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1.
Altern Ther Health Med ; 29(1): 40-43, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36074966

ABSTRACT

Introduction: Nutrition treatment is important in the critically ill patient. Nutritional therapy should be instituted as soon as possible if indicated. Case presentation: A 64-year-old woman with malnutrition and intestinal obstruction with gastrointestinal bleeding came to our emergency room. She had a history of constipation. After CT scan, we found perforations in the digestive tract. Because she could not tolerate surgery and parenteral nutrition (PN), we chose to start enteral nutrition (EN). She recovered after the initiation of EN. Discussion: Chronic constipation may cause intestinal obstruction, which is rare but fatal. Providers should evaluate the nutritional status for the intensive care patient and start PN/EN at once if necessary. EN may help the closure of perforations. Conclusion: EN may play a vital important role even in the patients who have perforations in the digestive tract. Chronic constipation may cause obstruction and perforation, which are rare but fatal.


Subject(s)
Intestinal Obstruction , Intestinal Perforation , Female , Humans , Middle Aged , Nutritional Status , Intestinal Perforation/complications , Intestinal Perforation/surgery , Nutritional Support , Constipation/complications , Constipation/therapy , Intestinal Obstruction/complications , Intestinal Obstruction/diagnostic imaging , Intestinal Obstruction/therapy
2.
J Surg Res ; 252: 231-239, 2020 08.
Article in English | MEDLINE | ID: mdl-32299011

ABSTRACT

BACKGROUND: Standard treatment for diffuse peritonitis due to colorectal perforation may be insufficient to suppress inflammatory reaction in sepsis. Thus, developing new treatments is important. This study aimed to examine whether intraperitoneal irradiation by artificial sunlight suppresses inflammatory reaction in a lipopolysaccharide (LPS)-induced peritonitis model after surgical treatments. MATERIALS AND METHODS: Mice were divided into naive, nontreatment (NT), and phototherapy (PT) groups. In the latter two groups, LPS was intraperitoneally administered to induce peritonitis and removed by intraperitoneal lavage after laparotomy. The PT group was irradiated with artificial sunlight intraperitoneally. We evaluated the local and systemic inflammatory reactions. Murine macrophages were irradiated with artificial sunlight after stimulation by LPS, and cell viability and expression of tumor necrotizing factor-α (TNF-α) were evaluated. RESULTS: As a local inflammatory reaction, the whole cell count, the expression of interleukin-6 and TNF-α in the intra-abdominal fluid, and the peritoneal thickness were significantly lower in the PT group than in the NT group. As a systematic inflammatory reaction, the expression of serum TNF-α, granulocyte macrophage colony-stimulating factor, monocyte chemotactic protein-1, macrophage inflammatory protein (MIP)-1α, and MIP-1ß were significantly lower in the PT group than in the NT group. Irradiation by artificial sunlight suppressed the expression of TNF-α in murine macrophages without affecting cell viability. CONCLUSIONS: Intraperitoneal irradiation by artificial sunlight could suppress local and systemic inflammatory reactions in the LPS-induced peritonitis murine model. These effects may be associated with macrophage immune responses.


Subject(s)
Intestinal Perforation/complications , Peritoneum/radiation effects , Peritonitis/therapy , Phototherapy/methods , Sunlight , Animals , Disease Models, Animal , Humans , Inflammation Mediators/metabolism , Intestinal Perforation/immunology , Lipopolysaccharides/administration & dosage , Lipopolysaccharides/immunology , Macrophages, Peritoneal/immunology , Macrophages, Peritoneal/metabolism , Macrophages, Peritoneal/radiation effects , Male , Mice , Peritoneum/immunology , Peritonitis/immunology , RAW 264.7 Cells
5.
Ann R Coll Surg Engl ; 97(3): e39-42, 2015 Apr.
Article in English | MEDLINE | ID: mdl-26263825

