zithromax and Sepsis

To describe a case of severe sepsis, cavitary pneumonia, and pyomyositis caused by Arcanobacterium haemolyticum.. An 18-year-old male with a medical history significant for mild asthma presented to the emergency department complaining of a 7-day history of fever, diffuse myalgias, nausea, vomiting, diarrhea, and pain in his right upper quadrant, right shoulder, and left thigh. Cultures of blood, bronchoalveolar fluid, and surface and surgical swabs from the patient's left lower extremity grew A. haemolyticum. The patient was successfully treated with intravenous penicillin G 4 million units every 4 hours and azithromycin 500 mg once daily for 14 days. Within 36 hours after initiation of focused therapy, he became afebrile, pain decreased, and pulmonary symptoms abated. Oral azithromycin 500 mg/day for an additional 3 weeks was prescribed on discharge, and the patient showed no relapse at 2-month follow-up.. A. haemolyticum is a weakly acid-fast, branching gram-positive bacillus most commonly implicated in pharyngitis in healthy adolescents and skin and soft-tissue infections in older, immunocompromised patients. Systemic infections are rarely reported in the literature. This organism remains susceptible to most classes of antimicrobials, including penicillins, cephalosporins, carbapenems, macrolides, tetracyclines, clindamycin, and vancomycin. Routine resistance has been reported only with trimethoprim/sulfamethoxazole.. To our knowledge, there are no published case reports of severe sepsis caused by A. haemolyticum. While treatment options are numerous, we recommend the use of intravenous penicillin or a cephalosporin as first-line pharmacologic management of deep-seated infections caused by this rare organism.

Topics: Actinomycetales Infections; Adolescent; Anti-Bacterial Agents; Arcanobacterium; Azithromycin; Humans; Male; Penicillins; Pneumonia, Bacterial; Pyomyositis; Sepsis

The use of azithromycin reduces maternal infection in women during unplanned cesarean delivery, but its effect on those with planned vaginal delivery is unknown. Data are needed on whether an intrapartum oral dose of azithromycin would reduce maternal and offspring sepsis or death.. In this multicountry, placebo-controlled, randomized trial, we assigned women who were in labor at 28 weeks' gestation or more and who were planning a vaginal delivery to receive a single 2-g oral dose of azithromycin or placebo. The two primary outcomes were a composite of maternal sepsis or death and a composite of stillbirth or neonatal death or sepsis. During an interim analysis, the data and safety monitoring committee recommended stopping the trial for maternal benefit.. A total of 29,278 women underwent randomization. The incidence of maternal sepsis or death was lower in the azithromycin group than in the placebo group (1.6% vs. 2.4%), with a relative risk of 0.67 (95% confidence interval [CI], 0.56 to 0.79; P<0.001), but the incidence of stillbirth or neonatal death or sepsis was similar (10.5% vs. 10.3%), with a relative risk of 1.02 (95% CI, 0.95 to 1.09; P = 0.56). The difference in the maternal primary outcome appeared to be driven mainly by the incidence of sepsis (1.5% in the azithromycin group and 2.3% in the placebo group), with a relative risk of 0.65 (95% CI, 0.55 to 0.77); the incidence of death from any cause was 0.1% in the two groups (relative risk, 1.23; 95% CI, 0.51 to 2.97). Neonatal sepsis occurred in 9.8% and 9.6% of the infants, respectively (relative risk, 1.03; 95% CI, 0.96 to 1.10). The incidence of stillbirth was 0.4% in the two groups (relative risk, 1.06; 95% CI, 0.74 to 1.53); neonatal death within 4 weeks after birth occurred in 1.5% in both groups (relative risk, 1.03; 95% CI, 0.86 to 1.24). Azithromycin was not associated with a higher incidence in adverse events.. Among women planning a vaginal delivery, a single oral dose of azithromycin resulted in a significantly lower risk of maternal sepsis or death than placebo but had little effect on newborn sepsis or death. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; A-PLUS ClinicalTrials.gov number, NCT03871491.).

