I. Overview
Since the increase of drug resistance in Enterobacteriaceae in the 1970s, new broad-spectrum antibiotics have been widely used, and by the 1990s multidrug-resistant non-fermentative Gram-negative bacilli began to become important pathogens of hospital infections and increased rapidly, among which Acinetobacter is of particular concern for its extreme environmental adaptability and ability to acquire exogenous drug resistance genes and disseminate. Thus, it is called the “methicillin-resistant staphylococcus (MRSA)” among gram-negative bacteria in the 21st century.
Epidemiology
Acinetobacter baumannii, or Acinetobacter baumannii-calcium acetate complex, accounts for 80%-90% of Acinetobacter baumannii, and is the main group of Acinetobacter baumannii causing human infections, which can lead to respiratory tract infections, sepsis, urinary tract infections, meningitis, peritonitis, etc., with pneumonia being the most common. showed that 80.6% of A. baumannii came from respiratory specimens, proving that the most common site of infection for nosocomial infections with A. immortalis is lung infection [1]. A. baumannii is an important causative agent of hospital-acquired pneumonia (HAP), especially in ICU units and/or in patients with mechanical ventilation leading to ventilator-associated pneumonia (VAP). National Nosocomial Infections Surveillance (NNIS) data from 1986-2003 showed that the proportion of HAP caused by Acinetobacter baumannii increased from 4% in 1986 to 7% in 2003 [2]. The Clinical Isolates Resistance Surveillance (CHINET) in 14 different regional hospitals in China showed that the proportion of immobile bacilli to gram-negative bacteria is likewise increasing year by year (12% in 2005 to nearly 16% in 2009) [3]. Recent studies in mechanically ventilated patients and patients with strict collection of non-contaminated specimens using fiberoptic bronchoscopy have confirmed that immobile bacilli account for 15% and 24% of all pneumonia (cases) pathogens, respectively, suggesting that immobile bacilli infections are becoming a prominent complication in mechanically ventilated patients, and it is thought-provoking that this increase is occurring at a time when the management of mechanical ventilation and the sterilization of respiratory therapy instruments have greatly today.
The global surveillance data on bacterial resistance (SENTRY) for Bacteroides immobilis is in the fifth place of HAP causative agents, accompanied by a yearly increase in resistance to commonly used antimicrobial drugs [4]. Drug resistance surveillance at 76 medical centers in the United States from 2004-2005 showed that multidrug-resistant Acinetobacter baumannii (MDRAB) accounted for 29.3% of clinical isolates of Acinetobacter baumannii [5]. The 2009 surveillance data from CHINET in China showed that the resistance rates of the genus Immunobacterium (86.8% of A. baumannii) to imipenem and meropenem were 50.0% and 52.4%, respectively, exceeding those of P. aeruginosa (30.5% and 25.2%, respectively), and the number of pan-resistant strains in A. baumannii increased significantly compared with 2008 (from 10.9% in 2008 to 17% in 2009) [3].
The incidence of mixed infections with A. baumannii is as high as 57%, often mixed with Staphylococcus, Pseudomonas aeruginosa and Enterobacteriaceae [6]. The high morbidity and mortality rate of B. immortalis infection is serious.
Third, bacteriology and drug resistance mechanism
B. immobilis belongs to non-fermentable sugar bacteria, Gram-staining negative cocci, which can be divided into at least 29 genomes. The vast majority of immobile bacteria isolated in clinical specimens are A. baumanii, and it is difficult to distinguish A. baumanii, A. calcoaceticus, A. immobileus genotype 3 and A. immobileus genotype 13TU in routine tests, so they are collectively referred to as the A. baumanii-calcoaceticus complex. Currently, clinical microbiology laboratories need to identify immobile bacilli to the level of species. From the point of view of hospital infection control, it is necessary to distinguish the A. baumannii group from other immobile bacteria because the latter are not very significant for infection control and they are sensitive to many antibiotics. At the same time, the identification of A. baumannii to species is necessary to study the epidemiology, pathogenicity and clinical significance.