ABSTRACT

Complications following foreign body (FB) ingestion are an uncommon clinical problem. A 59-year-old man presented with a 4-week history of left iliac fossa pain and 1 episode of dark red blood mixed with stools. Inflammatory markers were elevated, and computed tomography (CT) of the abdomen and pelvis showed an ill defined abdominal wall inflammatory collection in close contact with the small bowel loops. He was treated with antibiotics, and follow-up CT, colonoscopy and small bowel enema were mostly unremarkable. The patient presented again ten months later with left iliac fossa cellulitis and fever. Multiplanar CT (the patient's fourth scan) demonstrated a 10cm abdominal wall collection with a linear hyperdense structure in the collection. The radiologists suspected a FB and on close scrutiny of the previous scans, they noted it to have been present on all of them. A targeted incision led to the removal of a 3cm fishbone from the collection. This case highlights the need to consider the possibility of a FB being the underlying cause in any unexplained intra-abdominal or abdominal wall inflammatory process so that the diagnosis is made in a timely manner.


Subject(s)
Abdominal Wall , Abscess/diagnosis , Delayed Diagnosis , Foreign-Body Migration/complications , Intestinal Perforation/complications , Intestine, Small/injuries , Abscess/etiology , Abscess/surgery , Diagnosis, Differential , Drainage/methods , Eating , Foreign-Body Migration/diagnosis , Humans , Intestinal Perforation/diagnosis , Male , Middle Aged , Seafood , Tomography, X-Ray Computed
6.
J Immunol ; 191(12): 6040-51, 2013 Dec 15.
Article in English | MEDLINE | ID: mdl-24249730

ABSTRACT

We currently face an alarming resurgence in infectious diseases characterized by antimicrobial resistance and therapeutic failure. This has generated the urgent need of developing new therapeutic approaches that include agents with nontraditional modes of action. A recent interest focused on approaches based on our natural immune defenses, especially on peptides that combine innate antimicrobial activity against diverse pathogens and immunoregulatory functions. In this study, to our knowledge, we describe for the first time the antimicrobial activity of the neuropeptide urocortin II (UCNII) against a panel of Gram-positive and Gram-negative bacteria and tropical parasites of the genus Leishmania. Importantly, this cytotoxicity was selective for pathogens, because UCNII did not affect mammalian cell viability. Structurally, UCNII has a cationic and amphipathic design that resembles antimicrobial peptides. Using mutants and UCNII fragments, we determined the structural requirements for the interaction between the peptide and the surface of pathogen. Following its binding to pathogen, UCNII caused cell death through different membrane-disrupting mechanisms that involve aggregation and membrane depolarization in bacteria and pore formation in Leishmania. Noteworthily, UCNII killed the infective form of Leishmania major even inside the infected macrophages. Consequently, UCNII prevented mortality caused by polymicrobial sepsis and ameliorated pathological signs of cutaneous leishmaniasis. Besides its presence in body physical and mucosal barriers, we found that innate immune cells produce UCNII in response to infections. Therefore, UCNII could be considered as an ancient highly-conserved host peptide involved in the natural antimicrobial defense and emerge as an attractive alternative to current treatments for microbial disorders with associated drug resistances.


Subject(s)
Corticotropin-Releasing Hormone/physiology , Leishmania/drug effects , Leishmaniasis, Cutaneous/drug therapy , Sepsis/drug therapy , Urocortins/physiology , Amino Acid Sequence , Animals , Cell Membrane/drug effects , Corticotropin-Releasing Hormone/chemistry , Corticotropin-Releasing Hormone/pharmacology , Drug Evaluation, Preclinical , Escherichia coli/drug effects , Female , Humans , Hydrogen Bonding , Immunity, Innate , Intestinal Perforation/complications , Intestinal Perforation/microbiology , Leishmania/ultrastructure , Leishmaniasis, Cutaneous/parasitology , Lipopolysaccharides/chemistry , Macrophages/parasitology , Membrane Potentials/drug effects , Mice, Inbred BALB C , Micrococcus luteus/drug effects , Models, Molecular , Molecular Sequence Data , Peptide Fragments/chemistry , Peptide Fragments/pharmacology , Peptide Fragments/therapeutic use , Peritonitis/etiology , Peritonitis/microbiology , Protein Binding , Protein Conformation , Pseudomonas pseudoalcaligenes/drug effects , Sepsis/etiology , Streptococcus mutans/drug effects , Urocortins/chemistry , Urocortins/pharmacology
7.
Acta Anaesthesiol Scand ; 57(6): 713-8, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23683126

