Klebsiella pneumoniae, also known as S. pneumoniae or Friedlander’s bacillus, was the first gram-negative bacillus recognized to cause pneumonia. The symptoms are sudden, with chills, high fever, cough, pus sputum, and characteristic brick-red jelly sputum. 80% of patients have chest pain, mainly due to inflammation invading the mural pleura. Some patients have gastrointestinal symptoms, such as nausea, vomiting, diarrhea, jaundice, etc. The whole body is debilitated, and some patients see symptoms of upper respiratory tract infection. Very few patients present with a chronic course or can be extended from an acute course. The presentation is characterized by low-grade fever, cough, and weight loss. Signs acute illness appearance, dyspnea, cyanosis, jaundice and shock may occur in a few patients.
Overview.
Klebsiella pneumoniae, gram-negativebacillarypneumonia (GNBP) was once thought to be a very rare disease that received little clinical attention. With the exception of Klebsiella, there have been few reports of pneumonia caused by gram-negativebacterium (GNB). With the change of the susceptible population, the widespread use of antimicrobial drugs and the change of drug-resistant bacteria, as well as the improvement and popularity of various microbiological detection techniques, GNBP has become an important disease in modern medicine in the era of antibiotics. the proportion of GNB in the pathogen of pneumonia has increased from 0.5%-5.0% to 9%-37% of community-acquired pneumonia and hospital-acquired pneumonia ( Nosocomial pneumonia (NP) accounts for more than 70% of all cases. Much research has been conducted in the areas of clinical and epidemiological features, susceptibility factors, pathogenic diagnosis, and anti-infective therapeutic agents and methods for hospital- and extra-hospital-acquired GNBP, but the morbidity and mortality rates remain high. The study and summary of GNBP pathogenesis and diagnosis and treatment experience are still important topics in the field of pulmonary infectious diseases for some time in the future. Meta-analysis shows that the overall incidence of pneumonia in hospitals in China is 2.33%, while S. pneumoniae accounts for 10.1% of all pathogens of pneumonia in hospitals. Although there are many prospective and retrospective surveys, the exact incidence of S. pneumoniae pneumonia in the social population is difficult to estimate, and there is a decreasing trend in the clinical isolation rate of S. pneumoniae.
Signs.
1, the symptoms start suddenly, chills, high fever, cough, pus sputum, brick-red jelly sputum is characteristic. 80% of patients have chest pain, mainly due to inflammation invading the wall pleura. Some patients have gastrointestinal symptoms, such as nausea, vomiting, diarrhea, jaundice, etc. The whole body is debilitated, and some patients see symptoms of upper respiratory tract infection. Very few patients present with a chronic course or can be extended from an acute course. The manifestations are low fever, cough and weight loss.
2.Signs of acute illness, dyspnea, cyanosis, jaundice and shock may occur in a few patients. Wet woven leukocytes and neutrophilia can be heard in the lungs, and sputum culture is positive.
Etiology.
Bacillus pneumoniae is Gram-stain negative, inactive, podulated, paired or in short chains, and grows easily on normal media. In solid medium colonies above the surface, smooth and sticky wet is its characteristic. According to the different components of podocyte antigen, S. pneumoniae can be divided into 75 subtypes, causing pneumonia to 1 to 6 types are mainly, can quickly adapt to the host environment and long-term survival, to a variety of antibiotics are prone to resistance. Pneumococcal pneumonia is mostly seen in middle-aged and elderly people, and any situation that leads to impaired immune function of the body can be a trigger for the infection. For example, hormones and immunosuppressive drugs, as well as the use of anti-metabolic drugs causing systemic immune dysfunction and various serious diseases (such as tumors, diabetes, chronic liver disease, leukopenia, leukemia, etc.); certain invasive examinations, traumatic treatment and surgery, the use of contaminated respirators, nebulizers, etc. have the potential to cause the onset of infection. Hand transmission by hospital staff, patients and chronic disease carriers are sources of germs.
Physiology.
