Comparison of ciprofloxacin and rifampicin in experimental Legionella pneumophila pneumonia

We evaluated intraperitoneal ciprofloxacin and rifampicin alone and as combination therapy in experimentally induced Legionella pneumophila pneumonia in guinea pigs. Intraperitoneal treatment began 48 h after intratracheal inoculation of 3 X 10(6) L. pneumophila and consisted of sterile saline (0.3 ml bid), ciprofloxacin (30 mg/kg bid), rifampicin (10 mg/kg/bid), or ciprofloxacin plus rifampicin (same doses). Animals were treated for five days and survivors killed after 11 days. Quantitative lung cultures were done post mortem. Respective mean and median days of animal survival were increased by treatment with ciprofloxacin plus rifampicin (8.4 and 9.5 days), ciprofloxacin (8.2 and 7.5 days), or rifampicin (8.3 and 7.5 days), compared with controls (5.5 and 5.0 days). Compared with control animals (log rank test) survival was improved by treatment with ciprofloxacin plus rifampicin (P less than or equal to 0.047) ciprofloxacin (P less than or equal to 0.047) or rifampicin (P less than or equal to 0.047). Quantitative lung cultures (cfu/g) were also decreased by treatment with ciprofloxacin plus rifampicin (2.0 X 10(4)), ciprofloxacin (5.4 X 10(4)), or rifampicin (1.7 X 10(4)) compared with controls (3.2 X 10(8)). No differences in survival, quantitative lung cultures, or animal weights were noted between treatment groups. This study demonstrates that ciprofloxacin is as effective as rifampicin in the treatment of experimentally induced L. pneumophila pneumonia and that the combination of ciprofloxacin plus rifampicin has no advantages over single agent therapy in this model.     

Airways delivery of rifampicin microparticles for the treatment of tuberculosis

A Mycobacterium tuberculosis (H37Rv)-infected guinea pig model was used to screen for targeted delivery to the lungs by insufflation (with lactose excipient) or nebulization, of either rifampicin alone, rifampicin within poly(lactide-co-glycolide) microspheres (R-PLGA) or polymer microparticles alone (PLGA). Animals treated with single and double doses of R-PLGA microspheres exhibited significantly reduced numbers of viable bacteria, inflammation and lung damage compared with lactose-, PLGA- or rifampicin-treated animals 28 days post-infection (P < 0.05). Two doses of R-PLGA resulted in reduced splenic enlargement. These studies support the potential of R-PLGA delivered to the lung to treat pulmonary tuberculosis.     

Methadone during pregnancy in the rat: dose level effects on maternal and perinatal mortality and growth in the offspring.

Four groups of pregnant rats were administered methadone hydrochloride orally on days 8 through 22 of gestation. Each group initially received 5 mg/kg for 4 days. One group was maintained at this level and the remaining groups were increased to maintenance doses of 10, 15 or 20 mg/kg increments at 4-day intervals. An intubation control group received the vehicle only. Nontreated control mothers were left undisturbed. All offspring were fostered to other nontreated mothers at birth. Methadone, particularly at the higher dose levels, reduced maternal weight gain during pregnancy and increased both maternal mortality and total mortality among the young (resorptions plus stillbirths). Birth weight covaried with dose level and litter size: the 5, 10 and 15 mg/kg doses yielded litter sizes comparable, to, or somewhat smaller than, controls, but with lower birth weights; the 20 mg/kg doses yielded the smallest litter sizes but with birth weights greater than any other treated or control group. Beyond day 1 of life, treated and control offspring did not differ in mortality. By weaning, the low offspring weights seen at birth had been compensated for and were no longer evident. Body weights of offspring of mothers in the 20 mg/kg group remained well above average through weaning. In a second experiment, blood levels of methadone were determined for both mothers and litters in the 5, 10 and 15 mg/kg groups, sacrificed 24 hours before expected parturition. Blood levels were dose-related and corresponded to those found in human subjects receiving daily maintenance doses of approximately 30, 60 and 100 mg, respectively.     