ABSTRACT

BACKGROUND: Increased vascular leakage leading to hypovolaemia and tissue oedema is common in severe sepsis. Hypovolaemia together with oedema formation may contribute to hypoxia and result in multiorgan failure and death. To improve treatment during sepsis, a potential therapeutic target may be to reduce the vascular leakage. Substances affecting the endothelial barrier are interesting in this respect, as it is suggested that increase in vascular leakage depends on reorganisation of the endothelial cells and breakdown of the endothelial barrier. The agonist of the bioactive lipid sphingosine-1-phosphate, FTY720, has been shown to modulate the integrity of the endothelium and reduce permeability both in vitro and in vivo. The aim of the present study was to determine if FTY720 could reduce the loss of plasma volume during experimental sepsis in rats. METHODS: Sepsis was induced by ligation and incision of the caecum in the rat. Plasma volume was determined before and 4.5 h after induction of sepsis by a dilution technique using (125) I-labelled albumin. RESULTS: FTY720 in a dose of 0.2 mg/kg reduced the loss of plasma during sepsis by approximately 30% compared with vehicle, without any adverse effects on haemodynamic and physiological parameters. The increase in hematocrit and haemoglobin concentration was also found to be higher in the vehicle group. CONCLUSION: FTY720 in a dose without haemodynamic side effects reduces loss of plasma volume during experimental sepsis most likely because of reduction in permeability and may therefore be beneficial in sepsis.


Subject(s)
Lysophospholipids/agonists , Plasma Volume/drug effects , Propylene Glycols/therapeutic use , Sepsis/physiopathology , Sphingosine/analogs & derivatives , Animals , Capillary Leak Syndrome/drug therapy , Capillary Leak Syndrome/etiology , Capillary Permeability/drug effects , Cecum/injuries , Disease Models, Animal , Diuresis/drug effects , Drug Evaluation, Preclinical , Edema/etiology , Edema/prevention & control , Endothelium, Vascular/drug effects , Fingolimod Hydrochloride , Hematocrit , Hemodynamics/drug effects , Hemoglobins/analysis , Intestinal Perforation/complications , Male , Propylene Glycols/pharmacology , Random Allocation , Rats , Rats, Sprague-Dawley , Sepsis/blood , Sepsis/etiology , Sphingosine/agonists , Sphingosine/pharmacology , Sphingosine/therapeutic use
8.
World J Gastroenterol ; 19(18): 2752-60, 2013 May 14.
Article in English | MEDLINE | ID: mdl-23687412

ABSTRACT

AIM: To retrospectively review the results of over-the-scope clip (OTSC) use in our hospital and to examine the feasibility of using the OTSC to treat perforations after endoscopic submucosal dissection (ESD). METHODS: We enrolled 23 patients who presented with gastrointestinal (GI) bleeding, fistulae and perforations and were treated with OTSCs (Ovesco Endoscopy GmbH, Tuebingen, Germany) between November 2011 and September 2012. Maximum lesion size was defined as lesion diameter. The number of OTSCs to be used per patient was not decided until the lesion was completely closed. We used a twin grasper (Ovesco Endoscopy GmbH, Tuebingen, Germany) as a grasping device for all the patients. A 9 mm OTSC was chosen for use in the esophagus and colon, and a 10 mm device was used for the stomach, duodenum and rectum. The overall success rate and complications were evaluated, with a particular emphasis on patients who had undergone ESD due to adenocarcinoma. In technical successful cases we included not only complete closing by using OTSCs, but also partial closing where complete closure with OTSCs is almost difficult. In overall clinical successful cases we included only complete closing by using only OTSCs perfectly. All the OTSCs were placed by 2 experienced endoscopists. The sites closed after ESD included not only the perforation site but also all defective ulcers sites. RESULTS: A total of 23 patients [mean age 77 years (range 64-98 years)] underwent OTSC placement during the study period. The indications for OTSC placement were GI bleeding (n = 9), perforation (n = 10), fistula (n = 4) and the prevention of post-ESD duodenal artificial ulcer perforation (n = 1). One patient had a perforation caused by a glycerin enema, after which a fistula formed. Lesion closure using the OTSC alone was successful in 19 out of 23 patients, and overall success rate was 82.6%. A large lesion size (greater than 20 mm) and a delayed diagnosis (more than 1 wk) were the major contributing factors for the overall unsuccessful clinical cases. The location of the unsuccessful lesion was in the stomach. The median operation time in the successful cases was 18 min, and the average observation time was 67 d. During the observation period, none of the patients experienced any complications associated with OTSC placement. In addition, we successfully used the OTSC to close the perforation site after ESD in 6 patients. This was a single-center, retrospective study with a small sample size. CONCLUSION: The OTSC is effective for treating GI bleeding, fistulae as well as perforations, and the OTSC technique proofed effective treatment for perforation after ESD.


