trimethoprim--sulfamethoxazole-drug-combination and Inflammation

Undernutrition in childhood is estimated to cause 3.1 million child deaths annually through a potentiating effect on common infectious diseases, such as pneumonia and diarrhea. In turn, overt and subclinical infections, and inflammation, especially in the gut, alter nutrient intake, absorption, secretion, diversion, catabolism, and expenditure.. A narrative overview of the current understanding of infections, inflammation, and antimicrobials in relation to childhood malnutrition.. Searches for pivotal papers were conducted using PUBMED 1966-January 2013; hand searches of the references of retrieved literature; discussions with experts; and personal experience from the field.. Although the epidemiological evidence for increased susceptibility to life-threatening infections associated with malnutrition is strong, we are only just beginning to understand some of the mechanisms involved. Nutritional status and growth are strongly influenced by environmental enteric dysfunction (EED), which is common among children in developing countries, and by alterations in the gut microbiome. As yet, there are no proven interventions against EED. Antibiotics have long been used as growth promoters in animals. Trials of antibiotics have shown striking efficacy on mortality and on growth in children with uncomplicated severe acute malnutrition (SAM) or HIV infection. Antibiotics act directly by preventing infections and may act indirectly by reducing subclinical infections and inflammation. We describe an ongoing multicenter, randomized, placebo-controlled trial of daily cotrimoxazole prophylaxis to prevent death in children recovering from complicated SAM. Secondary outcomes include growth, frequency and etiology of infections, immune activation and function, the gut microbiome, and antimicrobial resistance. The trial is expected to be reported in mid-2014.. As well as improving nutritional intake, new case management strategies need to address infection, inflammation, and microbiota and assess health outcomes rather than only anthropometry.

Topics: Animals; Anti-Infective Agents; Child, Preschool; Humans; Infant; Infection Control; Infections; Inflammation; Intestines; Kenya; Malnutrition; Microbiota; Nutritional Status; Randomized Controlled Trials as Topic; Trimethoprim, Sulfamethoxazole Drug Combination

Cotrimoxazole preventive therapy (CPT) in human immunodeficiency virus (HIV) infection is a World Health Organization-recommended standard of care in resource-limited settings, but the mechanism of CPT's beneficial effects is unclear. The COSTOP trial (ISRCTN44723643) evaluated the noninferiority of discontinuing CPT in stabilized patients on antiretroviral therapy. The COSTOP immunology substudy was conducted on a subset of COSTOP participants randomized to continue CPT (n = 86) or discontinue CPT (placebo, n = 86) as daily treatment for 1 year.. We evaluated whether CPT reduces microbial translocation, indicated by the presence of bacterial lipopolysaccharide (LPS) and LPS control factors such as soluble CD14 (sCD14) and endotoxin core antibody (EndoCAb immunoglobulin M [IgM]) in plasma. Intestinal barrier damage as indicated by plasma intestinal fatty acid binding protein (IFABP), T-cell activation, and the inflammatory markers C-reactive protein (CRP), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α) were also evaluated.. We found no significant change in markers of microbial translocation (LPS, IFABP, sCD14, and T-cell activation), with decreased EndoCAb IgM. There was significant increase in inflammation markers (CRP and IL-6) after stopping CPT compared to those who continued CPT.. These results add to the evidence of immunological benefits of CPT among HIV-infected populations in resource-limited settings. However, no evidence of reducing microbial translocation was observed.

Topics: Adult; Anti-HIV Agents; Biomarkers; C-Reactive Protein; CD4 Lymphocyte Count; Double-Blind Method; Female; HIV Infections; Humans; Immunoglobulin M; Inflammation; Interleukin-6; Linear Models; Male; Middle Aged; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda; Withholding Treatment

Long-term cotrimoxazole prophylaxis reduces mortality and morbidity in HIV infection, but the mechanisms underlying these clinical benefits are unclear. Here, we investigate the impact of cotrimoxazole on systemic inflammation, an independent driver of HIV mortality. In HIV-positive Ugandan and Zimbabwean children receiving antiretroviral therapy, we show that plasma inflammatory markers were lower after randomization to continue (

Topics: CD4-Positive T-Lymphocytes; Child; Child, Preschool; Cytokines; Disease Progression; Epithelial Cells; Gastrointestinal Microbiome; HIV Infections; Humans; Inflammation; Inflammation Mediators; Intestines; Nutritional Status; Phenotype; Streptococcus; Trimethoprim, Sulfamethoxazole Drug Combination

