minocycline and Multiple-Organ-Failure

This large prospective non-interventional study investigated the effects of tigecycline either as single agent or in combination with other antimicrobial agents in 1,025 patients treated in clinical routine at German hospitals. Sixty-five percent of the patients had APACHE II scores > 15, indicating high overall disease severity. Complicated intra-abdominal infections (cIAI) or complicated skin and skin tissue infections (cSSTI) were the most common indications, with Staphylococcus aureus, Enterococcus faecium and Escherichia coli being the most frequently isolated pathogens. Clinical success was reported at the end of tigecycline therapy in 74.2% of the total population, in 75.4% of the cIAI and in 82.2% of the cSSTI patients. The subpopulation (28.0% of the patients) infected with multidrug-resistant pathogens (methicillin-resistant S. aureus, extended-spectrum β-lactamase producers and vancomycin-resistant enterococci) were treated with similar success rates as the overall population. Tigecycline was generally well tolerated. Drug-related adverse events (AEs) were reported in 7.7% of the total population; 2.5% had serious AEs mostly attributable to inefficacy of therapy or deterioration of the disease. Mortality rates were consistent with the types of infection and severity of illness. There was no indication of excessive mortality associated with tigecycline as had been suggested in previously performed meta-analyses. In this large non-interventional study performed in the clinical routine setting, tigecycline achieved favorable clinical success rates in a patient population with high severity of illness and a high prevalence of multidrug-resistant pathogens and showed a good safety and tolerability profile.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; APACHE; Drug Therapy, Combination; Enterococcus; Escherichia coli; Female; Germany; Humans; Intensive Care Units; Intraabdominal Infections; Logistic Models; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Minocycline; Multiple Organ Failure; Prospective Studies; Sepsis; Severity of Illness Index; Skin Diseases, Bacterial; Staphylococcus aureus; Tigecycline; Treatment Outcome; Young Adult

Tigecycline is a broad spectrum antimicrobial agent, structurally similar to minocycline and that shares some tetracycline-related side effects. A case report is presented on a 68-year-old female who received tigecycline for a sepsis of unknown origin and who, in the following 5days, developed abdominal pain and elevated pancreatic enzymes, which suggested acute pancreatitis. After ruling out other origins, and according to the Naranjo adverse drug reaction probability scale, tigecycline was the probable cause of the acute pancreatitis, a complication that has been reported 5 times in the database of the Spanish pharmacosurveillance system since 2009. Close monitoring of abdominal signs and symptoms is recommended during treatment with tigecycline, since adverse effects affecting the digestive system are the most prevalent ones when using this drug.

Topics: Acute Disease; Aged; Anti-Bacterial Agents; Critical Care; Drug Substitution; Fatal Outcome; Female; Humans; Minocycline; Multiple Organ Failure; Pancreatitis; Sepsis; Tigecycline

Despite recovery of hemodynamics by fluid resuscitation after hemorrhage, development of the systemic inflammatory response and multiple organ dysfunction syndromes can nonetheless lead to death. Minocycline and doxycycline are tetracycline derivatives that are protective in models of hypoxic, ischemic, and oxidative stress. Our aim was to determine whether minocycline and doxycycline protect liver and kidney and improve survival in a mouse model of hemorrhagic shock and resuscitation.. Mice were hemorrhaged to 30 mmHg for 3 h and then resuscitated with shed blood followed by half the shed volume of lactated Ringer's solution containing tetracycline (10 mg/kg), minocycline (10 mg/kg), doxycycline (5 mg/kg), or vehicle. For pretreatment plus posttreatment, drugs were administered intraperitoneally prior to hemorrhage followed by second equal dose in Ringer's solution after blood resuscitation. Blood and tissue were harvested after 6 h.. Serum alanine aminotransferase (ALT) increased to 1,988 and 1,878 U/L after posttreatment with vehicle and tetracycline, respectively, whereas minocycline and doxycycline posttreatment decreased ALT to 857 and 863 U/L. Pretreatment plus posttreatment with minocycline and doxycycline also decreased ALT to 849 and 834 U/L. After vehicle, blood creatinine increased to 134 µM, which minocycline and doxycycline posttreatment decreased to 59 and 56 µM. Minocycline and doxycycline pretreatment plus posttreatment decreased creatinine similarly. Minocycline and doxycycline also decreased necrosis and apoptosis in liver and apoptosis in both liver and kidney, the latter assessed by TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling) and caspase 3 activation. Lastly after 4.5 h of hemorrhage followed by resuscitation, minocycline and doxycycline (but not tetracycline) posttreatment improved 1-week survival from 38% (vehicle) to 69% and 67%, respectively.. Minocycline and doxycycline were similarly protective when given before as after blood resuscitation and might therefore have clinical efficacy to mitigate liver and kidney injury after resuscitated hemorrhage.