Subject(s)
Dissection/adverse effects , Endoscopy, Gastrointestinal/adverse effects , Gastrointestinal Hemorrhage/surgery , Hemostasis, Endoscopic/instrumentation , Natural Orifice Endoscopic Surgery/instrumentation , Postoperative Hemorrhage/surgery , Surgical Instruments , Aged , Aged, 80 and over , Digestive System Fistula/complications , Equipment Design , Feasibility Studies , Female , Gastrointestinal Hemorrhage/etiology , Hemostasis, Endoscopic/adverse effects , Humans , Intestinal Perforation/complications , Male , Middle Aged , Natural Orifice Endoscopic Surgery/adverse effects , Postoperative Hemorrhage/etiology , Retrospective Studies , Risk Factors , Treatment Outcome
9.
Ned Tijdschr Geneeskd ; 155(42): A2797, 2011.
Article in Dutch | MEDLINE | ID: mdl-22027453

ABSTRACT

A 78-year-old man presented with obstipation, abdominal pain and fever. An abdominal CT-scan demonstrated a collection of gas in the mesorectal fascia. A sigmoidoscopy showed a linear defect in the mucous membrane and a haematoma. The patient stated he had rectally applied a thermometer as well as several enemas. The symptoms were caused by a traumatic perforation.


Subject(s)
Abdominal Pain/diagnosis , Enema/adverse effects , Fever/diagnosis , Intestinal Perforation/complications , Intestinal Perforation/diagnosis , Abdominal Pain/etiology , Aged , Fever/etiology , Humans , Male , Tomography, X-Ray Computed
10.
Kaohsiung J Med Sci ; 27(6): 234-8, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21601169

ABSTRACT

The objective of this article is to discuss and report three cases of right colon perforation secondary to postcesarean Ogilvie's syndrome (OS; colonic pseudo-obstruction) requiring right hemicolectomy. We retrospectively reviewed the case notes of three patients who underwent caesarean section and postoperatively developed OS. OS is an uncommon problem in patients undergoing caesarean section. Abdominal X-ray and water-soluble contrast enema are the main diagnostic modalities. Drip-suck therapy along with endoscopic or pharmacological decompression should be performed in early stages. In a significant percentage of patients, diagnosis is delayed resulting in bowel ischemia and perforation requiring surgical resection and adding significant mortality/morbidity. We recommend our obstetric colleagues to involve surgical team in earlier stages to avoid surgery-related mortality and morbidity. We also advocate general surgeons to be aware of OS in patients after caesarean section and recommend a stepwise systematic approach toward the diagnosis and management of OS.


