Leptin corrects host defense defects after acute starvation in murine pneumococcal pneumonia

RATIONALE: Leptin is an adipocyte-derived hormone that declines dramatically during fasting and plays a pivotal role in the neuroendocrine response to starvation. Previously, we employed leptin-deficient (ob/ob) mice to identify an important role for leptin in the host defense against Klebsiella pneumonia. OBJECTIVES: To assess the effects of fasting on the innate immune response against pneumococcal pneumonia and to determine the effects of maintaining circulating leptin levels on host defense in fasted mice. METHODS: C57BL/6 mice were either fed ad libitum or fasted for 48 h and given an intraperitoneal injection of saline or recombinant leptin (1 microg/g of body weight) twice daily for 48 h before bacterial challenge. Mice were challenged with 10(5) cfu of Streptococcus pneumoniae via the intranasal route. MEASUREMENTS AND MAIN RESULTS: Lung homogenate S. pneumoniae burden was nearly 20-fold greater in the fasted as compared with fed mice. The impairment in bacterial clearance observed in fasted animals was associated with reduced bronchoalveolar lavage neutrophil counts and interleukin-6 and macrophage inflammatory protein-2 levels. Alveolar macrophages from fasted animals also exhibited defective phagocytosis and killing of S. pneumoniae and reduced calcium-ionophore-stimulated leukotriene B(4) synthesis in vitro. In contrast, the provision of exogenous leptin to fasted animals restored bacterial clearance, bronchoalveolar lavage levels of neutrophils and cytokines, alveolar macrophage bacterial killing, and leukotriene B(4) synthesis. CONCLUSIONS: These results suggest that reduced leptin levels substantially contribute to the suppression of pulmonary antibacterial host defense during starvation and that administration of this adipokine may be of therapeutic benefit clinically.     

Alveolar macrophage function in a canine model of endotoxin-induced lung injury

Humans with bacterial sepsis are predisposed to acute lung injury with respiratory failure and have an increased risk of pulmonary infection. Because the alveolar macrophage is the resident phagocyte in the lung and a defect in antimicrobial activity could predispose to infection, we assessed the functional integrity of these cells in vitro in a canine model of Escherichia coli endotoxin-induced lung injury with respiratory failure. Dogs were given 2 or 20 mg/kg of E. coli endotoxin 055:B5, and alveolar macrophages from pulmonary lavage were compared with those from control dogs. The physiologic criteria for the adult respiratory distress syndrome and pathologic confirmation of acute lung injury were produced in all endotoxin-treated animals. The production of acute lung injury with respiratory failure by E. coli endotoxin was associated with several alterations in alveolar macrophage function. Adherence was significantly reduced for cells from the endotoxin groups. The alveolar macrophages from endotoxin-treated animals differed from those from control animals, with significantly greater production of hydrogen peroxide, significantly greater peaks in chemiluminescence, significantly reduced phagocytosis of Staphylococcus aureus and E. coli at all times, and a diminished ability to kill cell-associated S. aureus and E. coli over time. These derangements could play a role in the therapeutic failures of pneumonia, an increased risk for nosocomial pneumonias, or the propagation of acute lung injury with respiratory failure.     

Recovery of blood-borne bacteria from human urine

Recovery from the urine of organisms causing bacteraemia may depend on the bacterial species involved. The survival of the more common species of bacteria which cause bacteraemia was examined in human urine, serum and normal saline. All species survived well or grew in serum. Haemophilus influenzae, Streptococcus pneumoniae, Streptococcus sanguis and group A streptococci were killed in all urine samples. The number of colony-forming units of Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus saprophyticus and group B streptococci either remained the same or increased in the urine, while the numbers of Escherichia coli and Klebsiella pneumoniae increased rapidly. These data suggest that the observed differences in recovery from urine of these bacterial species that cause bacteraemia are related to the viability of the species in human urine.     

Ticarcillin: a collaborative in vitro comparison with carbenicillin against over 9,000 clinical bacterial isolates

The minimal inhibitory concentrations of ticarcillin and carbenicillin were determined for 9,236 clinical bacterial isolates by the broth microdilution method at four participating laboratories. Ticarcillin showed significantly increased activity against Klebsiella pneumoniae (P less than .001), Pseudomonas aeruginosa (P less than .001) and Aeromonas hydrophilia (P less than .005) when compared to carbenicillin, but no signifcant differences were observed against other gram-negative organisms. Ticarcillin was consistently less active against the gram-positive cocci, and these differences were significant for Staphylococcus aureus (P less than .001), Streptococcus agalactiae (P less than .001), Staphylococcus epidermidis (P less than .001) and Streptococcus viridans (P less than .005). Significant regional and institutional differences in susceptibility to the two drugs were observed for several species, including common nosocomial pathogens such as S. aureus, P. aeruginosa, K. pneumoniae and Escherichia coli.     