1, susceptible populations Klebsiella pneumoniae pneumonia is an opportunistic infectious disease, its occurrence and development are dependent on a certain pathological basis, common susceptibility factors include: (1), patients with chronic diseases: common are long-term alcoholics, diabetes, chronic heart and lung disease, cancer and leukopenia patients. (2), those who apply multiple antibiotics, glucocorticoids, immunosuppressive drugs and cytotoxic drugs for long-term treatment. (3).Patients treated in intensive care unit (ICU) for a long time, including post-surgical care patients and people with advanced neuromuscular diseases, etc. (4), Patients who apply respiratory therapy devices. Such as the application of mechanical ventilation, nebulization therapy, etc. NP in such patients is the focus of attention from all sides, and its morbidity and mortality rates are much higher than the average of Klebsiella pneumoniae pneumonia.
2, the source of germs The main sources of germs are patients and chronic carriers of germs (such as chronic alcoholics), the spread of bacteria are mainly the following ways.
(1), hand transmission by hospital staff, home care workers and other related personnel: the main reason is that the preventive measures of disinfection and cross-infection are not strictly implemented.
(2), device transmission: common include nebulizer, ventilator and its pipeline, tracheal intubation, nasal feeding tube, etc.
(1) Nebulizer: It is a common source of infection and can lead to environmental contamination in addition to cross-infection. Merlz reported that the fulminant Klebsiella pneumonia that occurred in Bilevui Hospital was caused by nebulizer contamination. ② ventilator: mechanical ventilation process, because the pipeline and the patient’s airway connected to form a closed loop, coupled with environmental pollution, sterilization is not strict, not timely tube replacement and other factors, so that the pipeline colonization rate is very high, while the gas compression and pipeline and the temperature difference between the surrounding environment, resulting in water and gas condensation in the pipeline (especially at the tracheal cannula). It is reported that the water and gas condensation volume of ordinary unheated pipeline reaches 20-40ml per hour, which is the main place for bacteria to survive. It is reported that the water in the line near the intubation place contains more than 200,000 bacteria per ml, and turning the patient’s body position, etc. will cause the bacteria-containing water to flow directly into the lower respiratory tract. At present, there are few autonomous heating lines, and they are expensive and cumbersome to maintain, making an immediate solution difficult. According to the requirements of the Centers for Disease Control (CDC), the line should be replaced every 24h, but clinical practice has found that there is no difference in the number of bacteria between the two compared with 48h replacement of the line, and some literature even points out that the incidence of pneumonia is higher with every 24h replacement of the line. The specific needs of the clinic depends on the monitoring results and actual conditions. According to the relevant literature, the incidence of pneumonia in patients receiving mechanical ventilation is 7-21 times higher than in those who do not receive it, with Klebsiella pneumoniae being one of the most common pathogens. ③ tracheal intubation: tracheal intubation is a colonization-intensive device, according to an electron microscopic examination, 95% of the area of the intubation can be seen as colonies, 86% of which are completely covered by colonies. the reasons for this are: A. the intubation damages the pharynx and destroys the natural defense mechanism of the host. b. it destroys the cleaning effect of the airway cilia. c. it destroys the swallowing reflex and activity. d. the intubation cannot be changed frequently and the sputum is mixed inside and outside during aspiration infection. In view of the above reasons, tracheal intubation and direct crossing of the pharyngeal barrier, coupled with leakage of secretion around the capsule, allow bacteria to enter the lower airway directly.