Chemotherapeutic potential of alginate-chitosan microspheres as anti-tubercular drug carriers

OBJECTIVES: This study was designed to develop alginate-chitosan microspheres as drug carriers to reduce dose/dosing frequency in the management of tuberculosis (TB), which otherwise demands prolonged chemotherapy. METHODS: Alginate-chitosan microspheres encapsulating three frontline anti-tuberculous drugs (ATDs), rifampicin, isoniazid and pyrazinamide, were formulated. A therapeutic dose and a half-therapeutic dose of the microsphere-encapsulated ATDs were orally administered to guinea pigs for pharmacokinetic/chemotherapeutic evaluations, respectively. RESULTS: The drug encapsulation efficiency ranged from 65% to 85% with a loading of 220-280 mg of drug per gram microspheres. Administration of a single oral dose of the microspheres to guinea pigs resulted in sustained drug levels in the plasma for 7 days and in the organs for 9 days. The half-life and mean residence time of the drugs were increased 13- to 15-fold by microsphere encapsulation, along with an enhanced relative/absolute bioavailability. The sustained release and increase in bioavailability were also observed with a sub-therapeutic dose of the microspheres. In Mycobacterium tuberculosis H37Rv-infected guinea pigs, administration of a therapeutic dose of microspheres spaced 10 days apart produced a clearance of bacilli equivalent to conventional treatment for 6 weeks. The most important observation, however, was the documentation of therapeutic benefit with a half-therapeutic dose of the microspheres administered weekly. CONCLUSION: Alginate-chitosan microspheres hold promise as a potential natural polymer-based oral ATD carrier for better management of TB.     

Inhaled large porous particles of capreomycin for treatment of tuberculosis in a guinea pig model

Capreomycin is used for the treatment of multidrug-resistant tuberculosis (MDR-TB), but it is limited therapeutically by its severe side effects. The objectives of the present studies were (i) to design low-density porous capreomycin sulfate particles for efficient pulmonary delivery to improve local and systemic drug bioavailability and capacity to reduce the bacillary load in the lungs in a manner similar to that achieved with intramuscular injections; (ii) to determine pharmacokinetic parameters after pulmonary administration of these capreomycin particles; and (iii) to evaluate the efficacy of these particles in treating animals in a small-aerosol-inoculum guinea pig model of TB. Capreomycin particles were manufactured by spray drying and characterized in terms of size and drug content. Pharmacokinetic parameters were determined by noncompartmental methods with healthy guinea pigs after administration of capreomycin particles by insufflation. The efficacy of the particles was evaluated by histopathological analysis and in terms of wet organ weight and bacterial burden in TB-infected animals. Lungs of animals receiving a 14.5-mg/kg dose of capreomycin particles showed significantly lower wet weights and smaller bacterial burdens than those of animals receiving any other treatment. These results were supported by histopathological analysis. The feasibility of inhaling capreomycin in a novel powder form, with the ultimate objective of the treatment of MDR-TB, is demonstrated by pharmacokinetic and pharmacodynamic studies with guinea pigs. If applied to humans with MDR-TB, such a therapeutic approach might simplify drug delivery by eliminating injections and might reduce adverse effects through lowering the dose.     

Pharmacokinetics of sequential doses of capreomycin powder for inhalation in guinea pigs

The global control of tuberculosis (TB) is at risk by the spread of multidrug-resistant TB (MDR TB). Treatment of MDR TB is lengthy and involves injected drugs, such as capreomycin, that have severe side effects. It was previously reported that a single daily dose of inhaled capreomycin had a positive effect on the bacterial burden of TB-infected guinea pigs. The modest effect observed was possibly due to a dose that resulted in insufficient time of exposure to therapeutic systemic and local levels of the drug. In order to determine the length of time that systemic and local drug concentrations are above therapeutic levels during the treatment period, the present study investigated the disposition of capreomycin powders after sequential pulmonary administration of doses of 20 mg/kg of body weight. Capreomycin concentrations in bronchoalveolar lavage fluid and lung tissue of animals receiving a series of one, two, or three doses of capreomycin inhalable powder were significantly higher (50- to 100-fold) at all time points than plasma concentrations at the same time points or those observed in animals receiving capreomycin solution by intramuscular (i.m.) injection (10- to 100-fold higher). Notably, at the end of each dosing period, capreomycin concentrations in the lungs were approximately 100-fold higher than those in plasma and severalfold higher than the MIC, suggesting that sufficient capreomycin remains in the lung environment to kill Mycobacterium tuberculosis. No accumulation of capreomycin powder was detected in the lungs after 3 pulmonary doses. These results indicate that the systemic disposition of capreomycin after inhalation is the same as when injected i.m. with the advantage that higher drug concentrations are present at all times in the lungs, the primary site of infection.     