Topics: Administration, Oral; Anti-Bacterial Agents; Azithromycin; Delivery, Obstetric; Female; Humans; Infant, Newborn; Neonatal Sepsis; Perinatal Death; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Outcome; Sepsis; Stillbirth; United States

Maternal and neonatal infections are among the most frequent causes of maternal and neonatal mortality, and current antibiotic strategies have been ineffective in preventing many of these deaths. A randomised clinical trial conducted in a single site in The Gambia showed that treatment with an oral dose of 2 g azithromycin versus placebo for all women in labour reduced certain maternal and neonatal infections. However, it is unknown if this therapy reduces maternal and neonatal sepsis and mortality. In a large, multinational randomised trial, we will evaluate the impact of azithromycin given in labour to improve maternal and newborn outcomes.. This randomised, placebo-controlled, multicentre clinical trial includes two primary hypotheses, one maternal and one neonatal. The maternal hypothesis is to test whether a single, prophylactic intrapartum oral dose of 2 g azithromycin given to women in labour will reduce maternal death or sepsis. The neonatal hypothesis will test whether this intervention will reduce intrapartum/neonatal death or sepsis. The intervention is a single, prophylactic intrapartum oral dose of 2 g azithromycin, compared with a single intrapartum oral dose of an identical appearing placebo. A total of 34 000 labouring women from 8 research sites in sub-Saharan Africa, South Asia and Latin America will be randomised with a one-to-one ratio to intervention/placebo. In addition, we will assess antimicrobial resistance in a sample of women and their newborns.. The study protocol has been reviewed and ethics approval obtained from all the relevant ethical review boards at each research site. The results will be disseminated via peer-reviewed journals and national and international scientific forums.. NCT03871491 (https://clinicaltrials.gov/ct2/show/NCT03871491?term=NCT03871491&draw=2&rank=1).

Topics: Azithromycin; Communicable Diseases; Developing Countries; Female; Humans; Infant, Newborn; Multicenter Studies as Topic; Perinatal Death; Randomized Controlled Trials as Topic; Sepsis

Sepsis is a leading cause of neonatal death. Intrapartum azithromycin reduces neonatal nasopharyngeal carriage of potentially pathogenic bacteria, a prerequisite for sepsis. Early antibiotic exposure has been associated with microbiota perturbations with varying effects. This study aims to understand the effect of intrapartum azithromycin intervention on the developing nasopharyngeal microbiota of the child.. Using 16S rRNA gene sequencing, we analysed the microbiota of 343 nasopharyngeal samples collected from birth to 12 months from 109 healthy infants selected from a double-blind randomized placebo-controlled clinical trial conducted in the Gambia (PregnAnZI-1). In the trial, 829 women were given 2g oral azithromycin or placebo (1:1) during labour with the objective of reducing bacterial carriage in mother and child during the neonatal period. The post-hoc analysis presented here assessed the effect of the intervention on the child nasopharyngeal microbiota development.. 55 children were from mothers given azithromycin and 54 from mothers given placebo. Comparing arms, we found an increase in alpha-diversity at day-6 (p = 0·018), and a significant effect on overall microbiota composition at days 6 and 28 (R. These results indicate that intrapartum azithromycin caused short-term alterations in the nasopharyngeal microbiota with modest overall effect at 12 months of age. Further exploration of the effects of these variations on microbiome function will give more insight on the potential risks and benefits, for the child, associated with this intervention.. This work was jointly funded by the Medical Research Council (UK) (MC_EX_MR/J010391/1/MRC), Bill & Melinda Gates Foundation (OPP1196513), and MRCG@LSHTM Doctoral Training Program.