Phagocytosis and killing of common bacterial pathogens of the lung by human alveolar macrophages

To investigate factors that determine susceptibility of the lungs to infection with common respiratory pathogens, we studied phagocytosis and killing of nontypable Haemophilus influenzae, H. influenzae type b, Streptococcus pneumoniae types III, VI, and XIV, an unencapsulated variant of S. pneumoniae type III, and Staphylococcus aureus Cowan I, by using human alveolar macrophages obtained by bronchoalveolar lavage of healthy nonsmokers. After opsonization with 10% pooled human serum, mean uptake (+/- standard deviation) of nontypable H. influenzae (67.5% +/- 15.0%), unencapsulated S. pneumoniae type III (71.2% +/- 4.8%) and S. aureus (79.1% +/- 10.2%) was significantly greater (P less than .01) than that of H. influenzae type b (40.1% +/- 15.0%), and S. pneumoniae types III (4.4% +/- 3.1%), VI (11.8% +/- 9.6%), or XIV (8.7% +/- 7.0%). Nontypable H. influenzae was ingested after opsonization with much less pooled human serum than was H. influenzae type b, and uptake of encapsulated S. pneumoniae was not enhanced by as much as 80% pooled human serum. Intracellular killing of unencapsulated S. pneumoniae type III and nontypable H. influenzae was rapid and complete and corresponded to the degree of phagocytosis, but despite a high uptake, S. aureus were killed slowly and incompletely. The virulence of S. pneumoniae and H. influenzae as lung pathogens is thus determined jointly by encapsulation and the inadequate opsonizing effect of normal human serum, whereas that of S. aureus may be related to the organism's relative resistance to intracellular killing by alveolar macrophages.     

Kinetics of phagocytosis and bacterial killing by human polymorphonuclear leukocytes and monocytes.

The kinetics of phagocytosis and bacterial killing by normal human polymorphonuclear leukocytes (PMNLs) and by monocytes (MNs) were compared by use of [3H]thymidine-labeled Staphylococcus aureus, Escherichia coli, and Listeria monocytogenes. The rate of phagocytosis by PMNLs was approximately twice that by MNs for all three bacterial species. Although a marked difference was found in opsonic requirements for phagocytosis of S. aureus, E. coli, and L. monocytogenes, phagocytosis by PMNLs and MNs was mediated via the same serum factors. All three species were killed rapidly once they were associated with leukocytes; however, the rate of killing by MNs was slower than that of PMNLs. The slower rate of killing appeared to be secondary to slower ingestion of attached bacteria by MNs. Thus, PMNLs and MNs appear to possess receptors with specificity for the same bacterial opsonins; however, PMNLs are capable of more efficienct bacterial phagocytosis (attachment and ingestion) than are MNs.     

Life in the allogeneic environment after lung transplantation

Because infection and rejection are the principal complications of any transplant procedure and because the alveolar macrophage is crucial to the defense of the lung from infection and may play a role in lung allograft rejection, we have begun to assess functions of this cell that are thought to be important in lung defense from infection and in transplant immunity. Antimicrobial functions include chemotaxis, which is a mechanism for recruiting macrophages to sites of inflammation and phagocytosis, and intracellular killing of microorganisms. As an accessory cell, the alveolar macrophage is necessary for an effective immune response to develop against either microorganisms or transplantation antigens. Our results indicate that the chemotactic, phagocytic but not the killing capability of alveolar macrophages from lung recipients is impaired. Alveolar macrophages and blood monocytes from lung recipients are also significantly impaired in their support for mitogen and antigen presentation to lymphocytes. Thus, the generation of an effective immune response to a microorganism may be impaired. Alveolar macrophages from lung recipients, however, function as well as those from normal subjects in stimulating lymphocyte proliferation in response to donor antigens (primed lymphocyte test) or unreleated allogeneic antigens (mixed lymphocyte reaction), while their respective blood monocytes function poorly in this regard. Our conclusions are that the antimicrobial functions of the alveolar macrophage are impaired after lung transplantation and this may be one mechanism to explain the unusual susceptibility of the lung allograft to infection. Those functions related to transplant immunity, however, are preserved and indicate that the alveolar macrophage may play a role in allograft rejection.     