Women living with HIV (WLHIV) have an increased risk of malaria in pregnancy (MiP). It is unclear if MiP in WLHIV causes a systemic inflammatory response and increases the risk of adverse birth outcomes, especially for women receiving antiretroviral therapy (ART) and daily trimethoprim-sulfamethoxazole (TMP/SXT). We analyzed repeated plasma samples in a cohort of malaria-exposed Ugandan WLHIV receiving ART and daily TMP/SXT to examine changes in inflammatory markers across pregnancy and their association with birth outcomes. Concentrations of CHI3L1, CRP, IL-18BP, IL-6, sICAM-1, and sTNFR2 were quantified by ELISA in 1115 plasma samples collected over pregnancy from 326 women. MiP was associated with increased sTNFR2, sICAM-1 and IL-18BP concentrations across pregnancy. Women who delivered preterm had elevated concentrations of sTNFR2 and altered levels of IL-6 during pregnancy. Women with sTNFR2 concentrations in the highest quartile within 6 weeks of delivery had an increased relative risk of preterm birth. Our results indicate that despite daily TMP/SXT, MiP in WLHIV induced a systemic inflammatory response that was associated with an increased risk of preterm birth. These findings highlight the need for additional strategies to protect WLHIV from malaria infection in pregnancy to promote healthy outcomes for mother and child.

Topics: Adult; Anti-Retroviral Agents; Cohort Studies; Female; HIV; HIV Infections; Humans; Incidence; Infant, Newborn; Inflammation; Malaria; Pregnancy; Premature Birth; Prognosis; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda

Macrolide antibiotics are frequently prescribed to patients with symptoms of a common cold. Despite their lack of proven antiviral activity, macrolide antibiotics may have anti-inflammatory actions, such as inhibition of mucus secretion and production of interleukins 6 and 8 by epithelial cells. Because the symptoms of rhinovirus colds are attributed to the inflammatory response to infection, we studied the effects of treatment with clarithromycin on the symptomatic and inflammatory response to nasal inoculation with rhinovirus.. We performed a prospective, double-blind, controlled trial in 24 healthy subjects who were seronegative for antibodies to rhinovirus-16. Subjects were randomly assigned to receive either clarithromycin (500 mg) or trimethoprim-sulfamethoxazole (800/160 mg, as a control antibiotic) twice a day for 8 days, beginning 24 hours before inoculation with rhinovirus-16.. All 12 subjects in each group were infected and developed symptomatic colds. The groups did not differ in the intensity of cold symptoms (median [25th to 75th percentile] score in the clarithromycin group of 25 [5 to 33] versus 21 [11 to 26] in the trimethoprim-sulfamethoxazole group, P = 0.86), weight of nasal secretions (25 g [8 to 56 g] versus 12 g [5 to 28 g], P = 0.27), or decline in nasal peak flow during the 8 days following viral inoculation. In both groups, similar and significant increases from baseline were observed in the numbers of total cells and neutrophils, and in the concentrations of interleukins 6 and 8, in nasal lavage fluid during the cold. The changes that we observed did not differ from those in an untreated historical control group.. We conclude that clarithromycin treatment has little or no effect on the severity of cold symptoms or the intensity of neutrophilic nasal inflammation in experimental rhinovirus-16 colds.

Topics: Adult; Anti-Bacterial Agents; Anti-Infective Agents; Clarithromycin; Common Cold; Double-Blind Method; Female; Humans; Inflammation; Interleukin-6; Interleukin-8; Leukocyte Count; Male; Nasal Lavage Fluid; Neutrophils; Prospective Studies; Rhinovirus; Severity of Illness Index; Trimethoprim, Sulfamethoxazole Drug Combination

We performed a prospective multicentre study to evaluate the efficacy of therapeutic strategies currently used for ocular toxoplasmosis in a large number of patients (n = 106). Treatment was given for at least four weeks and consisted of three triple drug combinations: group 1, pyrimethamine, sulphadiazine and corticosteroids (n = 29); group 2. clindamycin, sulphadiazine and corticosteroids (n = 37); and group 3. cotrimoxazole (trimethoprim and sulphamethoxazole) and corticosteroids (n = 8). Patients with peripheral retinal lesions remained without systemic therapy (group 4, n = 32). Patients from group 1 received leucovorin 5 mg twice a week. No difference in the duration of inflammatory activity was observed between the treated and untreated patients or between the separate groups of patients. The most important factor predicting the duration of inflammatory activity was the size of the retinal focus itself, independently of the therapy given (P less than 0.05). We showed a reduction in size of the retinal inflammatory focus in 52% of the pyrimethamine patients as compared to 25% of untreated cases. However the most frequent side effects were also associated with pyrimethamine medication and included hematologic complications as thrombocytopenia and leucopenia despite leucovorin medication.