Topics: Anti-Bacterial Agents; Azithromycin; Bacteria; Child; Double-Blind Method; Female; Humans; Infant; Infant, Newborn; Microbiota; RNA, Ribosomal, 16S; Sepsis

To compare the effectiveness of single-dose azithromycin, with or without amoxicillin, with placebo to prevent peripartum infection in laboring women.. We conducted a multicenter, three-group, double-blind randomized controlled trial of women with viable term nonanomalous pregnancies with either prolonged labor of 18 hours or longer or rupture of membranes for 8 hours or longer in Cameroon. Women with chorioamnionitis before randomization, study drug contraindications, or planned cesarean births were excluded. Women were randomized to oral azithromycin 1 g-placebo (group 1), oral azithromycin 1 g-oral amoxicillin 2 g (group 2), or placebo-placebo (group 3). All groups received usual care, including antibiotics given at the health care professional's discretion. The primary outcome was a composite of maternal peripartum infection or death from any cause up to 6 weeks postpartum. Two primary comparisons (group 1 vs group 3 and group 2 vs group 3) were planned. We estimated that 241 women per group (planning for 750 total) would provide 80% power at two-sided α=0.05 (0.025 per comparison) to detect a 50% effect size assuming 20% baseline composite infection rate.. From January 6, 2018, to May 15, 2020, 6,531 women were screened, and 756 (253 in group 1, 253 in group 2, and 250 in group 3) were randomized. Baseline characteristics (including body mass index, duration of rupture of membranes or labor, and parity) were balanced across groups, except for maternal age. More than 60% of women in each group received usual-care antibiotics: more than 90% penicillin and approximately 50% for prolonged rupture of membranes across all study groups. Composite outcome incidences were similar in antibiotic groups 1 (6%) and 2 (7%) compared with placebo group 3 (10%) (RR 0.6, 95% CI 0.3-1.2; 0.7, 95% CI 0.4-1.3, respectively). Chorioamnionitis and wound infection were significantly lower in group 2 (3.2% vs 0.4% and 4% vs 0.8% respectively, both P=.02) compared with group 3. There were no differences in other maternal or neonatal outcomes including neonatal infection.. A single dose of oral azithromycin with or without amoxicillin for prolonged labor or rupture of membranes at term did not reduce maternal peripartum or neonatal infection. Observed lower than expected infection rates and frequent usual-care antibiotic use may have contributed to these findings.. ClinicalTrials.gov, NCT03248297.. Merck for Mothers Investigator Studies Program grant.

Topics: Abscess; Administration, Oral; Adult; Amoxicillin; Anti-Bacterial Agents; Antibiotic Prophylaxis; Azithromycin; Bacterial Infections; Cameroon; Cesarean Section; Chorioamnionitis; Double-Blind Method; Endometritis; Female; Humans; Infant, Newborn; Infection Control; Labor, Obstetric; Peripartum Period; Pregnancy; Pregnancy Complications, Infectious; Sepsis; Treatment Outcome; Wound Infection

To explore whether the effect of azithromycin (AZI) on postcesarean infections varied by the presence/absence of genital mycoplasmataceae placental colonization.. This was a single-center substudy of multicenter double-blind C/SOAP (Cesarean Section Optimal Antibiotic Prophylaxis) trial of women randomized to AZI or placebo (+cefazolin) antibiotic prophylaxis at cesarean. Chorioamnion/placenta specimens were tested for genital mycoplasmataceae colonization by polymerase chain reaction. Primary outcome was a composite of endometritis, wound infection, or other infections up to 6 weeks postpartum. Analysis was intent-to-treat; logistic regression was used to evaluate interactions between treatment assignment (AZI/placebo) and the presence/absence of mycoplasmataceae and to quantify effects of AZI in analyses stratified by the presence/absence of these microorganisms.. The reduction in postcesarean infection with AZI does not vary based on the presence or absence of genital mycoplasmataceae placental colonization.

Topics: Adult; Anti-Bacterial Agents; Antibiotic Prophylaxis; Azithromycin; Cesarean Section; Endometritis; Female; Humans; Mycoplasma; Placenta; Pregnancy; Puerperal Infection; Sepsis; Surgical Wound Infection; Ureaplasma

