tetracycline and Respiratory-Distress-Syndrome

Topics: Acute Lung Injury; Animals; Anti-Bacterial Agents; Caspase 1; Enzyme Inhibitors; Humans; Immunomodulation; Inflammasomes; Interleukin-18; Interleukin-1beta; Mice; Models, Animal; Respiratory Distress Syndrome; Tetracycline

We describe the laboratory-confirmed etiologies of illness among participants in a hospital-based febrile illness cohort study in northern Tanzania who retrospectively met Integrated Management of Adolescent and Adult Illness District Clinician Manual (IMAI) criteria for septic shock, severe respiratory distress without shock, and severe pneumonia, and compare these etiologies against commonly used antimicrobials, including IMAI recommendations for emergency antibacterials (ceftriaxone or ampicillin plus gentamicin) and IMAI first-line recommendations for severe pneumonia (ceftriaxone and a macrolide). Among 423 participants hospitalized with febrile illness, there were 25 septic shock, 37 severe respiratory distress without shock, and 109 severe pneumonia cases. Ceftriaxone had the highest potential utility of all antimicrobials assessed, with responsive etiologies in 12 (48%) septic shock, 5 (14%) severe respiratory distress without shock, and 19 (17%) severe pneumonia illnesses. For each syndrome 17-27% of participants had etiologic diagnoses that would be non-responsive to ceftriaxone, but responsive to other available antimicrobial regimens including amphotericin for cryptococcosis and histoplasmosis; anti-tuberculosis therapy for bacteremic disseminated tuberculosis; or tetracycline therapy for rickettsioses and Q fever. We conclude that although empiric ceftriaxone is appropriate in our setting, etiologies not explicitly addressed in IMAI guidance for these syndromes, such as cryptococcosis, histoplasmosis, and tetracycline-responsive bacterial infections, were common.

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Ampicillin; Anti-Infective Agents; Bacterial Infections; Ceftriaxone; Child; Cohort Studies; Cryptococcosis; Emergencies; Female; Gentamicins; Histoplasmosis; Humans; Infections; Macrolides; Male; Microbial Sensitivity Tests; Middle Aged; Pneumonia, Bacterial; Respiratory Distress Syndrome; Shock, Septic; Tanzania; Tetracycline; Young Adult

A 65-year-old man was admitted because of high grade fever and cough after 3 days of gathering edible wild plants. Although ceftriaxone was given to him, his symptoms did not improve. His high grade fever escalated after changing the antibiotics (imipenem with erythromycin). His situation further declined with disseminated intravascular coagulation (DIC) and acute respiratory distress syndrome (ARDS). As a result, he was transferred to the Department of Respiratory Medicine 7 days after admission. He was intubated and placed on mechanical ventilation and treated by polymyxin-direct hemoperfusion. The eschar on his chest wall caused us to suspect Tsutsugamushi disease and a blood test confirmed our suspicion. Since the antibodies for Tsutsugamushi were elevated we arrived at the diagnosis of Tsutsugamushi disease with DIC and ARDS. The administration of tetracycline was sufficient to significantly improve his condition. Because its complications are life threatening, when we see a patient with fever and eruptions, it is necessary to keep in mind the possibility of Tsutsugamushi disease. Careful anamnesis and physical examinations are most important for the diagnosis of Tsutsugamushi disease.

Topics: Aged; Anti-Bacterial Agents; Antibodies, Bacterial; Biomarkers; Disseminated Intravascular Coagulation; Hemoperfusion; Humans; Male; Orientia tsutsugamushi; Polymyxins; Respiratory Distress Syndrome; Scrub Typhus; Serologic Tests; Severity of Illness Index; Tetracycline; Treatment Outcome