Subinhibitory antibiotics reduce Pseudomonas aeruginosa tissue injury in the rat lung model

Using the agar-bead rat lung model, we evaluated the effects of subinhibitory antibiotic treatment upon Pseudomonas aeruginosa exoenzyme expression and lung injury in vivo. One hundred and twenty-eight animals were separated into two groups of 64 animals. One group was inoculated with P. aeruginosa DG1, and the other with P. aeruginosa 3740. Each of these two groups was divided into four subgroups of 16 animals on the basis of ten-day antibiotic treatment with ciprofloxacin, tobramycin and ceftazidime or untreated controls. P. aeruginosa DG1 is non-mucoid and expresses significant yields of exoenzyme S and elastase. P. aeruginosa 3740 is a mucoid organism isolated from the sputum of a cystic fibrosis patient, and demonstrates modest elastase activity only (10% of DG1 levels). Lung bacterial counts were similar in treatment and control groups. Lungs from antibiotic-treated rats demonstrated fewer histological changes than those from untreated animals (P less than 0.001). DG1 lung isolates from antibiotic-treated animals yielded less elastase and exoenzyme S compared with isolates from untreated animals (P less than 0.001). No detectable decrease in elastase or mucoid phenotype was observed in 3740 lung isolates from antibiotic treated animals. Thus, antibiotic protection against lung injury by P. aeruginosa may involve modulation of virulence factors.     

Administration of efavirenz (600 mg/day) with rifampicin results in highly variable levels but excellent clinical outcomes in patients treated for tuberculosis and HIV

OBJECTIVES: Pharmacokinetic interactions between rifampicin and antiretroviral therapy (ART), including efavirenz, are problematic and need to be better defined to determine proper dose and to be correlated with short-term and long-term clinical outcomes. PATIENTS AND METHODS: Consenting patients with smear-positive pulmonary TB and HIV received once daily didanosine + lamivudine + efavirenz (600 mg), with rifampicin-containing TB regimen by directly observed therapy and self-administration at TB therapy completion. Trough efavirenz levels were measured by HPLC at 1, 2, 4 and 6 months while on rifampicin and after discontinuation. HIV and TB outcomes were monitored. RESULTS: Twenty African patients were enrolled [15 female, mean age 31 years, baseline weight 59.4 kg (range 45-97), viral load 5.75 log10 copies/mL and CD4 230 cells/mm3]. Seventy-two efavirenz concentrations were available from 19 patients (58 on, 14 after rifampicin). The geometric mean efavirenz concentration was 1730 ng/mL (range 354-27,179) on and 1377 ng/mL (range 572-3975) off rifampicin (P = 0.55). Inter-subject variability in efavirenz concentrations was greater on rifampicin (CV 157% versus 58% off) with relatively consistent intra-subject variation over time (median CV 24%). Over half of patients had efavirenz concentrations above or below the expected therapeutic range (1000-4000 ng/mL). Efavirenz levels were not predicted by weight or gender and were not associated with HIV clinical outcomes. Overall 80% of patients had non-detectable viral loads at 6 months and 65% at 21 months with a cumulative CD4 cell increase of 196 cells/mm3. CONCLUSIONS: In this longitudinal study, despite wide variability in plasma efavirenz concentrations during rifampicin administration, excellent clinical outcomes were obtained. In African patients treated for HIV and TB, our data support the routine use of efavirenz at 600 mg/day when receiving rifampicin.     