A. baumannii has the ability to acquire resistance genes from other species of bacteria and can have its own resistant subgroups that can become prevalent resistant strains under antibiotic pressure screening [8]. Acinetobacter baumannii shows multi-drug resistance to currently used clinical antimicrobial drugs or even pan
Drug Resistant (PDR) phenomenon. The main mechanisms of drug resistance in A. baumannii are: production of hydrolytic enzymes (e.g., β-lactamase) that disrupt the β-lactam ring of antibiotics in a hydrolytic or non-hydrolytic manner to inactivate the antibiotics; alteration of target proteins (e.g., reducing the affinity of penicillin-binding proteins) to inactivate the antibiotics; alteration of outer membrane permeability (e.g., changing its own structure and the number of pore proteins) to reduce antibiotic entry; enhancement of efflux pump activity to make the concentration of antibiotics in the bacteria further decreases.
Carbapenem-resistant Acinetobacter baumannii (CRAB) is one of the most effective antibacterial drugs for the treatment of Acinetobacter baumannii, but in recent years, due to the massive use of this drug in clinical practice, Carbapenem-resistant Acinetobacter baumannii (CRAB) is also gradually increasing, which brings great difficulties to clinical treatment. The main mechanisms of CRAB resistance are also the above four points, among which the production of carbapenemases and loss of outer membrane proteins together are the most important mechanisms of bacterial resistance. The coding sequences of acquired carbapenemases are localized on transferable genetic elements such as plasmids and integrons, and can be transmitted laterally among bacteria, most notably including class B enzymes (metallo-β-lactamases) and class D enzymes (benzocillinases). OXA-23 in benzocillinase is the most predominant carbapenemase in our CRAB.
IV. Susceptibility factors and clinical features
Susceptibility factors for B. immobilis HAP include prolonged stay in ICU wards, mechanical ventilation, tracheotomy, long-term use of triple cephalosporins or carbapenem antibiotics, being in the same ward with patients already infected with B. immobilis, and negligent environmental and hand cleaning by staff [7].
Inactive bacillus pneumonia occurs mainly in patients with mechanical ventilation in ICU wards, and patients infected with Inactive bacillus have significantly longer ICU admissions and ventilation times than patients infected with other gram-negative bacteria or uninfected. The clinical prognosis of ventilator-associated Bacteroides immobilis pneumonia varies widely. A recent study showed that mortality was higher in multidrug-resistant immobile bacilli infections than in patients with sensitive or uninfected organisms; further analysis of the severity of the disease and the underlying disease showed that the difference was the prolonged length of hospitalization and ICU stay after infection with multidrug-resistant immobile bacilli [6].
The clinical features of CAP due to Acinetobacter baumannii are the usual colonization of the oropharynx by the pathogen, the rapid progression of pneumonia, and the high mortality rate associated with a history of alcohol abuse and neoplasia. Acinetobacter baumannii pneumonia occurs mostly in the summer months and may be associated with high temperatures and humid environments.
V. Diagnosis
The confusion in the clinical diagnosis of A. baumannii pneumonia is: how should the A. baumannii isolated from sputum or transtracheal aspiration specimens (TTA) be distinguished as a colonizing or infecting organism? One study confirmed that the positive rate of hospitalized patients’ pharyngeal swab cultures for A. baumannii spp. ranged from 7% to 18%, while tracheotomy trocar swabs were as high as 45%. Distinguishing between colonization and infection is very important for the rational use of antibiotics, and this is precisely the challenge that has not been solved so far in respiratory tract infection clinics. At the current level of knowledge, the need for antibiotic therapy in patients with immobile bacilli isolated from respiratory specimens should be based on (i) clinical signs, symptoms, and imaging of new, or persistent, or exacerbated pulmonary exudates, infiltrates, or solid lesions consistent with pneumonia; (ii) host factors such as underlying disease, immune status, prior antibiotic therapy, other risk factors associated with morbidity such as mechanical ventilation time, etc.; ③ patients who are receiving antibiotic therapy if once improved, and then aggravated, in time with the emergence of immobile bacilli; ④ from the specimen collection method, specimen quality, bacterial concentration (quantitative or semi-quantitative culture), smear seen, etc., to evaluate the clinical significance of positive culture results.