Topics: Alanine Transaminase; Animals; Apoptosis; Biomarkers; Caspase 3; Creatinine; Cytoprotection; Disease Models, Animal; Doxycycline; Fluid Therapy; Hemodynamics; Kidney; Liver; Male; Mice, Inbred C57BL; Minocycline; Multiple Organ Failure; Necrosis; Protective Agents; Resuscitation; Shock, Hemorrhagic; Tetracycline; Time Factors

A 77-year-old woman who have no past history, was admitted in a local hospital in Muroto City, Kochi, Japan, after several days of fever and severe general fatigue and generalized skin erythema. She was suspected to have Japanease spotted fever, which was a local pandemic disease. She was treated with minocycline immediately. The next day, she had consciousness disturbance and low blood pressure. Laboratory findings indicated disseminated intravascular coagulation (DIC) and multiple organ failure. She was referred to our hospital. An eschar was identified in the back of It. femur. Treatment included minocycline, ciprofloxain, gabexate mesilate, methylprednisolone, hemodialysis and mechanical ventilation. In spite of the avobe treatment, she died 3 days after admission of the local hospital. Though the serological test showed no positive antibody titer against Rickettsia japonica, Rickettsia japonica was isoleted from blood culture, to confirm Japanese spotted fever, Japanese spotted fever is generaly a curative disease with early diagnosis and minocycline. In this case, the patient died 3 days after proper diagnosis and treatment was started. We reported the second fatal Japanese spotted fever case in Japan.

Topics: Aged; Anti-Bacterial Agents; Ciprofloxacin; Disseminated Intravascular Coagulation; Drug Therapy, Combination; Fatal Outcome; Female; Humans; Japan; Methylprednisolone; Minocycline; Multiple Organ Failure; Renal Dialysis; Respiration, Artificial; Rickettsia; Rickettsia Infections; Severity of Illness Index

Twenty-eight patients with Japanese spotted fever were clinically investigated. The diagnosis was determined by confirming an increase of specific antibody. All patients were treated with minocycline, and all recovered, excluding one patient with a fulminant course. Fever and exanthema were observed in all patients, and an eschar was pointed out in 20 (71%) patients. The platelet count was 10 x 10(4)/microl or lower in 8 (28%) patients. The fibrin degradation product (FDP)-level was abnormally high, 10 microg/ml or more, in 16 (57%) patients. The creatine kinase (CK) value was high in 14 of 22 patients, suggesting the presence of myositis. The leukocyte count, FDP, C-reactive protein, and soluble interleukin 2 receptor (sIL2-R) levels were significantly higher in severe cases. In the group without concomitant steroid therapy, mean times of 54.7 h and 101.4 h were required to reduce the temperature to 38 degrees C and 37 degrees C or lower, respectively, after the initiation of tetracycline treatment. There were 6 severe cases: 1 with disseminated intravascular coagulation, 2 with multiorgan failure, 1 with acute respiratory distress syndrome, and 2 with meningoencephalitis. These severe cases formed a group that required 6 or more days to initiate therapy after the onset (P < 0.005 vs non-severe group), showing that delay in diagnosis and therapy is the major cause of aggravation. In the 2 patients complicated by multiorgan failure, the sIL2-R level, produced by activated lymphocytes, was 10,000 U/ml or higher, suggesting that an sIL2-R level of more than 10,000 U/ml can be used as a marker of poor prognosis. It may be better that moderate to severe cases are treated with minocycline plus short-term steroid therapy.