Antifungal activity and pharmacokinetics of posaconazole (SCH 56592) in treatment and prevention of experimental invasive pulmonary aspergillosis: correlation with galactomannan antigenemia

The antifungal efficacy, safety, and pharmacokinetics of posaconazole (SCH 56592) (POC) were investigated in treatment and prophylaxis of primary pulmonary aspergillosis due to Aspergillus fumigatus in persistently neutropenic rabbits. Antifungal therapy consisted of POC at 2, 6, and 20 mg/kg of body weight per os; itraconazole (ITC) at 2, 6, and 20 mg/kg per os; or amphotericin B (AMB) at 1 mg/kg intravenously. Rabbits treated with POC showed a significant improvement in survival and significant reductions in pulmonary infarct scores, total lung weights, numbers of pulmonary CFU per gram, numbers of computerized-tomography-monitored pulmonary lesions, and levels of galactomannan antigenemia. AMB and POC had comparable therapeutic efficacies by all parameters. By comparison, animals treated with ITC had no significant changes in outcome variables in comparison to those of untreated controls (UC). Rabbits receiving prophylactic POC at all dosages showed a significant reduction in infarct scores, total lung weights, and organism clearance from lung tissue in comparison to results for UC (P < 0.01). There was dosage-dependent microbiological clearance of A. fumigatus from lung tissue in response to POC. Serum creatinine levels were greater (P < 0.01) in AMB-treated animals than in UC and POC- or ITC-treated rabbits. There was no elevation of serum hepatic transaminase levels in POC- or ITC-treated rabbits. The pharmacokinetics of POC and ITC in plasma demonstrated dose dependency after multiple dosing. The 2-, 6-, and 20-mg/kg dosages of POC maintained plasma drug levels above the MICs for the entire 24-h dosing interval. In summary, POC at > or =6 mg/kg/day per os generated sustained concentrations in plasma of > or =1 microg/ml that were as effective in the treatment and prevention of invasive pulmonary aspergillosis as AMB at 1 mg/kg/day and more effective than cyclodextrin ITC at > or =6 mg/kg/day per os in persistently neutropenic rabbits.     

Two cases of tuberculous retropharyngeal abscess in adults

Retropharyngeal abscess (RPA) is an acute or chronic deep neck tissue infection. Tuberculous RPA is chronic and extremely rare in adults. A 20-year-old female patient visited the local hospital due to cough and sputum. The sputum smear was positive for acid-fast staining, and lung computed tomography (CT) indicated pulmonary tuberculosis (TB). The patient received the standard regimen of isoniazid+rifampicin+pyrazinamide+ethambutol (HRZE) for 6 months. After HRZE, pulmonary symptoms improved, but some pharyngeal discomfort remained. In another case, a 25-year-old male patient was admitted to our hospital because of a mass on the left side of his neck. Lymph node TB was considered after a puncture biopsy. Lung CT showed no obvious abnormality. After HRZE for 5 months, the mass had progressively enlarged. Both patients underwent B-ultrasonography-guided puncture, and Xpert® MTB/RIF of the abscess was positive and rifampin-sensitive. Tuberculous RPA was diagnosed and treated with isoniazid+rifampicin (HR) for 12 months. After combination anti-TB therapy and surgical drainage, both patients fully recovered. Tuberculous RPA is rare in adults; because of pharyngeal symptoms or progressive enlargement of a neck mass with anti-TB treatment, clinicians need to suspect tuberculous RPA in adults, which is treated with anti-TB therapy and surgery.     

Teicoplanin and rifampicin singly and in combination in the treatment of experimental Staphylococcus epidermidis endocarditis in the rabbit model

Teicoplanin and rifampicin were evaluated as single and combined agents in the treatment of endocarditis due to Staphylococcus epidermidis in the rabbit model. Rabbits were treated for ten days and the number of bacteria in vegetations determined. At the end of ten days the geometric mean number of bacteria in the vegetations were 5.53 X 10(8), 6.68 X 10(6). 1.10 X 10(4), 2.57 X 10(1) cfu/g of vegetation for control, teicoplanin, rifampicin, and teicoplanin plus rifampicin groups respectively. The MIC and MBC values of the S. epidermidis isolates were 0.78 mg/l for teicoplanin and less than or equal to 0.10 mg/l for rifampicin. In the rifampicin treated group three post-treatment isolates of S. epidermidis tested exhibited marked resistance to rifampicin with MIC and MBC values greater than or equal to 200 mg/l. Teicoplanin and rifampicin were both effective as single agents in the clearance of S. epidermidis from the bloodstream. Rifampicin was more effective than teicoplanin in the clearance of S. epidermidis from vegetations but teicoplanin in combination with rifampicin was more effective than either drug alone.     