(3), pharyngeal colonization: the pharynx is the most common site of colonization of Klebsiella pneumoniae, but also the direct source of pneumonia. The detection rate of Klebsiella pneumoniae in the pharynx of normal people is less than 1%, while in critically ill patients, Gram-negative bacilli are detected up to 70% by repeated culture of pharyngeal secretions. In one study, 22 of 26 patients (84%) with nosocomially acquired Klebsiella pneumoniae pneumonia in an ICU had prior pharyngeal detection of Klebsiella pneumoniae. Colonization of the pharynx is closely related to the adsorption capacity of pharyngeal epithelial cells. On the surface of pharyngeal epithelial cells, there are corresponding bacterial adsorption receptors, which are normally covered by pharyngeal fibronectin, but in pathological conditions (alcohol abuse, nutritional imbalance, smoking, application of broad-spectrum antibiotics and tracheal intubation), various non-specific proteases are released into the oral cavity, which can digest the fibronectin on the surface of epithelial cells, and at this moment the receptors At this moment, the receptor is revealed, and the bacteria will “chain-like” adsorption with it. Klebsiella pneumoniae has a very high affinity for pharyngeal epithelial cells. Curiously, it does not have a brush border for adsorption purposes, so the principle of adsorption is not known. The oropharyngeal survival of Klebsiella pneumoniae can often be several months, and this is particularly evident in patients with chronic alcoholism, where it is estimated that about 29% of chronic alcoholics are pharyngeal Klebsiella pneumoniae carriers. According to a follow-up survey on the pharyngeal bacteria of patients discharged from the hospital after recovering from pneumonia: more than 75% of patients discharged from the hospital 4 weeks after the disappearance of pharyngeal colonies (including Pseudomonas aeruginosa, Staphylococcus aureus, etc.), but most of the Klebsiella pneumoniae persisted, to the end of the survey, there are still 43% of Klebsiella pneumoniae colonies have not disappeared. Factors affecting the colonization of pharyngeal Klebsiella pneumoniae are: ① changes in the host cells: various receptors on the host epithelial cells each accept the corresponding bacteria, and the application of cyclosporine A inhibits the ability of the receptors to adsorb Klebsiella pneumoniae. (ii) Changes in bacteria: This includes whether the bacteria themselves have podocytes, the type of surface adsorbates and the characteristics of external contact release, etc. The surface adsorbates of Klebsiella pneumoniae are not known. ③Changes in the local microenvironment: the pH value in the environment has the greatest influence. When pH 6,5-7,2, the adsorption capacity of bacteria can dramatically increase to the highest level. In addition, the increase of mucin and protease concentration in sputum and oropharyngeal secretions and the decrease of IgA level can enhance the adsorption capacity. Inappropriate application of antibiotics, eliminating the inhibitory flora of gram-negative bacilli in the pharynx (such as streptococci), can also increase their colonization and growth. (4) Stomach colonization: Normal stomach remains sterile due to the acidic barrier. Studies have shown that changes in the gastric environment can also cause colonization, and become an important source of pharyngeal transplantation of intestinal resident bacteria such as Klebsiella pneumoniae. The pathological conditions that cause the increase of gastric colonization are: (i) old age and decrease of various functions of the stomach itself. ② Lack of gastric acid and loss of acid barrier. (iii) Various acute and chronic gastrointestinal diseases. ④Nutritional imbalance. ⑤ Application of antacids and/or H2 receptor antagonists. When there is a lack of gastric acid or elevated pH, the number of bacteria in gastric juice can be as high as 1 million to 10,000,000 per milliliter, which, together with abnormal reflexes, can cause gastric colonies to reflux to the pharynx and form pathogenic bacteria for pneumonia and bronchitis. Studies have shown that Klebsiella pneumoniae is rarely present when the pH of gastric juice is <3. According to deFrock et al. it was demonstrated that the pathological situation is associated with the emergence of new colonies of gram-negative bacilli in the pharynx with bacteria previously found in the stool, and that as the colonies in the stool change during hospitalization, the pharyngeal colonies change accordingly. after selective decontamination of the digestive tract by McAedingham, it was found that the rate of respiratory infections was six times lower in the disinfected group than in the control group, and pharyngeal and rectal colonies were significantly were reduced. To prevent stress ulcers in critically ill patients after the application of antacids and (or) H2 receptor antagonists, secondary to increased pharyngeal colonization, so that the increase in respiratory tract infections, has been confirmed by numerous clinical studies.
3, the lung’s own defense mechanism when K. pneumoniae enters the alveoli, the lung’s own defense phagocytic system first self-defense to stop the infection. Rehm et al. showed that neutrophil-deficient mice could quickly clear Staphylococcus aureus from the alveoli, but not Klebsiella pneumoniae. It was shown that the tiny pods of Klebsiella pneumoniae prevented phagocytes from entering within the central region of the infection. From the animal model of Klebsiella pneumoniae pneumonia, it can be found that the main reason for the pathogenicity of the thick podococcal strain is its resistance to phagocytosis in animals. When the bacteria invade the alveoli, the alveolar cavity is filled with a large number of neutrophils, and the process of phagocytosis of K. pneumoniae by PMN in the alveolar cavity can be observed through microscopy. Due to the stimulation of a variety of lymphatic chemokines in the lung by the bacteria, chemokines are released into the alveoli, which induce PMN to continuously replenish the alveolar cavity from the circulation. It is the role of non-complement chemokines.
