Triple Antimicrobial Therapy Research Articles

Randomized, Double-Blind, Placebo-Controlled Study of Anti-Mycobacterial Therapy (RHB-104) in Active Crohn's Disease.

This study, conducted between 4 October 2013, and 30 November 2018, tested the hypothesis that triple antimicrobial therapy, targeting Mycobacterium avium subspecies paratuberculosis (MAP), long considered a putative cause, would favorably affect Crohn's disease. A double-blind multicenter study of adults with active Crohn's disease, (i.e., Crohn's Disease Activity Index [CDAI] 220-450 plus C-reactive protein ≥ 1.0 mg/dL, fecal calprotectin (FCP) >162.9 µg/g stool, or recent endoscopic or radiographic confirmation of active disease) receiving concomitant standard-of-care Crohn's disease treatment (Clinicaltrials.gov: NCT01951326) were stratified by anti-tumor necrosis factor use and randomized (1:1) to anti-MAP RHB-104 (clarithromycin 95 mg, rifabutin 45 mg, and clofazimine 10 mg per capsule) (n = 166), resulting in clarithromycin 950 mg/day, rifabutin 450 mg/day, and clofazimine 100 mg/day, or placebo (n = 165) for up to 52 weeks. A greater proportion of RHB-104 versus placebo-treated patients met the primary endpoint-remission (i.e., CDAI < 150)-at week 26 (36.7% [61/166] vs. 22.4% [37/165], respectively; 95% CI for difference: 4.6, 24.0, p = 0.0048; chi-square test). Clinical response (reduction of CDAI by ≥100 points from baseline) at week 26 (first secondary endpoint) was also higher among the patients treated with RHB-104 (73/166 [44.0%]) compared with placebo (50/165 [30.3%]; 95% CI for difference: 3.4, 24.0, p = 0.0116), and it remained higher at week 52 among the patients treated with RHB-104 (59/166 [35.5%] vs. (35/165 [21.2%] for placebo; 95% CI for difference: 4.7, 23.9, p = 0.0042). A statistically significantly greater decline in FCP (another prospective efficacy endpoint) was also observed in RHB-104-treated patients, compared with placebo, at weeks 12, 26, and 52. The rates of serious adverse events were similar between groups (RHB-104: 18.7%; placebo: 18.8%). No patient died during the study. Antimicrobial therapy directed against MAP resulted in significantly greater improvement in clinical and laboratory (FCP) measures of active Crohn's disease.

Antimicrobial Prophylaxis in Lower Uterine Segment Caesarean Section: A Prospective Observational Data-based Study