Salicylate blockade of granulocyte adherence and the inflammatory response to experimental peritonitis.

Aspirin profoundly inhibited the in vitro augmentation of human and mouse granulocyte adherence to nylon fiber induced by the bacterial products Escherichia coli endotoxin and Staphylococcus aureus culture filtrate. Granulocytes obtained from normal volunteers during the 48 hr following ingestion of aspirin did not respond normally to endotoxin stimulation. Furthermore, pretreatment of mice with sodium salicylate prior to intraperitoneal infection with Streptococcus pneumoniae impaired granulocyte exudation and resulted in uncontrolled bacteremia and greater lethality of infection.     

Pulmonary macrophage antimicrobial activity in canine endotoxin shock and lung injury

Bacterial sepsis and pneumonia are common complications of lung injury and predispose the host to a poor resolution. We studied the functional integrity of pulmonary macrophages derived from minced lung preparations in a canine model of endotoxin-induced shock with acute lung injury. Dogs given 2 mg/kg of Escherichia coli endotoxin 055:B5 developed classic shock symptoms with concomitant acute lung injury; control animals given saline showed no physiological or pathological abnormalities. Compared to previous work with this canine model, the lung injury in this extended time period (6 h) had progressed to include alveolar edema. Six hours after endotoxin infusion, the left lung was lavaged, perfused, and the resulting lung minced for isolation of pulmonary macrophages. The endotoxic-model pulmonary macrophages showed several significant functional differences from controls. Although they elicited greater production of H2O2 (p less than 0.05), both phagocytosis of radiolabeled Staphylococcus aureus and E. coli (p less than 0.05) and bactericidal activity (p less than 0.05) were diminished compared to controls. Compared to alterations previously described in alveolar macrophages, these cells produced less H2O2 and demonstrated abnormal bacterial killing at all time points. These observations suggest that the functional alterations of pulmonary macrophages that follow acute lung injury contribute to the ineffective cell-mediated antimicrobial response. These derangements may promote an increased risk of nosocomial pneumonia, the high mortality often observed subsequent to pneumonia, or the propagation of acute lung injury that facilitates respiratory failure.     

The role of the macrophage in lung disease mediated by bacteria

Respiratory infections are a major cause of human morbidity and a leading cause of death. The lower respiratory tract is a sterile environment and host defense is well developed to clear bacteria. This response includes both humeral factors and resident and recruited cells. The alveolar macrophage is an integral component and its long-lifespan aids function. Following low-dose challenge alveolar macrophages clear bacteria from the lung, employing an over-lapping set of microbicidal strategies. At a higher-dose the phagocytic capacity of alveolar macrophages is overwhelmed but alveolar macrophages help orchestrate the inflammatory response. In the resolution phase of infection alveolar macrophages contribute to apoptosis induction and clearance of recruited cells. This process down-regulates pro-inflammatory cytokine production. Macrophage function is controlled by induction of apoptosis. Delayed-onset macrophage apoptosis contributes both to bacterial clearance and to resolution of the inflammatory response. Mcl-1, an anti-apoptotic protein with a very short half-life, is a key regulator of macrophage survival and therefore of host responses to common bacterial pathogens in the lung. Studies involving Streptococcus pneumoniae and other respiratory bacteria are discussed to illustrate these points and ephasise that the timing of macrophage apoptosis is important in determining its overall effect on the host pathogen interaction.     

Leukocytic response to inhaled bacteria.

Using histologic techniques, we have quantified the amount of infiltration of bronchi and alveoli by polymorphonuclear leukocytes during the 4 hours after an aerosol inoculation of mice with bacteria. Although the lungs of animals challenged with Staphylococcus aureus differed little from those of animals exposed only to a water aerosol, the lungs of animals exposed to Klebsiella pneumoniae or to Escherichia coli demonstrated significantly greater polymorphonuclear leukocyte infiltrations in bronchi and alveoli 2 and 4 hours afer exposure. These results suggest that the polymorphonuclear leukocyte may contribute to the early defense of the lung against some bacteria.     