4, the pathogenesis of endotracheal inhalation (aspiration) is the key to the development of pneumonia. 70% of normal people can be aspirated during sleep, but whether the aspiration is pathogenic, the key is to reach a certain concentration of pharyngeal bacterial inhalation, research shows that the pharynx Gram-negative bacilli colonization is a sign of defective autonomic defense of the respiratory tract in critically ill patients, once the bacteria inhaled lower respiratory tract, can develop into pneumonia. In addition, in addition to dense pharyngeal colonization, the following factors can also increase airway aspiration: ① confusion or coma. (ii) Abnormal sphincter function reflexes. (iii) Delayed gastric emptying and reduced activity. ④Swallowing malfunction. ⑤Leakage of bacteria around the tracheal intubation sleeve, etc.
5, pathological changes primary Klebsiella pneumoniae pneumonia mostly with large lobe distribution, commonly in the upper lobe of the lung, especially the right upper lobe; secondary pneumonia mostly with small lobe distribution, as bilateral lung patchy bronchopneumonia-like manifestations, multi-lobe, bilateral and small lobe distribution is rare, the overall pathology is similar to pneumococcal pneumonia, but the development is faster, no obvious pneumonia stage changes, but has its own characteristics: ① autopsy lesion lung lobes. Its cut surface can see mucus-like exudate outflow, or can pick up mucousy filamentous exudate, which is the characteristic change of its pathology. (2) Rapid destruction of lung tissue, multiple abscesses or single large abscesses can be formed within 4 days, destruction of alveolar wall, resulting in alveolar atrophy, reduction of lung volume, and embolization of major pulmonary vessels, causing secondary pulmonary gangrene and necrosis. (iii) Pleural invasion is often combined with pleural fibrinous exudation and adhesions, the incidence of which is about 25%, and even combined with pericardial effusion. ④In early histological examination, edema fluid, mononuclear cells and bacteria can be seen, and in later stages, destruction of alveolar wall with a large number of polymorphonuclear neutrophils and active proliferation of fibrous tissue can be seen, which is prone to mechanistic changes. ⑤ It can lead to intrapulmonary hemorrhage, pus pneumothorax, pericarditis, bronchiectasis and other changes, and some of them can become chronic Klebsiella pneumonia changes.
Diagnosis.
Middle-aged and elderly males with long-term alcoholism, chronic bronchitis or other lung diseases, diabetes mellitus, malignancy, organ transplantation or immunosuppression such as granulocytopenia, or patients with constructed artificial airway mechanical ventilation, fever, cough, sputum, dyspnea and wet stalls in the lungs Yue O to strider cherry Min X-ray with inflammatory infiltrative lung manifestations suggestive of bacterial pneumonia should all be considered as possible L. pneumoniae pneumonia. Especially when treatment with penicillin or erythromycin and other macrolide antibiotics is ineffective. The clinical manifestations, laboratory and radiographic examinations of S. pneumoniae pneumonia are mostly non-characteristic. Coughing up brick-red sputum, although typical of its presentation, is uncommon clinically. Microbiological examination is the only basis for confirming the diagnosis of S. pneumoniae pneumonia and is an important method to differentiate it from other bacterial pneumonia.
A smear of a qualified sputum specimen with a high number of gram-negative bacilli, especially a large number of clusters around pus cells and bronchial pseudostratified ciliated columnar epithelial cells with podocytes, should be considered as a possibility of S. pneumoniae pneumonia, but not as a basis for confirmation. Sputum culture isolation of S. pneumoniae is useful for diagnosis, but should be differentiated from contaminating bacteria colonizing the oropharynx. Two or more consecutive sputum specimens isolated with S. pneumoniae by smear screening or sputum quantitative culture isolated with S. pneumoniae concentration > 106 CFU/ml or semi-quantitative concentration of ++++ or ++++ can be proposed as S. pneumoniae pneumonia. In severe, refractory or immunosuppressed cases, the use of anti-pollution lower respiratory tract specimen sampling techniques such as transcircumferential nail puncture tracheal aspiration (TTA), anti-pollution double cannula brush sampling (PSB), bronchoalveolar lavage (BAL) and percutaneous pulmonary puncture aspiration (LA), etc., from which B. pneumoniae are isolated can confirm the diagnosis of the disease. It is important to pay attention to and actively carry out blood or pleural fluid bacterial culture, if positive not only has a definitive diagnosis, but also is important for the selection of sensitive antibacterial drugs and improving the prognosis.