Introduction: Any major surgery like lower uterine Caesarean Section (CS) can be hazardous due to postoperative nosocomial infection. Pregnant mothers are at greater risk during such surgical intervention as compared to vaginal delivery. Prophylactic antibiotic administration is a standard practice across the globe to prevent such anticipated postoperative infection. Aim: To evaluate the prophylactic antimicrobial use with regards to the choice of antimicrobials, dose, route, timing and duration, any possible Adverse Drug Reaction (ADR) as well as to assess the frequency of the postoperative morbidity due to infection (if any). Materials and Methods: A prospective observational databased study was conducted in the Department of Pharmacology in collaboration with Department of Obstetrics and Gynaecology, Burdwan Medical College and Hospital, Burdwan, West Bengal, India, from February 2016 to October 2017. Study was conducted on 1944 pregnant women of reproductive age group planned or scheduled for elective/emergency lower segment CS, but otherwise healthy and received prophylactic antimicrobials for the surgery. They were prospectively observed regarding the treatment they received with focus on antimicrobial agents from the period of antimicrobial prophylaxis during their stay at hospital to till their discharge. Demographic data, vital signs, indication of CS, postoperative infections and ADR if any were recorded in predesigned proforma. The study population was divided into two groups: group A included 995 mothers, who received ceftriaxone sodium (1 g intravenously) and metronidazole (15 mg/kg) infusion and group B included 949 mothers, who received ampicillin (2 g intravenously), metronidazole (15 mg/kg) infusion and injection gentamycin (5 mg/kg) for 0.5 hour before initiation of CS. The data were statistically analysed by standard statistical software Microsoft Excel 2010 and Statistical Package for the Social Sciences (SPSS) sotware version 27.0 (SPSS Inc., Chicago, IL, USA) expressed as mean and standard deviation and percentage. Independent t- test and Chi-square test were used for analysis. Results: The mean age of group A was 22.36±3.07 years and group B was 22.76±2.47 years. Endomyometritis was documented in 4 (0.4%) from group A and 2 (0.21%) from the group B. Wound infection was present in 3 (0.3%) for group A and five (0.5%) for the group B. Infection related complications like chest infection seen in 7 (0.7%) for group A and in 3 (0.31%) for group B and urinary tract infection was noticed in 6 (0.6%) for group A and 5 (0.52%) for group B. Any incidence of maternal mortality was not evident among the two study groups and statistically insignificant ADR like vomiting and maculopapular rash (p-value=0.324) was observed in both the study groups with the use of above-mentioned antimicrobial therapy. Conclusion: Prophylactic use of ceftriaxone plus metronidazole and combination of triple antimicrobial therapy of ampicillin, metronidazole, and gentamycin therapy at the usual standard dose were commonly used antimicrobials at the present set up and they are safe and equally effective in decreasing considerably the incidence of post caesarean maternal infection thereby reducing their morbidity and mortality

Study of prescribing pattern of antimicrobials in a tertiary care hospital

Background: Antimicrobials are routinely prescribed in several disease conditions in which infections are established or suspected to be the reason for the illness. Excessive and irrational use of antimicrobials leads to development of drug resistance in microorganisms, besides increasing health-care expenditure. Antimicrobial resistance (AMR) leads to increase in morbidity and mortality. The rational use of antimicrobials is a major health need in all countries. Hence, assessment of prescribing pattern of antimicrobials is essential for clinical, educational, and economic purposes. Aims and Objectives: The objectives of the study were to evaluate and compare the prescribing pattern of antimicrobials by assessing – (i) commonly used antimicrobials; and (ii) disease conditions for which they were prescribed. Materials and Methods: It was a prospective observational study done for a period of 1 month. All the prescriptions in which antimicrobials were prescribed in the outpatient departments (OPD) and in-patient wards (IP) were included in the study. Prescriptions were analyzed for demographic and antibiotic data. Results: 1092 prescriptions were collected and analyzed. Among them, 690 prescriptions were from OPD and 382 prescriptions from in patient wards. Out patient data: Cefixime (21.30%) was commonly prescribed followed by fixed dose combination of Amoxicillin + Clavulanic acid (14.64%) and Ciprofloxacin (8.84%). Cefixime was commonly prescribed for URTI (13.43%). Oral route (82.17%) was the preferred route of administration. IP data: Cefotaxime (26.45%) was commonly prescribed followed by fixed dose combination of Piperacillin + Tazobactum (15.29%) and Ceftriaxone (14.46%). Cefotaxime was commonly prescribed preoperatively for most of the surgeries (76.56%). Intravenous route (46.86%) was the preferred route of administration. Single antimicrobial therapy (81.41%) was preferred followed by double (17.80%) and triple (0.79%) antimicrobial therapy. Conclusion: Cefixime and cefotaxime were commonly used in OPD and in patient wards, respectively. Oral route and intravenous route were the preferred route in OPD and IP wards, respectively. Single antimicrobial therapy was commonly preferred in both IP and out-patient wards. Although double and triple antimicrobial therapy was prescribed in small number of patients, it should be cautiously used to prevent AMR.