The addition of azithromycin to standard regimens for antibiotic prophylaxis before cesarean delivery may further reduce the rate of postoperative infection. We evaluated the benefits and safety of azithromycin-based extended-spectrum prophylaxis in women undergoing nonelective cesarean section.. In this trial conducted at 14 centers in the United States, we studied 2013 women who had a singleton pregnancy with a gestation of 24 weeks or more and who were undergoing cesarean delivery during labor or after membrane rupture. We randomly assigned 1019 to receive 500 mg of intravenous azithromycin and 994 to receive placebo. All the women were also scheduled to receive standard antibiotic prophylaxis. The primary outcome was a composite of endometritis, wound infection, or other infection occurring within 6 weeks.. The primary outcome occurred in 62 women (6.1%) who received azithromycin and in 119 (12.0%) who received placebo (relative risk, 0.51; 95% confidence interval [CI], 0.38 to 0.68; P<0.001). There were significant differences between the azithromycin group and the placebo group in rates of endometritis (3.8% vs. 6.1%, P=0.02), wound infection (2.4% vs. 6.6%, P<0.001), and serious maternal adverse events (1.5% vs. 2.9%, P=0.03). There was no significant between-group difference in a secondary neonatal composite outcome that included neonatal death and serious neonatal complications (14.3% vs. 13.6%, P=0.63).. Among women undergoing nonelective cesarean delivery who were all receiving standard antibiotic prophylaxis, extended-spectrum prophylaxis with adjunctive azithromycin was more effective than placebo in reducing the risk of postoperative infection. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development; C/SOAP ClinicalTrials.gov number, NCT01235546 .).

Topics: Adult; Anti-Bacterial Agents; Antibiotic Prophylaxis; Azithromycin; Cesarean Section; Endometritis; Female; Humans; Infant, Newborn; Pregnancy; Puerperal Infection; Sepsis; Surgical Wound Infection; Survival Analysis; Young Adult

Topics: Anti-Bacterial Agents; Azithromycin; Female; Humans; Sepsis; Vagina

Topics: Anti-Bacterial Agents; Azithromycin; Female; Humans; Sepsis; Vagina

Topics: Anti-Bacterial Agents; Azithromycin; Female; Humans; Sepsis; Vagina

Topics: Anti-Bacterial Agents; Azithromycin; Female; Humans; Sepsis; Vagina

Typhoid fever, caused by Salmonella enterica serovar Typhi, is a common cause of febrile illness, especially in lower middle-income countries. The only known reservoirs of this infection are humans, and it is prevalent in areas with limited availability of clean drinking water and sanitary conditions. Lately, extensively drug-resistant Salmonella ser. Typhi (XDR S. Typhi) has emerged as one of Pakistan's most challenging public health concerns. Here, we report a case of relapsed typhoid fever in a child, in whom the isolate was found to be resistant to meropenem and azithromycin.

Topics: Anti-Bacterial Agents; Azithromycin; Child; Humans; Salmonella typhi; Sepsis; Serogroup; Typhoid Fever

Sepsis-associated acute kidney injury (SA-AKI) is associated with significant morbidity and mortality. Immune dysregulation is a hallmark of sepsis, with important contributions to organ dysfunction including injury and repair mechanisms in AKI. Macrolide antibiotics, such as azithromycin, have previously demonstrated in preclinical models a myriad of immunomodulatory effects that may benefit critically ill patients with SA-AKI. The aim of this study was to determine if early receipt of azithromycin in SA-AKI is associated with a reduction in major adverse kidney events (MAKE) at hospital discharge.. This was a single center, retrospective cohort study of critically ill adult patients with SA-AKI. Early exposure to azithromycin was defined as receipt of one or more doses within 48 h of a hospital admission with SA-AKI. The primary outcome of MAKE assessed at hospital discharge was the composite of death, requirement for kidney replacement therapy, or a decline in estimated glomerular filtration rate of 25% or more. Multivariable logistic regression was used to account for potential confounders in the assessment.. Of 737 included patients with SA-AKI, 152 (20.6%) received azithromycin. Patients that received early azithromycin were less likely to experience MAKE at hospital discharge when compared to those patients not receiving azithromycin: 38.8% versus 48.4% (P = 0.035). In multivariable logistic regression, receipt of azithromycin was independently associated with a decreased odds of MAKE at hospital discharge (aOR 0.62, 95% CI 0.41-0.93).. Early exposure to azithromycin in SA-AKI is independently associated with lower odds of MAKE at hospital discharge.