氨溴索对大鼠的利福平药动学影响

目的研究氨溴索对大鼠体内利福平药代动力学的影响,评价药物间的相互作用及联合用药的合理性。方法采用1个剂量组,2种用药方案分别单次给药。利福平给药量为30 mg/kg,合并用药时,先尾静脉注射氨溴索15 mg/kg,20min后再尾静脉注射利福平。给药后于10 min、30 min、1、2、4、6、8、10、14、20 h采集血样,用反相HPLC-UV检测法测定血药浓度。据利福平在体内经时过程,用BAPP 2.0统计软件求算该药单用及联合用药后的药动学参数。结果利福平单用组主要药动学参数:Ke为0.09/h,t1/2为7.35 h,AUC0→20为391.65 h/(μg.mL),AUC0→∞为447.93 h/(μg.mL);合用组:Ke为0.09/h,t1/2为7.43 h,AUC0→20为368.65 h/(μg.mL),AUC0→∞为424.10 h/(μg.mL)。两者参数无显著性差异。结论氨溴索与利福平在联合使用时对大鼠利福平药代动力学无明显影响,临床上二者联合使用安全,为临床安全有效地使用氨溴索和利福平提供实验依据。     

Subinhibitory concentrations of tetracycline inhibit surface expression of the Pseudomonas aeruginosa ferripyochelin binding protein in vivo

The effects of subinhibitory concentrations of tetracycline on surface expression of Pseudomonas aeruginosa ferripyochelin binding protein (FBP) and P. aeruginosa virulence in a pulmonary infection model in rats were examined. Rats were inoculated intratracheally with P. aeruginosa strain DG1 embedded in agar beads. One half of the inoculated animals served as untreated controls while the other half received daily injections of 15 mg/kg tetracycline. FBP was shown to be surface exposed in bacteria isolated from control animals using indirect immunofluorescence and immunoelectron microscopy. No FBP was detectable, however, on the surface of bacteria isolated from the lungs of animals treated with tetracycline. The numbers of bacteria recovered from the lungs of infected animals did not differ between control and tetracycline treated groups, although the degree of pathology observed in tetracycline treated animals was significantly lower than in untreated controls (P = 0.002, one way ANOVA). Sub-inhibitory doses of tetracycline reduced proteolytic activity in vitro, but had no effect on the activities of exotoxin A or exoenzyme S. These studies suggest that exposure to subinhibitory concentrations of tetracycline can repress FBP surface expression as well as proteolytic activity in P. aeruginosa leading to a significant decrease in lung injury during infections due to this organism.     

Inability of niacin to protect from in vivo hyperoxia or in vitro microsomal lipid peroxidation

Abstract

The efficacy of niacin in protecting rats from normobaric hyperoxia was evaluated in vivo by exposing niacin treated animals and controls to ≥ 95% O₂ for 96 hours. The vitamin was also evaluated as a possible free radical scavenger in vitro using an Fe-ascorbate initiated microsomal lipid peroxidation system. No protective effects were observed in vivo either in mortality or in differences in lung wet and dry weights of the niacin treated rats when compared to controls. Niacin in varying concentrations also did not decrease lipid peroxidation in the microsomal systems. Although this vitamin has been reported to protect animals from paraquat toxicity when given intraperitoneally once daily, niacin administered in similar doses does not appear to protect rats from hyperoxia.     

Comparative evaluation of tigecycline and vancomycin, with and without rifampicin, in the treatment of methicillin-resistant Staphylococcus aureus experimental osteomyelitis in a rabbit model