Subject(s)
Cesarean Section/adverse effects , Colon/pathology , Colonic Pseudo-Obstruction/complications , Colonic Pseudo-Obstruction/etiology , Intestinal Perforation/complications , Intestinal Perforation/etiology , Adult , Colon/diagnostic imaging , Colonic Pseudo-Obstruction/diagnostic imaging , Enema , Female , Humans , Intestinal Perforation/diagnostic imaging , Pregnancy , Preoperative Care , Radiography, Abdominal , Tomography, X-Ray Computed , Young Adult
11.
Tumori ; 97(6): 794-9, 2011.
Article in English | MEDLINE | ID: mdl-22322848

ABSTRACT

There are no effective conventional systemic cytotoxic therapies for patients with unresectable or advanced hepatocellar carcinoma (HCC). Sorafenib, an oral multi-targeted tyrosine kinase inhibitor, was recently approved for the treatment of patients with HCC. Sorafenib is generally well tolerated and has an acceptable toxicity profile.Gastrointestinal perforation is a rare adverse event. We present a case of transverse colon perforation during sorafenib therapy for advanced HCC. A 68-year-old woman with advanced HCC was treated with sorafenib. Eight weeks later the patient presented with the sudden onset of sharp abdominal pain. Emergency surgery was performed for panperitonitis and a perforation involving the transverse colon.


Subject(s)
Antineoplastic Agents/adverse effects , Benzenesulfonates/adverse effects , Carcinoma, Hepatocellular/drug therapy , Colonic Diseases/chemically induced , Colonic Diseases/diagnosis , Intestinal Perforation/chemically induced , Intestinal Perforation/diagnosis , Liver Neoplasms/drug therapy , Protein Kinase Inhibitors/adverse effects , Pyridines/adverse effects , Abdominal Pain/etiology , Aged , Antineoplastic Agents/administration & dosage , Benzenesulfonates/administration & dosage , Colon, Transverse/blood supply , Colon, Transverse/drug effects , Colonic Diseases/complications , Colonic Diseases/pathology , Colonic Diseases/surgery , Female , Humans , Intestinal Perforation/complications , Intestinal Perforation/pathology , Intestinal Perforation/surgery , Ischemia/chemically induced , Ischemia/complications , Niacinamide/analogs & derivatives , Peritonitis/complications , Peritonitis/etiology , Peritonitis/surgery , Phenylurea Compounds , Protein Kinase Inhibitors/administration & dosage , Pyridines/administration & dosage , Sorafenib , Tomography, X-Ray Computed
12.
Gastrointest Endosc Clin N Am ; 20(2): 279-91, 2010 Apr.
Article in English | MEDLINE | ID: mdl-20451817

ABSTRACT

Computed tomographic colonography (CTC) has emerged as an alternative screening tool for colorectal cancer due to the potential to provide good efficacy combined with greater acceptability than optical colonoscopy or fecal occult blood testing. However, some organizations have raised concerns about the potential harms, including perforation rates and radiation-related cancer risks, and have not recommended that it currently be used as a screening tool in the general population in the US. In this article the authors review the current evidence for these potential harms from CTC and compare them to the potential harms from the alternatives including colonoscopy and double-contrast barium enema.


Subject(s)
Colon/injuries , Colonography, Computed Tomographic/adverse effects , Intestinal Perforation/complications , Radiation Injuries/etiology , Colon/radiation effects , Colorectal Neoplasms/diagnostic imaging , Humans , Incidence , Intestinal Perforation/epidemiology , Radiation Injuries/epidemiology , Radiation Injuries/prevention & control , Risk Factors , Rupture , United States/epidemiology
13.
Acta pediátr. costarric ; 22(1): 34-39, ene.-abr. 2010. ilus
Article in Spanish | LILACS | ID: lil-648330