Chronic lung sepsis in a sample of Egyptian patients with type II diabetes mellitus

Background/aim Chronic lung sepsis is one of the major causes of chronic respiratory symptoms such as chronic cough and pus formation. It has received very little attention over recent decades. In addition, failure of its characterization in immunocompromised patients such as diabetics has led to under-recognition and lack of early management. Patients and methods In this study, 61 patients with symptoms and signs of chronic lung disease were enrolled from Ahmed Maher Teaching Hospital in Egypt. Of them, 32 fulfilling the criteria of chronic lung sepsis were classified into two groups: diabetic (17 patients) and nondiabetic (15 patients). All of the patients were subjected to detailed medical history, thorough clinical examination, laboratory investigations, sputum culture and sensitivity, and high-resolution computed tomography of the chest. Results A total of 23 cases were diagnosed as bronchiectasis, four cases were diagnosed as lung abscess, two cases were pyopneumothorax, whereas there was one case each of infected cyst, empyema, and infected emphysematous bullous. Sputum culture showed that gram-negative organisms were more evident in the diabetic group. The management of cases of chronic lung sepsis showed the use of double or triple antimicrobial therapy in the diabetic group. Conclusion Targeting good control of pneumonia in patients with type II diabetes mellitus using double or triple antimicrobial therapy is essential to inhibit the progression of pulmonary infections to chronic lung sepsis.

Effect of triple antimicrobial therapy on electrocardiography parameters in patients with mild-to-moderate coronavirus disease 2019.

The effects of treatment of coronavirus disease 2019 (COVID-19) with a triple combination composed of hydroxychloroquine, an an-tiviral, and an antibiotic on electrocardiography (ECG) parameters in patients with mild-to-moderate symptoms are not wholly understood. We aimed to explore the changes in ECG parameters after treatment with triple combination therapy in patients with mild-to-moderate symptomatic COVID-19. This retrospective, single-center case series analyzed 91 patients with mild-to-moderate symptomatic COVID-19 at Ankara Gazi Mus-tafa Kemal State Hospital of Ankara City, Turkey, from April 1, 2020, to April 30, 2020. Forty-three patients were treated with hydroxychloroquine+oseltamivir+azithromycin (Group 1) and 48 patients were treated with hydroxychloroquine+oseltamivir+levofloxacin (Group 2). Heart rate, P wave duration, P wave dispersion, PR interval, QRS duration, corrected QT interval (QTc), QTc dispersion (QTD), delta QTc, Tp-e, Tp-e dispersion, and Tp-e/QTc ratio were all calculated from the baseline and posttreatment 12-lead ECG recordings. The QTc, QRS duration, Tp-e, PR interval, and P wave duration were significantly increased after treatment (p<0.001; p<0.001; p<0.001; p=0.001; p=0.001). The posttreatment C-reactive protein level was significantly lower than at baseline in Group 1 (p=0.014). At admission, 30% of patients had QT prolongation, and 4.3% of them had a QT duration >500 ms. Both Group 1 and Group 2 showed significant prolongation of the QTc interval (Group 1; p<0.001 vs. Group 2; p<0.001), QRS duration (Group 1; p=0.006 vs. Group 2; p=0.014), Tp-e (Group 1; p=0.036 vs. Group 2; p<0.001), and PR interval (Group 1; p=0.002 vs. Group2; p=0.05). The QTD was significantly decreased in Group 1 (p<0.001). None of the patients experienced any overt ventricular arrhythmia. To the best of our knowledge, this study is the first to investigate QT prolongation in a population of COVID-19 patients treated with triple combination therapy. We found that there was a significant decrease in the QTD after the treatment in patients who were taking triple therapy including azithromycin.

Small Animal Review

Summary: Feline ocular mycobacteriosis is a treatable disorder, with good clinical outcomes where enucleation is combined with long-term dual or triple antimicrobial therapy.