OBJECTIVES: Staphylococcus aureus is the most common organism isolated in osteomyelitis. Methicillin-resistant S. aureus (MRSA) infections are particularly difficult to treat. We evaluated the efficacy of tigecycline and vancomycin with and without rifampicin in a rabbit model of MRSA osteomyelitis. METHODS: A 28 day antibiotic therapy with a subcutaneous injection of tigecycline (14 mg/kg twice daily), with and without oral rifampicin (40 mg/kg twice daily); or subcutaneous administration of vancomycin (30 mg/kg twice daily), with and without oral rifampicin (40 mg/kg twice daily) were compared. Osteomyelitis was induced with an intramedullary injection of 10(6) colony-forming units of MRSA. Infected rabbits were randomly divided into six groups: tigecycline, tigecycline with oral rifampicin, vancomycin, vancomycin with oral rifampicin, and no treatment control and tigecycline bone penetration groups. Treatment began 2 weeks after infection. After 4 weeks of therapy, the rabbits were left untreated for 2 weeks. Rabbits were then euthanized, and the tibias were harvested. The bones were cultured, and bacterial counts of MRSA were performed. RESULTS: Rabbits that received tigecycline and oral rifampicin therapy (n=14) showed a 100% infection clearance. Rabbits treated with tigecycline (n=10) showed a 90% clearance. Rabbits treated with vancomycin and oral rifampicin (n=10) also showed a 90% clearance. Rabbits treated with vancomycin (n=11) showed an 81.8% clearance. Untreated controls (n=15) demonstrated only a 26% clearance. For the tigecycline bone penetration group, the bone concentrations of tigecycline in the infected tibia were significantly higher than the non-infected ones. CONCLUSIONS: Tigecycline may be an effective alternative to vancomycin in the treatment of MRSA osteomyelitis.     

Propranolol ameliorates the development of portal-systemic shunting in a chronic murine schistosomiasis model of portal hypertension.

We investigated the role of early portal hypotensive pharmacotherapy in preventing the development of portal-systemic shunting in a portal hypertensive model of chronic murine schistosomiasis induced by infecting C3H mice with 60 cercariae of Schistosoma mansoni. Propranolol was administered in drinking water to 20 animals for a period of 6 wk at a dose of 10 mg.kg-1d-1, starting at 5 wk of schistosomal infection. 32 age-matched mice with chronic schistosomal infection served as controls. All animals were studied 11 wk after the infection. Compared with controls the portal pressure (10.8 +/- 0.40 mmHg) was significantly lower (P less than 0.001) in the propranolol-treated animals (7.9 +/- 0.80 mmHg). Portal-systemic shunting was decreased by 79%, from 12.2 +/- 3.34% in controls to 2.5 +/- 0.99% in the propranolol group (P less than 0.05). Portal venous inflow was reduced by 38% in the propranolol treated animals (2.50 +/- 0.73 ml/min; n = 6) compared with controls (4.00 +/- 0.34 ml/min; n = 8; P less than 0.05). The worm burden, the granulomatous reaction, the collagen content of the liver, and the serum bile acid levels were not significantly different between the two groups of animals. These results demonstrate that in chronic liver disease induced by schistosomiasis, the development of portal-systemic shunting can be decreased or prevented by the reduction of flow and pressure in the portal system.     

2017年浙江省宁波市肺结核患者耐药特征分析

目的初步了解浙江省宁波市初治涂阴肺结核患者耐药情况,为完善耐药肺结核控制策略提供参考信息。方法对2017年3 — 12月宁波市各级结核病定点医院登记的1 434例初治涂阴肺结核患者的痰标本进行分离培养,采用 世界卫生组织/国际防痨和肺病联合会 推荐的比例法对培养阳性菌株开展菌种鉴定和药物敏感性检测。结果1 434例初治涂阴肺结核患者中378例培养阳性,其中60例鉴定为非结核分枝杆菌感染,318例结核分枝杆菌感染者中86例为耐药患者,总耐药率为27.04%,异烟肼耐药率最高,为17.92%（57/86）;利福平耐药率最低,为5.35%（17/86）。 有空洞肺结核患者利福平耐药率高于无空洞患者（χ2＝5.319,P＜0.05）。结论宁波市初治涂阴肺结核疫情较为严峻,需进一步扩大筛查范围,及时发现和诊断耐药肺结核患者,提高患者治疗和管理水平。     

Precordial compression without airway management induces lung injury in the rodent cardiac arrest model with central apnea.