ABSTRACT

Objetivo: El objetivo general del estudio fue describir todos los casos documentados de invaginación intestinal en niños menores de 24 meses en el HNN durante el periodo 2001-2008. Métodos: estudio retrospectivo y descriptivo, basado en la información de expedientes clínicos y del Servicio de Estadística, de todos los egresos hospitalarios con el diagnóstico de invaginación intestinal en niños menores de 24 meses durante el periodo: enero 2001 a diciembre 2008. Resultados: durante este periodo de estudio la media de la tasa de incidencia de invaginación intestinal en el HNNH fue de 31 por cada 100000 nacidos vivos. La distribución de pacientes por sexo y grupo de edad fue: 57.7 por ciento hombres y 42.3 por ciento mujeres, p:0.003. El 85.2 por ciento de los episodios de invaginación intestinal ocurrió en niños menores de 12 meses, 14.8 por ciento de 12 a 24 meses, 27/182 pacientes. La edad media de presentación fue de 7.7 meses. 103 pacientes requirieron ser llevados a sala de operaciones para desinvaginación por taxis, de los cuales el 79.61 por ciento, 82, tuvieron un colon por enema fallido. La perforación intestinal fue la complicación más frecuente en un 12.6 por ciento de los casos, 13. Se realizó resección intestinal en 16 casos, 15.50 por ciento. Conclusiones: este estudio brinda información sobre la epidemiología de la invaginación intestinal en Costa Rica siendo éste un estudio base para futuras investigaciones asociadas a la introducción de las vacunas del rotavirus en el esquema de vacunación del país.


Subject(s)
Humans , Male , Female , Infant, Newborn , Infant , Intussusception/surgery , Intussusception/classification , Intussusception/diagnosis , Intussusception/epidemiology , Intussusception/therapy , Pediatrics , Intestinal Perforation/surgery , Intestinal Perforation/complications , Intestinal Perforation/diagnosis , Intestinal Perforation/therapy , Costa Rica
14.
Ai Zheng ; 28(9): 908-12, 2009 Sep.
Article in Chinese | MEDLINE | ID: mdl-19728905

ABSTRACT

BACKGROUND AND OBJECTIVE: Prognosis of stage II colorectal cancer varies. Whether or not to perform adjuvant chemotherapy on patients with stage II colorectal cancer is controversial. This study was to explore the prognostic factors for the patients with stage II colorectal cancer and evaluate the effect and the necessity of adjuvant chemotherapy. METHODS: Between January 2000 and January 2005, 443 patients with stage II colorectal cancer receiving radical surgery at Sun Yat-sen University Cancer Center were retrospectively analyzed. The overall survival rate and survival curve were analyzed using the Kaplan-Meier method and the log-rank test. The univariate and multivariate prognostic analyses were performed by the Cox regression model. Patients with or without chemotherapy (Xelox/Folfox regimen) with high-risk factors were analyzed respectively. RESULTS: The median follow-up time was 59 months, and the 3-and 5-year survival rates were 88.4% and 82.5%, respectively. Univariate analysis showed that intestinal obstruction or perforation, diabetes mellitus, inadequate surgical margin, and the number of sampled nodes < 9 were poor prognostic factors. Patients with intestinal obstruction or perforation, the number of sampled nodes < 9 achieved higher 5-year survival (80% and 86%) undergoing adjuvant chemotherapy than those receiving surgery alone (67% and 64%). CONCLUSIONS: The prognosis of colorectal cancer patients with intestinal obstruction or perforation, diabetes mellitus, inadequate surgical margin, and the number of sampled nodes < 9 are relatively poor. Adjuvant chemotherapy is recommended to patients with intestinal obstruction, perforation or sampled nodes < 9.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colonic Neoplasms/drug therapy , Rectal Neoplasms/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Capecitabine , Chemotherapy, Adjuvant , Child , Colonic Neoplasms/complications , Colonic Neoplasms/pathology , Colonic Neoplasms/surgery , Deoxycytidine/analogs & derivatives , Deoxycytidine/therapeutic use , Female , Fluorouracil/analogs & derivatives , Fluorouracil/therapeutic use , Follow-Up Studies , Humans , Intestinal Obstruction/complications , Intestinal Perforation/complications , Leucovorin/therapeutic use , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Staging , Organoplatinum Compounds/therapeutic use , Oxaloacetates , Proportional Hazards Models , Rectal Neoplasms/complications , Rectal Neoplasms/pathology , Rectal Neoplasms/surgery , Retrospective Studies , Survival Rate , Young Adult
15.
J Chemother ; 21(2): 170-80, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19423470