Topics: Acute Disease; Adolescent; Adult; Aged; Anti-Bacterial Agents; Child; Disseminated Intravascular Coagulation; Female; Humans; Infant, Newborn; Male; Meningoencephalitis; Middle Aged; Minocycline; Multiple Organ Failure; Prevalence; Receptors, Interleukin-2; Respiratory Distress Syndrome, Newborn; Rickettsia; Rickettsia Infections

A 49-year-old man was admitted to our hospital, with a diagnosis of multiple organ failure, on June 10, 2000. Physical examination revealed high fever, generalized maculopapular erythema, and an eschar on his lower leg. Laboratory findings revealed severe renal and liver dysfunction, disseminated intravascular coagulation (DIC), and markedly elevated soluble interleukin 2-receptor (sIL2-R) level (>10 000 U/ml). Administration of minocycline was started immediately, with a diagnosis of rickettsial infection. Simultaneously, anti-thrombin III and heparin were started to treat the DIC, and hemodialysis was also initiated. However, the day after admission, his consciousness level lapsed, to the level of coma, and blood pressure was less than 60 mmHg, indicating shock. Therefore, 500 mg of methylprednisolone was administered once; as a result, rapid pyretolysis and improvement of consciousness disturbance were achieved. Laboratory data indicative of inflammation gradually improved after a few days. Hemodialysis was required ten times. During the recovery period, the level of specific IgM antibody against Rickettsia japonica increased to x2560, and he was diagnosed as having Japanese spotted fever. On July 11, he was discharged without sequelae. The course in our patient was very severe, and treatment with minocycline alone may have resulted in a fatal outcome. The level of sIL2-R, which is produced by activated lymphocytes, was markedly increased. Therefore, markedly elevated lymphocyte activation and hypercytokinemia may have been present on admission. The short-term steroid therapy may have been effective in inhibiting the excessive activation of lymphocytes in the critical stage. In the severe form of Japanese spotted fever with organ failure, combination therapy with minocycline and short-term steroids may be very useful.

Topics: Anti-Bacterial Agents; Anti-Inflammatory Agents; Antibodies, Bacterial; Disseminated Intravascular Coagulation; Humans; Immunoglobulin M; Male; Methylprednisolone; Middle Aged; Minocycline; Multiple Organ Failure; Receptors, Interleukin-2; Rickettsia; Rickettsia Infections; Serologic Tests

A 49-year-old man, who had a 3-year history of liver dysfunction but had not been treated, was admitted to the hospital with a sudden onset of fever and generalized muscle pain. He subsequently developed generalized purpura with scattered hemorrhagic bullae of the skin and massive bloody stools. Aeromonas sobria was proven by culture of both blood and bullous fluid. In spite of the extensive treatment with antibiotics and other medications in the intensive care unit (ICU), the patient went into septic shock and died 2 days after admission. Pathological examination on autopsy revealed segmental necrotizing gastroenteritis with bacterial colonies and alcoholic liver cirrhosis, in addition to extensive severe soft tissue damage involving cellulitis and rhabdomyolysis and epidermolysis. Although the prognosis for Vibrio vulnificus infection with severe soft tissue damage in patients with liver cirrhosis, malignancy, diabetes mellitus or other pre-existing diseases is poor, the unfavorable progression of Aeromonas species, especially A. sobria infection is rare. This is thought to be the first report of an autopsied case.

Topics: Aeromonas; Dopamine; Enterocolitis, Necrotizing; Fatal Outcome; Gastroenteritis; Gram-Negative Bacterial Infections; Humans; Imipenem; Liver Cirrhosis, Alcoholic; Male; Middle Aged; Minocycline; Multiple Organ Failure; Norepinephrine; Shock, Septic; Soft Tissue Infections