Neonatal Cellulitis

Introduction: Newborn cellulitis is rare and often atypical disease. It is a diagnostic and therapeutic emergency and its progress leads to instant death. We report three cases of neonatal cellulitis from the Neonatal ICU Department of Mohammed VI university hospital in Marrakesh, highlighting this rare, serious and unknown disease. Case 1: 17-day-old female newborn admitted for sepsis and breast refusal since 5 days. Clinical examination revealed a hypotonic newborn, hypothermic at 34.2 °C with sclerema neonatorum. Skin examination found Erythema and edema on the left hemi-face with necrosis of the ipsilateral nostril. The blood culture had isolated coagulase-negative staphylococci. The newborn was put under triple antimicrobial therapy of 3rd Generation Cephalosporin (3GCs), gentamicin and vancomycin with good progress. Case 2: 20-day-old male newborn, was circumcised ten days before admission, had sepsis with a fever at 40 °C evolving since 24h. The clinical examination found hard, hot and very painful inflammatory lesion starting at the scrotum and extending to suprapubic region and the start of the lower limbs. Blood tests revealed strongly positive infectious status. The progress was positive when put under triple antimicrobial therapy. Case 3: 25-day-old female newborn, visited a traditional healer who gave her a mixture of unknown nature to apply on her face, hospitalized in our department for cellulitis of the right hemi-face extending to the periorbital and cervical region evolving since two days together with a fever. Infectious blood assessment was positive. The progress was favorable when put under triple antimicrobial therapy. Conclusion: Cellulitis is a rare disease in newborn and it must be diagnosed early because it can be complicated into sepsis. The search for other localizations, mainly meningeal, is essential.

Therapy-resistant septic olecranon bursitis due to Mycobacterium gordonae.

Introduction: Septic olecranon bursitis due to atypical mycobacteria is rare. An insidious beginning can delay diagnosis and treatment. Antibacterial therapy recommendations are not well-defined for bursitis caused by atypical mycobacteria. We present a rare case of olecranon bursitis caused by Mycobacterium gordonae, reporting our experiences regarding pathogen identification and antibiotic therapy, which differs from regimes used in common septic bursitis mostly caused by staphylococcus aureus. Methods: A 35-year-old male with bursitis olecrani received open bursectomy. Microbiological culture did not reveal bacteria. Due to wound healing complications revision surgery was performed four weeks postoperatively. Finally, Mycobacterium gordonae was identified by PCR and an antibiogram could be developed. A triple antimicrobial combination therapy with Rifampicin, Clarithromycin, and Ethambutol was administered systemically for 12 months. The patient was followed-up for 24 months. Results: After the second operation with pathogen identification and antibiotic combination therapy the wound healed without any additional complications. At last follow-up 24 months after the first surgery with bursectomy and 23 months after revision surgery with debridement, the patient was still pain free with no significant clinical findings or tenderness to touch at the operation site. Elbow range of motion was full. Discussion: As septic bursitis can be caused by many different and sometimes rare and difficult to identify bacteria, intraoperative probes should be taken and histopathological and microbiological analysis should be conducted, including PCR. In a young man with olecranon bursitis due to Mycobacterium gordonae surgical treatment and an antibiotic combination therapy showed a good clinical outcome after one and two years.

Complicated Varicella Infection at 8-year-old Boy with Pulmonary Agenesis

SUMMARYCONFLICT OF INTEREST: none declared.IntroductionVaricella or chickenpox is highly contagious, childhood infectious disease caused by primary infection with varicella – zoster virus from the herpes family of viruses. Usually it has a mild clinical course, rarely with described complication, mostly affecting respiratory tract and rarely the central nervous system.Case reportThe case present 8 year old boy hospitalized eighth day of disease with clinical pictures of varicella complication. Upon receipt tachydyspnea, high fever, tachycardia, hypotensive with positive findings on lung auscultation in the sense of pneumonia. Extremely high values of non-specific inflammatory parameters are implied on bacterial infection which is treated using triple antimicrobial therapy and antiviral. A detailed clinical, laboratory and radiological evaluation is determined of clinical disease complication under a picture of MODS that required prolonged multidisciplinary treatment in ICU.ConclusionThe disease had a favorable clinical outcome in terms of training completely without consequences but, with the detected congenital absence lower lobe of right lung and transposition of the brachiocephalic trunk.