Tests.
1, blood tests most patients have increased blood leukocytes, the range is on average in (150-200) × 109 / L, which has toxic particles and nuclear left shift phenomenon, about 1/4 of patients with normal or reduced total leukocyte count, leukopenia is often a sign of poor prognosis, patients often combined with anemia.
2, sputum or bronchial suction smear and/or culture to detect Klebsiella pneumoniae is the basis for confirming the diagnosis, but it is influenced by many factors.
(1), pathological situation, Klebsiella pneumoniae has a high rate of pharyngeal parasitism, and it is easy to form oropharyngeal specimen contamination. (2), single Klebsiella pneumoniae pneumonia is decreasing, and mixed infections of multiple bacteria are increasing (especially nosocomial infections). It is often impossible to identify the main acting bacteria.
At present, domestic and foreign scholars agree that the sputum test is not ideal in terms of sensitivity, specificity and reliability, many patients do not have much sputum, even if there is sputum sometimes can not detect bacteria, some patients can be identified by culture, but it is not very helpful for the initial diagnosis and treatment. However, as far as the current situation and conditions of hospitals in China are concerned, sputum smear Gram stain and culture is still an important preliminary screening tool and diagnostic measure.
Treatment.
Treatment of S. pneumoniae pneumonia includes anti-infective therapy and supportive therapy. The effectiveness of anti-infective therapy directly affects the prognosis of the disease. Prior to the antibiotic era, the morbidity and mortality rates for S. pneumoniae pneumonia were as high as 51% to 97%. Under antibiotic treatment, the morbidity and mortality rate has decreased significantly, but due to the high rate of resistance of S. pneumoniae, the morbidity and mortality rate is 20% to 30%, which still exceeds that of Streptococcus pneumonia.
There are more drugs with antibacterial activity against S. pneumoniae, including first- to fourth-generation cephalosporins, broad-spectrum penicillins, aminoglycoside antibiotics, fluoroquinolones, carbapenems, and monocyclic β-lactams. Chloramphenicol and tetracycline have antibacterial effects, but there are many drug-resistant strains and little clinical application. High efficiency, low toxicity and low cost are the most important factors for considering the selection of antibacterial drugs. With the expansion of the variety of clinically available drugs and the increasing number of multi-drug resistant strains, a reasonable choice should be based on drug sensitivity tests. Before obtaining the results of drug susceptibility testing, or in units without drug susceptibility testing, or when several antimicrobial drugs tested show resistance, empirical use is the only option for developing anti-infection programs. Empirical drug use should emphasize the selection of drugs in conjunction with the results of previous bacterial resistance surveillance in the region, the unit or even the department.
Second, third or fourth generation cephalosporins or combined aminoglycosides are usually recommended, or cephalosporins alone may be used if drug sensitivity results are available. Commonly used methods: cefotaxime 2g IV every 8 hours or ceftriaxone 2g IV once/d. Amantadine, second generation cephalosporins such as cefuroxime can also be used. In areas where the frequency of antibiotic use is low and drug resistance is not serious, especially for community infections with milder disease, first-generation cephalosporins such as cefazolin and cefradine can be used at a dose of 4-6g/d, divided into 2-4 intravenous drips. The resistance rate of ampicillin among penicillins has been high, but the new generation of broad-spectrum penicillin such as piperacillin has better therapeutic effect on S. pneumoniae pneumonia.