Sepsis causes more than with 215,000 deaths per year in the United States alone. Death can be caused by multiple system organ failure, with the lung, in the form of the acute respiratory distress syndrome (ARDS), often being the first organ to fail. We developed a chronic porcine model of septic shock and ARDS and hypothesized that blocking the proteases neutrophil elastase (NE) and matrix metalloproteinases (MMP-2 and MMP-9) with the modified tetracycline, COL-3, would significantly improve morbidity in this model. Pigs were anesthetized and instrumented for hemodynamic monitoring and were then randomized to one of three groups: control (n = 3), laparotomy only; superior mesenteric artery occlusion (SMA) + fecal blood clot (FC; n = 7), with intraperitoneal placement of a FC; and SMA + FC + COL (n = 5), ingestion of COL-3 12 h before injury. Animals emerged from anesthesia and were monitored and treated with fluids and antibiotics in an animal intensive care unit continuously for 48 h. Serum and bronchoalveolar lavage fluid (BALF) were sampled and bacterial cultures, MMP-2, MMP-9, NE, and multiple cytokine concentrations were measured. Pigs were reanesthetized and placed on a ventilator when significant lung impairment occurred (PaO2/FiO2 < 250). At necropsy, lung water and histology were assessed. All animals in the SMA + FC group developed septic shock evidenced by a significant fall in arterial blood pressure that was not responsive to fluids. Lung injury typical of ARDS (i.e., a fall in lung compliance and PaO2/FiO2 ratio and a significant increase in lung water) developed in this group. Additionally, there was a significant increase in plasma IL-1 and IL-6 and in BALF IL-6, IL-8, IL-10, NE, and protein concentration in the SMA + FC group. COL-3 treatment prevented septic shock and ARDS and significantly decreased cytokine levels in plasma and BALF. COL-3 treatment also significantly reduced NE activity (P < 0.05) and reduced MMP-2 and MMP-9 activity in BALF by 64% and 34%, respectively, compared with the SMA + FC group. We conclude that prophylactic COL-3 prevented the development of ARDS and unexpectedly also prevented septic shock in a chronic insidious onset animal model of sepsis-induced ARDS. The mechanism of this protection is unclear, as COL-3 inhibited numerous inflammatory mediators. Nevertheless, COL-3 significantly reduced the morbidity in a clinically applicable animal model, demonstrating the possibility that COL-3 may be useful in reduc

Topics: Animals; Bronchoalveolar Lavage Fluid; Cytokines; Disease Models, Animal; Female; Inflammation; Interleukin-1; Interleukin-10; Interleukin-6; Interleukin-8; Leukocyte Elastase; Lung; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Mesenteric Artery, Superior; Models, Chemical; Oxygen; Peptide Hydrolases; Pulmonary Edema; Respiratory Distress Syndrome; Sepsis; Swine; Tetracycline; Tetracyclines; Time Factors

Neutrophil activation with concomitant matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) release has been implicated in the development of sepsis-induced acute lung injury. We hypothesized that COL-3, a chemically modified tetracycline known to inhibit MMP-2 and MMP-9, would reduce lung injury and improve survival in rats following cecal ligation and puncture (CLP).. Sprague-Dawley rats were separated into five groups: 1) sham CLP+ carboxymethylcellulose (CMC; vehicle for COL-3, n = 6); 2) sham CLP + COL-3 (n = 6); 3) CLP + CMC (n = 10); 4) CLP + single-dose (SD) COL-3 administered concomitant with CLP (n = 9); and 5) CLP + multiple-dose (MD) COL-3 administered concomitant with CLP and at 24 h after CLP (n = 15). Rats were sacrificed at 168 h (7 days) or immediately after death, with survival defined as hours after CLP. Histological lung assessment was made based on neutrophil infiltration, alveolar wall thickening, and intraalveolar edema fluid. Lung MMP-2 and MMP-9 levels were assessed by immunohistochemistry. MMP-2 and MMP-9 levels were correlated with survival by simple regression analysis.. The mortality of rats in the cecal ligation and puncture without treatment group (CLP + CMC) was 70% at 168 h. A single dose of COL-3 in the CLP + COL-3 (SD) group significantly reduced mortality to 54%. Furthermore, with a repeat dose of COL-3 at 24 h after CLP, mortality was significantly reduced to 33%. Pathologic lung changes seen histologically in the CLP + CMC group were significantly reduced by COL-3. A significant reduction in lung tissue levels of MMP-2 and MMP-9 was noted in both groups treated with COL-3. Reduction of MMP-2 and MMP-9 levels correlated with improved survival.. Inhibition of MMP-2 and MMP-9 by COL-3 in a clinically relevant model of sepsis-induced acute lung injury reduces pulmonary injury and improves survival in a dose-dependent fashion. Our results suggest that prophylactic treatment with COL-3 in high-risk patients may reduce the morbidity and mortality associated with sepsis-induced acute respiratory distress syndrome.

Topics: Animals; Cecum; Chromatography, High Pressure Liquid; Disease Models, Animal; Enzyme Inhibitors; Ligation; Lung; Lung Diseases; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Matrix Metalloproteinase Inhibitors; Metalloendopeptidases; Punctures; Rats; Rats, Sprague-Dawley; Respiratory Distress Syndrome; Sepsis; Tetracycline; Tetracyclines