痰液标本细菌培养及药敏试验对下呼吸道感染用药的指导作用

目的 分析痰液标本细菌培养及药敏试验结果分析对下呼吸道感染老年患者抗菌药物合理使用的影响.方法 选取我院2018年10月至2020年4月下呼吸道感染老年患者372例,均行痰液标本细菌培养及药敏试验,统计痰液标本细菌培养结果,分析主要病原菌构成,分析药敏试验结果,统计主要革兰阴性菌及主要革兰阳性菌耐药性.结果 372例患...     

Impaired bacterial degradation by monocytes and macrophages from a patient with treated Whipple's disease

A patient with Whipple's disease is described, and multiparameter flow cytometric examinations of several of the patient's phagocyte functions 3 and 9 mo after the start of oxytetracycline therapy are reported. Almost no intracellular degradation of Escherichia coli or Streptococcus pyogenes proteins and DNA occurred after ingestion by the patient's monocytes and macrophages. In addition, only minor digestion of phagocytized zymosan particles was detected. The mononuclear intracellular degradation was equally impaired 3 and 9 mo after the start of therapy. The monocyte and macrophage phagocytosis and intracellular killing, and all granulocyte phagocyte functions tested, were normal. The impaired mononuclear degradation of ingested material that was measured is consistent with the accumulation of periodic acid-Schiff-positive bacterial degradation products seen in macrophages of affected tissues in vivo, and suggests a key role of macrophage dysfunction in the pathogenesis of Whipple's disease.     

十堰地区婴幼儿社区获得性肺炎常见病原体致病情况及耐药性变迁分析

目的分析十堰地区婴幼儿社区获得性肺炎(CAP)常见病原体致病情况及耐药性的变迁。 方法选取2018年2月至2019年2月十堰区多家医院收治的1 282例CAP患儿,采集所有患儿深部痰液标本,对痰液中细菌菌种进行鉴定,采用MIC法进行药敏试验,并分析检出细菌对常用抗菌药物的耐药情况。 结果282例CAP患儿中病原体检出阳性者684例(53.35%),其中肺炎链球菌检出146例(21.35%),肺炎链球菌、大肠埃希菌、金黄色葡萄球菌、铜绿假单胞菌、产气肠杆菌、阴沟肠杆菌在年龄≤12个月的患儿中检出率明显高于年龄12～36个月的患儿(均P<0.05)。1 282例患儿肺炎支原体检出率为6.16%(79/1282),肺炎衣原体检出率为11.39%(146/1 282),肺炎支原体/衣原体在年龄12～36个月的患儿中检出率分别为13.71%(51/372)、25.81%(96/372)明显高于年龄≤12个月患儿的3.08%(28/910)、5.49%(50/910)(P<0.05)。在革兰氏阳性菌中,肺炎链球菌对红霉素、四环素、克林霉素耐药率均>80%,金黄色葡萄球菌对青霉素、红霉素、克林霉素、氨苄西林耐药率均>50%;肺炎链球菌和金黄色葡萄球菌对万古霉素、利奈唑胺均敏感。在革兰氏阴性菌中,大肠埃希菌和肺炎克雷伯菌均对头孢唑林、头孢他啶、头孢吡肟、头孢曲松、氨苄西林、氨曲南耐药率>70%;流感嗜血杆菌对氨苄西林耐药率最高;铜绿假单胞菌对头孢曲松、头孢替坦均100%耐药;革兰氏阳性菌对哌拉西林及阿米卡星耐药率最低。 结论十堰地区婴幼儿社区获得性肺炎常见病原体为肺炎链球菌,主要对红霉素、四环素、克林霉素耐药率均较高,临床应当使用敏感抗菌素提高治疗效率。     

Hydrogen peroxide production and killing of Staphylococcus aureus by human polymorphonuclear leukocytes.

The effects of bacterial neuraminidase on production of hydrogen peroxide (H2O2) and killing of Staphylococcus aureus by human polymorphonuclear leukocytes (PMN) were studied. The concentration of H2O2 was measured by the disappearance of scopoletin fluorescence in the presence of horseradish peroxidase. The results indicated that desialylation of human PMN inhibited the stimulation of H2O2 production during phagocytosis. It also markedly impaired the killing of S. aureus. Impaired killing of S. aureus by desialylated PMN was due to impaired intracellular killing rather than defective phagocytosis.     