Aminoglycosides optional gentamicin, but there are more resistant strains. Amikacin is now commonly used, and the usual amount is 0,4-0,6g/d, divided into 1 or 2 intravenous drips. Because aminoglycosides do not easily penetrate bronchial mucosa and sputum, the concentration of antibiotics in bronchial secretions is only 5% to 40% of the blood concentration, and the acidic environment of sputum will significantly reduce the antibacterial activity of antibiotics, so the clinical efficacy of aminoglycosides is often inferior to in vitro drug sensitivity tests. Therefore, for pulmonary infections, especially severe infections, aminoglycosides should be used in combination with β-lactams rather than alone. Fluoroquinolones such as ciprofloxacin and levofloxacin, cephalexin such as cefoxitin and cefmetazole, and β-lactam/β-lactamase inhibitor complexes such as sultamicillin (ampicillin/sulbactam), cefoperazone/sulbactam, and piperacillin/clavulanic acid also have good antibacterial activity against S. pneumoniae, including many drug-resistant strains, and are worth using. In some areas, especially in hospital pneumonia, the detection rate of super broad-spectrum β-lactamase (ESBL) producing strains of S. pneumoniae has increased significantly, and ESBL accounts for 20% to 30% of S. pneumoniae in many ICU infection strains. For infections caused by such strains, carbapenems such as imipenem, meropenem, etc. are preferred, and are administered as follows: imipenem 0, 5g intravenously every 8 hours, or 1g intravenously every 12 hours. Cefoperazone/sulbactam also has good antibacterial activity against ESBL strains of S. pneumoniae. The course of anti-infective therapy for S. pneumoniae pneumonia is usually 10 to 14 days, or at least 3 weeks when the lesions are extensive, especially in the presence of multiple small abscesses. Supportive therapy including keeping the airway open, oxygen administration, correction of water, electrolyte and acid-base imbalance, and nutritional supplementation should not be neglected in the treatment of S. pneumoniae pneumonia.
Prevention.
1, strict implementation of disinfection and isolation system This is mainly for medical personnel and the hospital environment, equipment, strict hand washing before and after contact with patients, wearing gloves to operate, regular environmental and indoor disinfection and ventilation, regular cleaning and disinfection of respiratory therapy devices according to requirements, regular replacement of mechanical ventilation and nebulizer lines, etc. A set of strict nosocomial infection monitoring and prevention program is adopted. It was reported that hospitals that adopted this program had a 20% lower rate of nosocomial infections compared to hospitals that did not.
2, gastrointestinal decontamination treatment This is a common preventive measure in Europe, mainly for susceptible people with nosocomial infections, with the aim of removing colonization and growth of bacteria in the gastrointestinal tract. Methods are whole gastrointestinal decontamination and selective gastrointestinal decontamination method, commonly used for the latter, it is through nasal or oral gastrointestinal non-absorption of polymyxin B, tobramycin (gentamicin or neomycin, etc.) and diclofenac B, for 5 days, and daily systemic application of cephalosporins, from the oropharynx and gastrointestinal tract to remove aerobic bacteria without reducing the number of anaerobic bacteria, its preventive effect is particularly obvious in Gram-negative bacilli, according to The authors statistics about the literature, decontamination group almost no secondary pneumonia and respiratory tract infection of Klebsiella pneumoniae (individual infection of drug-resistant strains).
3, protection of the acidic barrier of the stomach is mainly in the prevention of stress ulcers, the application of thioglycollate (ulcerlmin) class of drugs, it can prevent stress ulcer bleeding, but also because it has adsorption of gastric mucosa, change gastric mucus, increase the content of prostaglandin E2 (PGE2) in the gastric lumen, absorption of pepsin, and does not change the acidic environment in the stomach, thus effectively play a role in preventing ulcers and prevent According to the literature, aluminum thioglycollate still has inherent bactericidal activity, and a series of studies have shown that the incidence of pneumonia in the application of antacids group is 23% to 35%, while the incidence of pneumonia in the application of aluminum thioglycollate group is 10% to 19%.
Held et al. used IgM monoclonal antibodies (MAb) induced by Klebsiella pneumoniae podocystis polysaccharide (CPS) from experimental animals to prevent Klebsiella pneumonia, compared with the control group, regardless of the rate of organ involvement, the number of bacteria in the infected tissue, histological changes in the lung, etc. The preventive group was much better than the control group (P < 0,01), but this MAb did not yet prevent Klebsiella pneumoniae from entering the lungs, but rather accelerated the absorption of the infection and enhanced the lung's ability to excrete bacteria. Some other similar experiments have been reported, but mature vaccines and antibodies have not yet been applied clinically and further studies are needed. Klebsiella pneumoniae pneumonia has harmed humans for more than a century. With the development of science, the continuous improvement of examination and treatment methods, and the gradual improvement of human understanding of it, we believe that we can further reduce its incidence and death rate and make more progress.