The acute respiratory distress syndrome (ARDS) occurs in patients with clearly identifiable risk factors, and its treatment remains merely supportive. We postulated that patients at risk for ARDS can be protected against lung injury by a prophylactic treatment strategy that targets neutrophil-derived proteases. We hypothesized that a chemically modified tetracycline 3 (COL-3), a potent inhibitor of neutrophil matrix metalloproteinases (MMPs) and neutrophil elastase (NE) with minimal toxicity, would prevent ARDS in our porcine endotoxin-induced ARDS model.. Yorkshire pigs were anesthetized, intubated, surgically instrumented for hemodynamic monitoring, and randomized into three groups: (1) control (n = 4), surgical instrumentation only; (2) lipopolysaccharide (LPS) (n = 4), infusion of Escherichia coli lipopolysaccharide at 100 microg/kg; and (3) COL-3 + LPS (n = 5), ingestion of COL-3 (100 mg/kg) 12 h before LPS infusion. All animals were monitored for 6 h following LPS or sham LPS infusion. Serial bronchoalveolar lavage (BAL) samples were analyzed for MMP concentration by gelatin zymography. Lung tissue was fixed for morphometric assessment at necropsy.. LPS infusion was marked by significant (P < 0.05) physiological deterioration as compared with the control group, including increased plateau airway pressure (P(plat)) (control = 15.7 +/- 0.4 mm Hg, LPS = 23.0 +/- 1.5 mm Hg) and a decrement in arterial oxygen partial pressure (P(a)O(2)) (LPS = 66 +/- 15 mm Hg, Control = 263 +/- 25 mm Hg) 6 h following LPS or sham LPS infusion, respectively. Pretreatment with COL-3 reduced the above pathophysiological changes 6 h following LPS infusion (P(plat) = 18.5 +/- 1.7 mm Hg, P(a)O(2) = 199 +/- 35 mm Hg; P = NS vs control). MMP-9 and MMP-2 concentration in BAL fluid was significantly increased between 2 and 4 h post-LPS infusion; COL-3 reduced the increase in MMP-9 and MMP-2 concentration at all time periods. Morphometrically LPS caused a significant sequestration of neutrophils and monocytes into pulmonary tissue. Pretreatment with COL-3 ameliorated this response. The wet/dry lung weight ratio was significantly greater (P < 0.05) in the LPS group (10.1 +/- 1.0 ratio) than in either the control (6.4 +/- 0.5 ratio) or LPS+COL-3 (7.4 +/- 0.6 ratio) group.. A single prophylactic treatment with COL-3 prevented lung injury in our model of endotoxin-induced ARDS. The proposed mechanism of COL-3 is a synergistic inhibition of the terminal neutrophil effectors MMPs and NE. Similar to the universal practice of prophylaxis against gastric stress ulceration and deep venous thromboses in trauma patients, chemically modified tetracyclines may likewise be administered to prevent acute lung injury in critically injured patients at risk of developing ARDS.

Topics: Animals; Antibiotics, Antineoplastic; Bronchoalveolar Lavage Fluid; Cardiac Output; Gelatin; Lipopolysaccharides; Metalloendopeptidases; Neutrophils; Pancreatic Elastase; Pulmonary Alveoli; Pulmonary Edema; Respiratory Distress Syndrome; Swine; Tetracycline; Tetracyclines

The authors report on a female patient of 26 years of age suffering from malaria tropica infection in her 36th week of pregnancy with fatal outcome. The newborn (after performance of Caesarean section) was infected connatally. Although infections with malaria are rare in Europe today--especially during pregnancy--there is a probability of rising incidence on account of increasing international tourism. Therapeutic problems are expected to multiply due to the resistance of Plasmodia to antiparasitary medication. Additionally pregnancy involves the risk of a more severe course of the disease in the mother. Pregnant women should be discouraged from travelling to countries with malarial risk because of the likelihood of a high rate of abortion, danger of intrauterine retardation, increased incidence of premature deliveries and risk of connatal infection of the newborn. If such warnings cannot be heeded, the persons concerned must be given all relevant information on conventional preventive measures in accordance with WHO recommendations and drug prophylaxis as recommended by a hospital or institution dealing with tropical diseases according to updated standards. The measures to be taken must be adapted to the individual risk of exposure of the patient.

Topics: Adult; Cesarean Section; Diagnosis, Differential; Female; Humans; Infant, Newborn; Malaria, Falciparum; Multiple Organ Failure; Oxygen; Pregnancy; Pregnancy Complications, Parasitic; Pregnancy Trimester, Third; Quinine; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Tetracycline

A dry cough, fever, generalized maculopapular rash, and myositis developed in a 67-year-old woman; she also had markedly abnormal liver function test results. Serologic tests proved that she had an infection of recent onset with Borrelia burgdorferi, the agent that causes Lyme disease. During a two-month course of illness, her condition remained refractory to treatment with antibiotics, salicylates, and steroids. Ultimately, fatal adult respiratory distress syndrome developed; this was believed to be secondary to Lyme disease.

Topics: Aged; Antibodies, Bacterial; Borrelia; Female; Humans; Immunoglobulin G; Immunoglobulin M; Lyme Disease; Penicillin G; Respiratory Distress Syndrome; Tetracycline