ABSTRACT

This prospective, randomized, open, international, multicenter study of adults with complicated intra-abdominal infections (cIAI) compared the efficacy and safety of sequential intravenous (i.v.) to oral (p.o.) moxifloxacin 400 mg once daily, with that of i.v. ceftriaxone 2 g once daily, plus metronidazole 500 mg three times daily, followed by p.o. amoxicillin/clavulanate 625 mg three times daily. The primary efficacy variable was clinical cure at test of cure (TOC) (day 28-42 after study entry) in the per protocol (PP) population. Of 595 patients in the study, 511 patients were valid for PP analysis (246 moxifloxacin, 265 ceftriaxone/metronidazole). Sequential moxifloxacin was noninferior to the comparator regimen--clinical cure rates at TOC were 80.9% versus 82.3% (moxifloxacin versus ceftriaxone/metronidazole; 95% CI -8.9, 4.2%). The incidence of adverse events was comparable between the two treatment groups. Therefore, sequential moxifloxacin monotherapy is as effective and safe as combination therapy with i.v. ceftriaxone plus i.v. metronidazole followed by oral amoxicillin/clavulanate for the treatment of cIAI.


Subject(s)
Anti-Infective Agents/administration & dosage , Aza Compounds/administration & dosage , Bacterial Infections/drug therapy , Gastrointestinal Diseases/drug therapy , Quinolines/administration & dosage , Abdominal Abscess/drug therapy , Administration, Oral , Adult , Aged , Amoxicillin-Potassium Clavulanate Combination/administration & dosage , Amoxicillin-Potassium Clavulanate Combination/adverse effects , Anti-Infective Agents/adverse effects , Appendicitis/complications , Appendicitis/drug therapy , Aza Compounds/adverse effects , Bacterial Infections/etiology , Ceftriaxone/administration & dosage , Ceftriaxone/adverse effects , Drug Therapy, Combination , Female , Fluoroquinolones , Gastrointestinal Diseases/microbiology , Humans , Infusions, Intravenous , Intestinal Perforation/complications , Intestinal Perforation/drug therapy , Male , Metronidazole/administration & dosage , Metronidazole/adverse effects , Microbial Sensitivity Tests , Middle Aged , Moxifloxacin , Peritonitis/drug therapy , Prospective Studies , Quinolines/adverse effects
18.
Ann Surg ; 244(2): 204-11, 2006 Aug.
Article in English | MEDLINE | ID: mdl-16858182

ABSTRACT

OBJECTIVE: To compare the safety and efficacy of sequential intravenous (IV) to oral (PO) moxifloxacin treatment against a standard antimicrobial regimen of IV piperacillin-tazobactam followed by PO amoxicillin-clavulanate for the treatment of adults with complicated intra-abdominal infection (cIAI). SUMMARY BACKGROUND DATA: cIAIs are commonly due to mixed aerobic and anaerobic bacteria and require both source control and broad-spectrum antibiotic therapy. METHODS: A prospective, double-blind, randomized, phase III comparative trial. Patients with cIAI were stratified by disease severity (APACHE II score) and randomized to either IV/PO moxifloxacin (400 mg q24 hours) or comparator (IV piperacillin-tazobactam [3.0/0.375 g q6 hours] +/- PO amoxicillin-clavulanate [800 mg/114 mg q12 hours]), each for 5 to 14 days. The primary efficacy variable was clinical cure rate at the test-of-cure visit (days 25-50). Bacteriologic outcomes were also determined. RESULTS: : Of 656 intent-to-treat patients, 379 (58%) were valid to assess efficacy (183 moxifloxacin, 196 comparator). Demographic and baseline medical characteristics were similar between the 2 groups. Clinical cure rates at test-of-cure were 80% (146 of 183) for moxifloxacin versus 78% (153 of 196) for comparator (95% confidence interval, -7.4%, 9.3%). The clinical cure rate at test-of-cure for hospital-acquired cIAI was higher with moxifloxacin (82%, 22 of 27) versus comparator (55%, 17 of 31; P = 0.05); rates were similar for community-acquired infections (80% [124 of 156] versus 82% [136 of 165], respectively). Bacterial eradication rates were 78% (117 of 150) with moxifloxacin versus 77% (126 of 163) in the comparator group (95% confidence interval, -9.9%, 8.7%). CONCLUSIONS: Once daily IV/PO moxifloxacin monotherapy was as least as effective as standard IV piperacillin-tazobactam/PO amoxicillin-clavulanate dosed multiple times daily for the treatment of cIAIs.