Studies of distribution and recurrence of Helicobacter spp. gastric mucosa of dogs after triple therapy

PURPOSE: To analyze the triple antimicrobial therapy in positive Helicobacter spp. dogs and to investigate recurrence. METHODS: A total of 20 dogs underwent endoscopy followed by gastric biopsy using the rapid urease test and histopathology stained with Giemsa. Ten animals were treated with triple therapy recommended for humans and divided into control and experimental group. The control group was kept in isolation while the experimental group was placed in contact with positive animals during 60 days. RESULTS: The prevalence of infection in animals in this experiment was 100%, and more frequent in the fundus and the gastric body. Therapy for 7 days using clarithromycin, amoxicillin and lansoprazole was effective in 100% of the animals. Recurrence of the infection in 80% of dogs in the experimental group, while the control group remained eradicated after 60 days. CONCLUSION: Crowded environments associated with close contact with dogs infected with helicobacter are a determinant for transmission of Helicobacter spp. between canines.

Fluorescence In Situ Hybridization Confirms Clearance of VisibleHelicobacterspp. Associated with Gastritis in Dogs and Cats

The results of studies examining the role of Helicobacter spp. in the pathogenesis of canine and feline gastritis are inconclusive. Furthermore, data evaluating the effectiveness of medical therapy for eradication of Helicobacter infection are limited. To detect Helicobacter spp. in mucosal biopsies of dogs and cats diagnosed with gastritis, with fluorescence in situ hybridization (FISH). Three dogs and 2 cats with signs of chronic gastrointestinal disease. Dogs and cats infected with Helicobacter spp. were treated with triple antimicrobial therapy and fed an elimination diet for 21 days. Helicobacter spp. status in endoscopic (3 dogs, 1 cat) or surgical biopsies (1 cat) of gastric mucosa was compared pre- and posttreatment in each animal by histology, FISH analysis, and polymerase chain reaction (PCR). Gastritis of varying severity with intraglandular spiral bacteria was observed in all animals. Pretreatment diagnostic tests confirmed the presence of mucosal Helicobacter spp. in all animals by FISH and histopathology and in 4/5 animals by PCR. Rapid resolution of vomiting episodes was observed in all animals. Gastric biopsies performed after triple therapy revealed clearance of visible Helicobacter spp. by histopathology and negative FISH analysis, as well as PCR in all animals. Application of FISH to routine biopsy specimens enabled rapid and specific identification of Helicobacter spp. within the gastric mucosa of dogs and cats. Although medical therapy was useful in resolution of clinical signs and clearance of visible Helicobacter spp. in gastric biopsies, gastric inflammation persisted.

Therapeutic options for human brucellosis

Worldwide, human brucellosis is the most common zoonotic disease and it has gained increasing interest because of the potential use of Brucella as a biological weapon. Monotherapy for brucellosis is associated with a high relapse rate and dual therapy in different combinations is more efficacious. The combination regimen of intramuscular streptomycin with an oral tetracycline resulted in fewer relapses than the doxycycline–rifampin combination in meta-analysis and prospective studies, although the use of doxycycline and rifampin is a reasonable choice in certain conditions. Longer duration and triple antimicrobial therapy appear to improve outcome and prevent relapses, especially in patients with focal disease. Recently, the use of gentamicin-loaded microparticles and the use of new antibiotics, such as tigecycline, may hold future promise. In addition, there are a few studies of the enhanced effect of immune response stimulators, such as levimasole and IFN-2, in the treatment of brucellosis. The development of an effective subcellular Brucella vaccine would be an important step forward to curtail the disease. However, currently and for the near future, only the control of animal disease is possible using vaccine strategies.