Topics: Chorioretinitis; Clindamycin; Coccidiostats; Drug Therapy, Combination; Humans; Inflammation; Multicenter Studies as Topic; Prospective Studies; Pyrimethamine; Retina; Toxoplasmosis, Ocular; Trimethoprim, Sulfamethoxazole Drug Combination

Toxoplasma gondii is a worldwide prevalent parasite. The infection has been linked to variable inflammatory effects including neuroinflammation. Biochanin A (BCA) is an isoflavone, known for its anti-inflammatory and anti-oxidative properties. In this study, we examined the effect of BCA on the brain and liver inflammatory lesions in a murine model with chronic toxoplasmosis. Mice were divided in to six groups: non-infected control, non-infected BCA-treated, and four infected groups with Toxoplasma gondii Me49-type II cystogenic strain: infected control, BCA (50 mg/kg/day)-treated, combined BCA/cotrimoxazole-treated and cotrimoxazole (370 mg/kg/day) alone-treated. Gene expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and inducible nitric oxide synthase (iNOS) was evaluated by quantitative real-time PCR in the brain and liver tissues. In the infected control group, an upregulation of TNF-α and IL-1β mRNA expression levels was found. However, a downregulation of iNOS expression was detected in the brain of infected control mice. In both BCA- and combined-treated groups, the brain and liver tissues showed significantly reduced inflammatory lesions compared to the infected control mice with inhibited TNF-α and IL-1β mRNA levels. The iNOS expression levels in the brain tissues of BCA group were significantly higher than the levels of the infected control group. BCA alone or combined significantly reduced T. gondii cyst count in the brain tissues. In conclusion, the anti-inflammatory activity of BCA was demonstrated in the brain tissues of mice with chronic toxoplasmosis with decreased TNF-α and IL-1β expression levels and increased iNOS expression levels.

Topics: Animals; Genistein; Inflammation; Isoflavones; Mice; RNA, Messenger; Toxoplasma; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination; Tumor Necrosis Factor-alpha

Antimicrobials have become a mainstay of healthcare in the past century due to their activity against pathogens. More recently, it has become clear that they can also affect health via their impact on the microbiota and inflammation. This may explain some of their clinical benefits despite global increases in antimicrobial resistance (AMR) and reduced antimicrobial effectiveness. We showed in a randomized controlled trial of stopping versus continuing cotrimoxazole prophylaxis among HIV-positive Zimbabwean children taking antiretroviral therapy (ART), that continuation of cotrimoxazole persistently suppressed gut-resident viridans group streptococcal species (VGS) that were associated with intestinal inflammation. In this addendum, we provide a broader overview of how antibiotics can shape the microbiota and use high read-depth whole metagenome sequencing data from our published study to investigate whether (i) the impact of cotrimoxazole on gut VGS and (ii) VGS associated inflammation, is attributable to strain-level variability. We focus on

Topics: Anti-Bacterial Agents; Anti-HIV Agents; Antibiotic Prophylaxis; Child; Feces; Gastrointestinal Microbiome; HIV Infections; Humans; Inflammation; Intestines; Species Specificity; Streptococcus salivarius; Trimethoprim, Sulfamethoxazole Drug Combination; Viridans Streptococci; Zimbabwe

Nephrogenic adenoma is an uncommon urothelial lesion that has been associated with chronic inflammation and surgical manipulation of the urinary tract. Several cases of vesical nephrogenic adenoma in patients with a history of renal transplantation have been reported. The present case report reviewed the management of recurrent nephrogenic adenoma in a 6-year-old boy with history of renal transplantation 3 years before the diagnosis of nephrogenic adenoma. After multiple surgical resections for recurrent nephrogenic adenoma, the lesion finally resolved with long-term treatment with ibuprofen (Motrin) and trimethoprim and sulfamethoxazole (Septra).

Topics: Adenoma; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Biopsy; Child; Endoscopy; Humans; Ibuprofen; Inflammation; Kidney Transplantation; Male; Recurrence; Renal Insufficiency; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Bladder Neoplasms

Topics: Abdominal Cavity; Aged, 80 and over; Anti-Infective Agents; Ascites; Cefotaxime; Diagnosis, Differential; Diet, Sodium-Restricted; Diuretics; Edema; Humans; Inflammation; Liver Cirrhosis; Lower Extremity; Male; Norfloxacin; Paracentesis; Peritonitis; Spironolactone; Tomography, X-Ray Computed; Trimethoprim, Sulfamethoxazole Drug Combination; Ultrasonography