Subject(s)
Abdominal Abscess/drug therapy , Amoxicillin-Potassium Clavulanate Combination/therapeutic use , Anti-Bacterial Agents/therapeutic use , Aza Compounds/therapeutic use , Bacterial Infections/drug therapy , Quinolines/therapeutic use , Abdominal Abscess/microbiology , Administration, Oral , Adult , Anti-Bacterial Agents/administration & dosage , Appendicitis/complications , Aza Compounds/administration & dosage , Cross Infection/drug therapy , Double-Blind Method , Female , Fluoroquinolones , Gram-Negative Bacterial Infections/drug therapy , Gram-Positive Bacterial Infections/drug therapy , Humans , Injections, Intravenous , Intestinal Perforation/complications , Male , Middle Aged , Moxifloxacin , Penicillanic Acid/analogs & derivatives , Penicillanic Acid/therapeutic use , Piperacillin/therapeutic use , Piperacillin, Tazobactam Drug Combination , Prospective Studies , Quinolines/administration & dosage , Safety , Stomach Rupture/complications , Treatment Outcome
20.
FASEB J ; 18(11): 1185-91, 2004 Aug.
Article in English | MEDLINE | ID: mdl-15284218

ABSTRACT

The pathophysiology of sepsis involves excessive lymphocyte apoptosis, which correlates with adverse outcomes, and disordered cytokine production, which may promote host injury. As the protease inhibitor (PI) class of antiretroviral agents is known to prevent apoptosis in vitro, we evaluated their effect on survival, lymphocyte apoptosis, and consequent cytokine production in mice with sepsis induced by cecal ligation and perforation. Mice pretreated with PIs have improved survival (67%; P<0.0005) compared with controls (17%) and a significant (P<0.05) reduction in lymphocyte apoptosis. Even mice receiving therapy beginning 4 h after perforation demonstrated improved survival (50%; P<0.05) compared with controls. PI therapy is also associated with an increase in the Th1 cytokine TNF-alpha (P<0.05) early in sepsis and a reduction in the Th2 cytokines IL-6 and IL-10 (P<0.05) late in sepsis; despite no intrinsic antibacterial effects, PI also reduced quantitative bacterial blood cultures. The beneficial effects of PI appear to be specific to lymphocyte apoptosis, as lymphocyte-deficient Rag1-/- mice did not experience benefit from treatment with PI. Thus, inhibition of lymphocyte apoptosis by PI is a candidate approach for the treatment of sepsis.


Subject(s)
Apoptosis/drug effects , Nelfinavir/therapeutic use , Protease Inhibitors/therapeutic use , Sepsis/drug therapy , Administration, Oral , Animals , Cecum/injuries , Cytokines/blood , Drug Evaluation, Preclinical , Enterococcus/drug effects , Escherichia coli/drug effects , Female , Genes, RAG-1 , Germ-Free Life , Intestinal Perforation/complications , Lymphocytes/drug effects , Lymphocytes/pathology , Mice , Mice, Inbred C57BL , Mice, Knockout , Microbial Sensitivity Tests , Nelfinavir/administration & dosage , Nelfinavir/pharmacokinetics , Nelfinavir/pharmacology , Protease Inhibitors/administration & dosage , Protease Inhibitors/pharmacokinetics , Protease Inhibitors/pharmacology , Pseudomonas aeruginosa/drug effects , Ritonavir/administration & dosage , Ritonavir/pharmacokinetics , Sepsis/blood , Sepsis/pathology , Spleen/drug effects , Spleen/pathology , Streptococcus bovis/drug effects , Thymus Gland/drug effects , Thymus Gland/pathology
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