VI. Treatment
1. Principles of antibiotic treatment for Acinetobacter baumannii.
(1) According to the results of drug sensitivity test, the choice of antibacterial drugs: Acinetobacter baumannii resistance rate of most antibacterial drugs reached 50% or more, empirical selection of antibacterial drugs is more difficult, so should be based on the results of drug sensitivity selection of sensitive drugs;
(2) to carbapenem resistance, especially extreme drug resistance (Extensive Drug
Resistant (XDR) or PDR strains of infection, recommended combination therapy based on sulbactam or sulbactam-containing combination;
(3) Higher doses and longer duration of treatment are usually required;
(4) The culture of Bacteroides immobilis in respiratory secretions should determine whether the infection is parasitic or infectious, if only culture results without clinical symptoms or imaging evidence can temporarily do not need anti-infective treatment. The tracheal intubation should be removed as soon as possible, and if necessary, a non-invasive ventilator can be used to assist breathing.
(5) If the bacterial culture is free of pathogenic bacterial growth (true negative), descending step therapy or discontinuation of antibiotics should be performed.
2. Characteristics of antibacterial drugs commonly used in the treatment of Acinetobacter baumannii.
(1) Sulbactam and sulbactam-containing β-lactamase inhibitor combination: 2009 CHINET bacterial resistance showed that cefoperazone/sulbactam has the lowest resistance rate among the antimicrobials currently in clinical use in China. Sulbactam and sulbactam combination have good antibacterial activity against Fusobacterium spp. At present, there is no separate preparation of sulbactam in China, and the combination containing sulbactam can be used, mostly cefoperazone/sulbactam, and also ampicillin/sulbactam.
(2) Carbapenems: strong antibacterial activity against sensitive strains of Fusobacterium, and can be used for multi-drug resistant bacterial infections. However, the resistance of A. baumannii to carbapenems has increased rapidly in recent years, and the resistance rate is around 50% worldwide (including China), and imipenem and meropenem are commonly used.
(3) aminoglycosides: mostly combined with other antibacterial drugs for the treatment of sensitive immobile bacilli infections, the current resistance rate of Acinetobacter baumannii to amikacin in China is nearly 50%.
(4) Polymyxin class: the clinical application is mostly polymyxin E, and the resistance rate of A. baumannii to it is low.
(5) Tigecycline: It is the first glycylcycline antibiotic approved for marketing, and in vitro experiments have been found to have good antibacterial activity against carbapenem-resistant immobilized bacilli. However, there is insufficient experience in clinical application, and good efficacy has been reported in small samples used to treat patients with severe VAP. It is noteworthy that in vitro experiments have found the emergence of resistant strains [9], and for severe infections often need to be combined with other antibacterial agents.
3. Selection of antibacterial drugs for A. baumannii.
(1) Non-multiple drug resistant A. baumannii can be used with sensitive broad-spectrum cephalosporins, β-lactam-β-lactamase inhibitor complexes (especially containing sulbactam), or carbapenems.
(2) MDR strains should be used β-lactam complex containing sulbactam, or carbapenems.
(3) CRAB infection is mostly used in combination antimicrobial therapy regimen, sulbactam or sulbactam-containing β-lactam complex, polymyxin or tigecycline .
VII. Prevention
The most important measure to control inactive bacillus pneumonia is to prevent outbreaks of epidemics of inactive bacilli in health care facilities. Examples include prevention of contamination of humidifiers, aspirators and furniture, blood pressure cuffs, attention to hand cleanliness of medical staff, bedside isolation and disinfection of susceptible patients, attention to cleanliness during medical invasive operations, screening and decolonization, antibiotic administration, etc.