The T cell-mediated immune response elicited by Pneumocystis plays a key role in pulmonary damage and dysfunction during Pneumocystis carinii pneumonia (PcP). Mice depleted of CD4(+) and CD8(+) T cells prior to infection are markedly protected from PcP-related respiratory deficit and death, despite progressive lung infection. However, the therapeutic effectiveness of Ab-mediated disruption of T cell function in mice already displaying clinical symptoms of disease has not been determined. Therefore, a murine model of PcP-related immune reconstitution inflammatory syndrome was used to assess whether Ab to the pan-T cell molecule CD3 is effective for reducing the severity of PcP when administered after the onset of disease. Mice that received anti-CD3 Ab exhibited a rapid and dramatic halt in the PcP-associated pulmonary function decline within 1 week after treatment, and a striking enhancement of survival rate compared with mice receiving the control Ab. Physiologic improvement in anti-CD3 treated mice was associated with a significant reduction in the number of CD4(+) and CD8(+) T cells recovered in lung lavage fluid. This effectiveness of anti-CD3 was noted whether the mice also received antibiotic therapy with trimethoprim-sulfamethoxazole. These data suggest that monoclonal Ab-mediated disruption of T cell function may represent a specific and effective adjunctive therapy to rapidly reverse the ongoing pathologic immune response occurring during active PcP. Thus, the anti-human CD3 monoclonal Ab OKT3, which is already in clinical use, has the potential to be developed as an adjunctive therapy for PcP.

Topics: Animals; Anti-Infective Agents; Antibodies; Bronchoalveolar Lavage Fluid; CD3 Complex; Disease Models, Animal; Inflammation; Lymphocyte Depletion; Mice; Pneumonia, Pneumocystis; Reverse Transcriptase Polymerase Chain Reaction; Trimethoprim, Sulfamethoxazole Drug Combination

The case of Mr M, a previously healthy 39-year-old man with erythema and swelling of his finger, illustrates the issues involved in treating community-acquired skin and soft tissue infections since the emergence of methicillin-resistant Staphylococcus aureus (MRSA) in the community. Most community-acquired infections of the skin and soft tissues are caused by S aureus or Streptococcus pyogenes. Until recently, infections due to such organisms in the United States could safely be treated with an oral antistaphylococcal penicillin or an oral first-generation cephalosporin. However, the emergence of methicillin-resistant staphylococci as community-acquired pathogens has changed the picture as far as empirical therapy is concerned. Not only do community-acquired MRSA bacteria cause furunculitis and cellulitis, they have also been involved in a variety of more serious and life-threatening infections. Most of these organisms are susceptible to trimethoprim-sulfamethoxazole, minocycline, doxycycline, and rifampin, and these agents, along with clindamycin, have been used in the therapy of such infections, even though no clinical trials have proven their efficacy. For more serious, life-threatening infections, linezolid or parenteral agents such as vancomycin or daptomycin should be considered.

Topics: Adult; Anti-Bacterial Agents; Cellulitis; Community-Acquired Infections; Drainage; Drug Resistance, Bacterial; Erythema; Humans; Inflammation; Infusions, Intravenous; Male; Methicillin Resistance; Penicillins; Recurrence; Risk Factors; Skin Diseases, Bacterial; Staphylococcal Skin Infections; Staphylococcus aureus; Trimethoprim, Sulfamethoxazole Drug Combination

To determine whether treatment with an antibiotic (trimethoprim-sulfamethoxazole) reduced the inflammatory response in a murine form of Streptococcus pneumoniae-induced rhinosinusitis.. We randomized 18 C57BL/6 mice to either treatment with intraperitoneal trimethoprim-sulfamethoxazole (Bactrim, 30 mg/kg) or no treatment (control). After 2 days, we inoculated all C57BL/6 mice intranasally with a Bactrim-susceptible strain of Streptococcus pneumoniae, ATCC 49619, suspended in Trypticase soy broth. At day 5 after bacterial inoculation, we sacrificed the mice and prepared histopathologic sections of their sinuses after culturing their nasal cavities by lavage.. Animal care facility at a tertiary, academic institution.. The histopathologic sections of the sinuses were examined in a blind manner for the percent of sinus cavity area occupied by neutrophil clusters, and for the number of neutrophils per square millimeter of sinus mucosa.. The Bactrim group had a significantly smaller sinus area occupied by neutrophil clusters (1.58% +/- 1.13 vs 4.38% +/- 3.41; P < 0.05), significantly fewer neutrophils infiltrating the mucosa (58.81 +/- 29.63/mm2 vs 105.85 +/- 48.49/mm2; P < 0.05), and significantly less growth of Streptococcus pneumoniae colonies in the intranasal cultures (8 few and 1 moderate vs 3 few, 3 moderate, and 1 many; P = 0.05) compared to the control group.. In our murine model of acute rhinosinusitis, Bactrim decreased the number of neutrophil clusters in the sinus cavities, the number of neutrophils infiltrating the sinus mucosa, and the growth of Streptococcus pneumoniae. We propose that our murine model can be used for the study of the pathophysiology and treatment of acute rhinosinusitis.

Topics: Animals; Disease Models, Animal; Inflammation; Leukocyte Count; Mice; Neutrophils; Rhinitis; Sinusitis; Streptococcal Infections; Streptococcus pneumoniae; Trimethoprim, Sulfamethoxazole Drug Combination