Triple Antimicrobial Therapy and Acid Suppression in Dogs with Chronic Vomiting and GastricHelicobacterspp

Background:Helicobacter pyloriis a common cause of gastritis and peptic ulcers in humans. Many dogs, including those with gastritis and chronic vomiting, are infected withHelicobacterspp.Hypothesis: Triple antimicrobial therapy will eradicateHelicobacterinfection, improve gastritis, and reduce clinical signs. The addition of acid suppression medication will not improve results.Animals: Twenty‐four pet dogs with chronic vomiting and gastricHelicobacterspp.Methods: Dogs were randomly assigned to triple antimicrobial therapy with or without famotidine. Gastroduodenoscopy was performed 4 weeks and 6 months after therapy.Helicobacterspp status was determined by histologic assessment of gastric mucosal biopsy specimens.Results: Eradication rates for each treatment were not significantly different and combined were 75 and 42.9% at 4 weeks and 6 months, respectively. A greater improvement in gastritis scores occurred in dogs that becameHelicobacterspp negative. Overall, the frequency of vomiting was reduced by 86.4%, but there were no differences between treatments.Conclusions and Clinical Importance: Eradication rates ofHelicobacterspp with both treatments were not significantly different. Eradication rates at 6 months were modest, and more effective treatments should be developed. Acid suppression is not a necessary component of treatment protocols for dogs. Eradication of gastricHelicobacterspp was associated with improvement in gastritis scores. Dramatic reduction of the vomiting frequency occurred with both treatment protocols. GastricHelicobacterspp may cause or contribute to chronic vomiting and gastritis in some dogs.

Triple Antimicrobial Therapy and Acid Suppression in Dogs with Chronic Vomiting and Gastric Helicobacter spp

Helicobacter pylori is a common cause of gastritis and peptic ulcers in humans. Many dogs, including those with gastritis and chronic vomiting, are infected with Helicobacter spp. Triple antimicrobial therapy will eradicate Helicobacter infection, improve gastritis, and reduce clinical signs. The addition of acid suppression medication will not improve results. Twenty-four pet dogs with chronic vomiting and gastric Helicobacter spp. Dogs were randomly assigned to triple antimicrobial therapy with or without famotidine. Gastroduodenoscopy was performed 4 weeks and 6 months after therapy. Helicobacter spp status was determined by histologic assessment of gastric mucosal biopsy specimens. Eradication rates for each treatment were not significantly different and combined were 75 and 42.9% at 4 weeks and 6 months, respectively. A greater improvement in gastritis scores occurred in dogs that became Helicobacter spp negative. Overall, the frequency of vomiting was reduced by 86.4%, but there were no differences between treatments. Eradication rates of Helicobacter spp with both treatments were not significantly different. Eradication rates at 6 months were modest, and more effective treatments should be developed. Acid suppression is not a necessary component of treatment protocols for dogs. Eradication of gastric Helicobacter spp was associated with improvement in gastritis scores. Dramatic reduction of the vomiting frequency occurred with both treatment protocols. Gastric Helicobacter spp may cause or contribute to chronic vomiting and gastritis in some dogs.

Fournier’s gangrene: Report of thirty‐three cases and a review of the literature

Fournier's gangrene (FG) is an extensive fulminant infection of the genitals, perineum or the abdominal wall. The aim of this study is to share our experience with the management of this difficult infectious disease. Thirty-three male patients were admitted to our clinic with the diagnosis of FG between February 1988 and December 2003. The patient's age, etiology and predisposing factors, microbiological findings, duration of hospital stay, treatment, and outcome were analyzed. The patients were divided into two groups. The first 21 patients (Group I) were treated with broad-spectrum triple antimicrobial therapy, broad debridement, exhaustive cleaning, and then they underwent split-thickness skin grafts or delayed closure as needed. The other 12 patients (Group II) were treated with unprocessed honey (20-50 mL daily) and broad-spectrum triple antimicrobial therapy without debridement. Their wounds were cleaned with saline and then dressed with topical unprocessed honey. The wounds were inspected daily and the honey was reapplied after cleaning with normal saline. Then, the patients' scrotum and penis were covered with their own new scrotal skin. The mean age of the patients was 53.9 +/- 9.56 years (range = 23-71). The source of the gangrene was urinary in 23 patients, cutaneous in seven patients, and perirectal in three patients. The predisposing factors included diabetes mellitus for 11 patients, alcoholism for 10 patients, malnutrition for nine patients, and medical immunosuppression (chemotherapy, steroids, malignancy) for three patients. The mean duration of hospital stay was 41 +/- 10.459 (range = 14-54) days. Two patients in Group I died from severe sepsis. The clinical and cosmetic results were better in Group II than Group I. Necrotizing fasciitis of the perineum and genitalia is a severe condition with a high morbidity and mortality. Traditionally, good management is based on aggressive debridement, broad-spectrum antibiotics, and intensive supportive care but unprocessed honey might revolutionize the treatment of this dreadful disease by reducing its cost, morbidity, and mortality.

