linezolid, vancomycin, and teicoplanin in the treatment of MRSA pneumonia, including clinical cure rates, microbial clearance, and overall morbidity and mortality rates.
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