Escherichia coli sacroiliitis: report of a case and review of the literature

Pyogenic sacroiliitis is rare and usually occurs in patients with an underlying illness. Typically, the responsible organisms are Staphylococcus aureus or Streptococcus pneumoniae. We describe a healthy 17-year-old boy with bacterial sacroiliitis caused by Escherichia coli. This case illustrates the importance of considering this diagnosis in febrile patients with no obvious source of infection.     

Pharmacodynamics of moxifloxacin and levofloxacin simulating human serum and lung concentrations

Fluoroquinolones are known to penetrate well into the infectious foci such as lung mucosa, epithelial lining fluid and alveolar macrophages achieving higher target site concentrations than the corresponding serum levels. In order to integrate the in vitro antibacterial activity and pharmacokinetics of moxifloxacin and levofloxacin, their bactericidal efficacy was assessed by simulating human serum and lung tissue concentrations using Streptococcus pneumoniae, Staphylococcus aureus and Klebsiella pneumoniae as indicator organisms. The bacteria were exposed to fluctuating moxifloxacin and levofloxacin concentrations simulating the drug levels in serum, lung mucosa, epithelial lining fluid and alveolar macrophages. The following parameters were deduced from the kill curves: area under the bactericidal kill curve normalized to the initial inoculum (AUBKC norm), the time needed to reduce the inoculum by 3 log(10) titers, and the initial bactericidal activity. In general, all these three parameters were for all the bacterial isolates having been exposed to moxifloxacin concentration dependent. In contrast, beyond a levofloxacin concentration of optimal bactericidal effect, higher drug concentrations did not further augment the bactericidal activity of levofloxacin. These data demonstrate that not all fluoroquinolones share the same pharmacodynamic targets needed to maximize their antibacterial effect.     

The pulmonary disposition of theophylline and its influence on human alveolar macrophage bactericidal function

We studied the pulmonary disposition of theophylline by performing bronchoalveolar lavage on 19 normal, nonsmoking volunteers who had taken theophylline orally for 14 days. In addition, we determined the influence of theophylline on human alveolar macrophage bacterial phagocytosis, intracellular killing, and hydrogen peroxide release. We found a 1:1 relationship between serum and bronchoalveolar lavage theophylline concentrations when lavage fluid concentrations were corrected for saline dilution. We found marked impairment of the bactericidal activity of alveolar macrophages from theophylline-treated subjects (intracellular killing efficiency of 24.7 +/- 1.5% compared with 60.2 +/- 0.9% by macrophages from control subjects; p less than 0.001). This defect in alveolar macrophage bactericidal activity was inversely correlated with the bronchoalveolar lavage theophylline concentrations, and was corrected after the alveolar macrophages were cultured under serum-free conditions for 48 h. Theophylline significantly impaired alveolar macrophage release of hydrogen peroxide. Hence, theophylline may compromise lung host defenses by suppressing alveolar macrophage bactericidal activity and oxidative metabolite release.     

社区及医院感染中常见细菌的耐药性分析

目的探讨社区和医院感染中细菌耐药谱的特点。方法药敏试验用KirbyBauer法,根据2003年美国临床实验室标准化委员会(NCCLS)标准判定结果,应用WHONET-5软件对临床分离细菌的药敏结果进行数据分析。结果医院感染480株,常见细菌依次为:铜绿假单胞菌(19.37%),肺炎克雷伯菌(15.83%),大肠埃希菌(11.87%)。社区感染726株,常见细菌为:金黄色葡萄球菌(14.05%),大肠埃希菌(12.67%),凝固酶阴性葡萄球菌(11.43%)。医院感染的金黄色葡萄球菌,凝固酶阴性葡萄球菌,铜绿假单胞菌,大肠埃希菌耐药率明显高于社区感染,差异有统计学意义(P<0.01)。而肺炎克雷伯菌和不动杆菌属差异无统计学意义。结论重视细菌耐药性监测,合理使用抗生素。     

河北省儿童医院1 927例儿童呼吸道感染病原谱流行病学分析

目的:分析河北省儿童医院儿童呼吸道感染病原谱的流行病学特点。方法:选取2018年1-12月河北省儿童医院呼吸道感染患儿1 927例进行回顾性研究,标本为鼻拭子、痰液或支气管肺泡灌洗液。采用恒温扩增技术完成靶基因的扩增和检测。对检测结果进行统计学分析。结果:肺炎支原体检出率为21.1%(406/1 927),肺炎链球菌检...