Needle Aspiration and Syndromic Management of Bartholin'S Abscess

A series of Bartholin's abscesses was managed on an outpatient basis by needle aspiration followed by triple antimicrobial therapy. The absence of Neisseria gonorrhoea was evident in 27.8 per cent of the cases. Based on the premise that Bartholin's abscess is to be treated as a sexually transmitted disease (STD), the choice of antimicrobials was made in line with the syndromic management of STDs. All the patients were reviewed after one week and two-thirds of them after six months. There was no long-term recurrence among the women who returned for follow-up. Client satisfaction was excellent. The procedure provides immediate relief, avoids hospitalisation and related costs, as well as the morbidity resulting from traditional surgical approaches. (Afr J Reprod Health 1999; 3 [1]: 103 - 108) Key Words : Bartholin's abscess, needle aspiration, sexually transmitted disease, syndromic management

Fournier’s Gangrene: Risk Assessment and Enzymatic Debridement with Lyophilized Collagenase Application

Objectives: Fournier’s gangrene (FG) is an abrupt, rapidly progressive, gangrenous infection of the external genitalia, perineum or abdominal wall and is a real urologic emergency. In this study, the risk factors of FG and the effects of enzymatic debridements on wound healing were investigated. Patients and Methods: We reviewed the records of 34 patients with FG to investigate the possible correlation between clinical outcome and infection focus, patient age, number of types of bacteria cultured, delay until presentation, predisposing diseases or accompanying conditions such as diabetes, neurologic deficit, chronic alcoholism and renal failure. Broad-spectrum triple antimicrobial therapy, aggressive and frequent surgical debridement, and if necessary urinary and colonic diversions were performed to control the infection. The effects of enzymatic debridements with topical lyophilized collagenase applications on the wound healing after the control of active infection were evaluated. Results: The average age of the patients was 55 years. The sources of infections were urogenital in 12 (35.3%), anorectal in 10 (29.4%), dermal in 10 (29.4%) and undetermined in 2 (5.8%) of the patients. The average presentation time was 4.4 days and the number of isolated bacteria was 3.05 per case. The number of isolated bacteria and surgical debridements, the duration of hospital stay and the rate of mortality in patients with anorectal foci were higher than those of the patients with urogenital or dermal foci (p < 0.05). Diabetes, uremia and advanced age did not significantly affect the number of surgical debridements, the duration of hospital stay and control of active infection. Mortality was increased in chronic alcoholism, a finding of undetermined significance. Enzymatic debridements decreased the duration of hospital stay (p < 0.05). Five patients (14.7%) died despite prompt medical and surgical preventive measures. Conclusion: Chronic alcoholism, anorectal infection foci, neurological deficit and delayed presentation were found as risk factors in FG. Diabetes and advanced age did not affect the progression of disease in our cases. Enzymatic debridements decrease the number of surgical debridements and the duration of hospital stay.

The relationship between helicobacter infection and peptic ulcer disease

Helicobacter pylori infection of gastric mucosa is widespread, causing asymptomatic superficial gastritis; however, symptomatic disease in the form of duodenal and gastric ulcers is present only in a small proportion of infected individuals. H pylori causes most of the peptic ulcer disease that is not associated with nonsteroidal anti-inflammatory drug use or gastrinoma. The best evidence for H pylori causing peptic ulcer disease is the reduction of recurrence of this disease with eradication of the organism. The pathogenesis of peptic ulcer disease from initial H pylori infection is not yet completely understood. Diagnosis of H pylori infection in peptic ulcer disease can be made with invasive (endoscopic) and noninvasive (serologic or breath test) testing. Treatment for patients with peptic ulcers due to H pylori is recommended after the diagnosis is established. Triple antimicrobial therapy for two weeks is the best investigated regimen, but two drug therapies that combine a proton pump inhibitor and an antibiotic or antibiotics are available as alternatives.