To investigate whether the lung injury induced by precordial compression without ventilation or not, in the cardiac-arrest animal model with central apnea. Thirty male Sprague-Dawley rats were anesthetized with halothane. The cardiac arrest was induced by 100 mg/kg ketamine (IV) and accompanied with central apnea. They were allocated to four groups by means of resuscitation. Group A was treated with only precordial compression without the other treatments. In group B with tracheotomy and precordial compression. In group C was performed tracheotomy, oxygenation, and precordial compression. The animals in group D were treated with tracheotomy, oxygen administration, artificial ventilation, and precordial compression. Four minutes after cardiac arrest, the resuscitation was started and continued for 20 min. PaCO(2) in the group without mechanical ventilation increased significantly after the start of the resuscitation. All animals were sacrificed after resuscitation procedure. The wet/dry weight ratio of lung in group A (6.9+/-0.8) was significantly higher than that of the other groups B, C and D (5.9+/-0.6, 5.7+/-0.4 and 5.6+/-0.4, P<0.05 in each). The pathological findings also demonstrated the lung injuries, such as edema, migration, and destruction of structure in group A. The precordial compression alone did not improve CO(2) elimination in the gasping-less cardiac arrest model, as well as maybe inducing more severe lung injury than that with the protective management. This experimental model raises the possibility that chest compressions without airway management might result in lung injury.     

Effects of two antibiotic regimens on course and persistence of experimental Chlamydia pneumoniae TWAR pneumonitis.

We studied the effects of two antibiotic regimens on the course of Chlamydia pneumoniae infection in the lungs of Swiss Webster mice. After intranasal challenge with isolates AR-388 (1.3 x 10(7) inclusion-forming units per mouse) and AR-39 (1.5 x 10(6) inclusion-forming units per mouse), groups of animals were treated with either doxycycline (10 mg/kg of body weight once a day for 3 days), azithromycin (10 mg/kg [single dose]), or saline. Responses were assessed by the isolation of organisms in cell culture, detection of TWAR DNA in lung tissues by PCR, and lung histology. Both regimens were effective in clearing infections induced by AR-388 (P = 0.02 and 0.007 for doxycycline and azithromycin, respectively) compared with controls. TWAR DNA was detected in 77 and 25% of culture-negative lungs 2 weeks after treatment of AR-388 and AR-39 infections, respectively. Histological changes showed interstitial pneumonitis and were similar over time for all groups. Single-dose azithromycin produced drug levels in lung tissues above the MICs for the test strains for a period three times longer than that of single-dose doxycycline. We concluded that short-term antibiotic regimens were successful for the treatment of experimental TWAR pneumonitis in mice. TWAR DNA was frequently recovered from lung tissues after apparently successful treatment.     

Increasing inspiratory time exacerbates ventilator-induced lung injury during high-pressure/high-volume mechanical ventilation

INTRODUCTION: Ventilator-induced lung injury may be caused by overdistension of alveoli during high-pressure ventilation. In this study, we examined the effects of increasing inspiratory time on ventilator-induced lung injury. METHODS: Sprague-Dawley rats were divided into four different groups with ten animals per group. Each group was then ventilated for 30 mins with one of four ventilator strategies. All groups were ventilated with an Fio2 of 1.0 and a positive end-expiratory pressure of 0 cm H2O. Group LoP was the negative control group and was ventilated with low pressures (peak inspiratory pressure = 12 cm H2O, rate = 30, and inspiratory time = 0.5 secs). Groups iT = 0.5, iT = 1.0, and iT = 1.5 were the experimental groups and were ventilated with high pressures (peak inspiratory pressure = 45 cm H2O, rate = 10, and inspiratory times = 0.5 secs, iT = 1.0 sec, and iT = 1.5 secs, respectively). Outcome measures included lung compliance, Pao /Fio ratio, wet/dry lung weight, and dry lung/body weight. RESULTS: Final static lung compliance (p =.0002) and Pao2/Fio2 (p =.001) decreased as inspiratory time increased. Wet/dry lung weights (p <.0001) and dry lung/body weights (p <.0001) increased as inspiratory time increased. Light microscopy revealed evidence of intra-alveolar edema and hemorrhage in the iT = 1.0 and iT = 1.5 animals but not the LoP and iT = 0.5 animals. CONCLUSION: Increasing inspiratory time during high-pressure/high-volume mechanical ventilation is associated with an increase in variables of lung injury.