Is the sanctuary where Helicobacter pylori avoids antibacterial treatment intracellular?

The sanctuary site where Helicobacter pylori evades antimicrobial therapy is unknown, but considerable data exist about an intracellular location for H pylori. Ten H pylori-infected volunteers received standard triple antimicrobial therapy for 2 weeks. Gastric mucosal biopsy specimens were obtained with jumbo forceps on therapy days 0, 3, 14, and 42. Hematoxylin-eosin staining was used for classification of gastritis and the Genta stain for the visualization of H pylori. Immunohistochemical staining was used to detect HLA-DR antigens, human heat shock protein (HSP60), and the bacterial HSP60 antigen. Bacterial HSP60 was expressed on the mucosal surface and within epithelial cells. No such expression of human HSP60 was found, which supports a bacterial origin for the intracellular HSP60. Coexpression of bacterial HSP60 and HLA-DR was always observed, indicating an ongoing local immune response. Infection was cleared on day 14, but when examined 4 weeks after completion of therapy, Genta staining indicated that only five volunteers remained free of H pylori. However, results of immunohistochemical staining were negative at this time for only two volunteers. Disappearance of intracellular expression of bacterial HSP60 remained after therapy and correlated with the intensity of chronic inflammatory cell infiltration. These data are consistent with the intracellular localization of H pylori having a role in inflammation and as a protective strategy against extracellular antibacterial activity.

Use of PCR and culture to detect Helicobacter pylori in naturally infected cats following triple antimicrobial therapy.

Helicobacter pylori causes gastritis and peptic ulcers and is linked to gastric cancer. Domestic cats from a commercial source were found to be naturally infected with H. pylori, and studies were undertaken to eradicate H. pylori from infected cats by using triple antimicrobial therapy. Eight cats infected with H. pylori were used in the study. Six cats received a 21-day course of oral amoxicillin, metronidazole, and omeprazole, and two cats served as controls. Two weeks and 4 weeks posttreatment (p.t.), all six treated cats were negative at several sites (saliva, gastric juice, and gastric mucosa) for H. pylori by culture. However, as determined by PCR with primers specific for the 26-kDa product, the majority of cats at 2 and 4 weeks p.t. had gastric fluid samples which were positive for H. pylori and three of three cats at 2 weeks p.t. had dental plaque which was positive for H. pylori. At 6 weeks p.t., all six cats had H. pylori-negative cultures for samples from several gastric sites taken at necropsy, and only one cat had H. pylori cultured from gastric juice. PCR analysis revealed that five of six cats had H. pylori DNA amplification products from plaque, saliva, and/or gastric fluid samples. Negative bacterial cultures for cats for which there was demonstrable PCR amplification of H. pylori DNA may reflect the inability of in vitro culture techniques to isolate small numbers of H. pylori organisms, focal colonization at sites not cultured, or a failure of the antibiotics to successfully eradicate H. pylori from extragastric sites which allowed subsequent recolonization of the stomach after cessation of therapy. Alternatively, the treatment strategy may have induced in vivo viable but nonculturable coccoid forms of H. pylori. The H. pylori cat model should allow further studies to test these hypotheses as well as the efficacies of other combined therapeutic regimens. Also, because 100% of these cats were naturally infected with H.pylori, this model should prove useful in exploring mechanisms whereby human populations in underdeveloped countries, which have H. pylori infection rates approaching 100%, have a high rate of recurrence of H. pylori infection after use of prescribed antibiotic therapies that successfully eradicate H. pylori in individuals in developed countries.