Topics: Acute Kidney Injury; Adult; Azithromycin; Critical Illness; Female; Humans; Intensive Care Units; Kidney; Male; Retrospective Studies; Risk Factors; Sepsis

High dose ionizing radiation exposure is associated with myelo-depression leading to pancytopenia and the expected clinical manifestations of acute radiation syndrome (ARS). Herein, we evaluated the efficacy of sargramostim (Leukine. Delayed sargramostim treatment at 48 h post-irradiation significantly reduced mortality (. In a NHP ARS model, sargramostim administered starting at 48 h post-radiation was effective to improve survival, while beneficial hematological effects were observed with sargramostim initiated up to 120 h post exposure.

Topics: Acute Radiation Syndrome; Animals; Azithromycin; Granulocyte-Macrophage Colony-Stimulating Factor; Macaca mulatta; Recombinant Proteins; Sepsis

Sepsis is a life-threatening systemic inflammatory condition triggered as a result of an excessive host immune response to infection. In the past, immunomodulators have demonstrated a protective effect in sepsis. Azithromycin (a macrolide antibiotic) has immunomodulatory activity and was therefore evaluated in combination with ceftriaxone in a clinically relevant murine model of sepsis induced by cecal ligation and puncture (CLP). First, mice underwent CLP and 3 h later were administered the vehicle or a subprotective dose of ceftriaxone (100 mg/kg of body weight subcutaneously) alone or in combination with an immunomodulatory dose of azithromycin (100 mg/kg intraperitoneally). Survival was monitored for 5 days. In order to assess the immunomodulatory activity, parameters such as plasma and lung cytokine (interleukin-6 [IL-6], IL-1β, tumor necrosis factor alpha) concentrations, the plasma glutathione (GSH) concentration, plasma and lung myeloperoxidase (MPO) concentrations, body temperature, blood glucose concentration, and total white blood cell count, along with the bacterial load in blood, peritoneal lavage fluid, and lung homogenate, were measured 18 h after CLP challenge. Azithromycin in the presence of ceftriaxone significantly improved the survival of CLP-challenged mice. Further, the combination attenuated the elevated levels of inflammatory cytokines and MPO in plasma and lung tissue and increased the body temperature and blood glucose and GSH concentrations, which were otherwise markedly decreased in CLP-challenged mice. Ceftriaxone produced a significant reduction in the bacterial load, while coadministration of azithromycin did not produce a further reduction. Therefore, the survival benefit offered by azithromycin was due to immunomodulation and not its antibacterial action. The findings of this study indicate that azithromycin, in conjunction with appropriate antibacterial agents, could provide clinical benefits in sepsis.

Topics: Animals; Azithromycin; Bacterial Load; Ceftriaxone; Disease Models, Animal; Drug Therapy, Combination; Escherichia coli; Escherichia coli Infections; Female; Glutathione; Inflammation; Interleukin-1beta; Interleukin-6; Lipopolysaccharides; Lung; Mice; Sepsis; Tumor Necrosis Factor-alpha

Evidence suggests that β-lactam monotherapy of streptococcal infections may incite stronger inflammation and is inferior to combination therapy with macrolides. We hypothesized that use of macrolides alone or in combination with a β-lactam for group B streptococcal (GBS) sepsis would improve outcomes by reducing inflammation.. TNF-α was measured from supernatants of RAW 264.7 cells stimulated with GBS isolates, in presence of four treatment regimens: ampicillin alone, azithromycin alone, or combination of azithromycin plus ampicillin. Mouse model of GBS sepsis was developed and treated with same four regimens. Clinical sepsis scores were monitored; serum cytokines (TNF-α, IL-6, IL-10) and chemokines (MIP-1α) were measured at the end.. GBS isolates exposed to azithromycin or combination (compared to ampicillin alone) stimulated less TNF production in vitro. In the murine sepsis model, mortality was lower along with decreased sepsis scores in mice treated with combination therapy. Mean serum IL-6 was lower in mice treated with azithromycin alone (66±52 pg/ml) or combination of ampicillin plus azithromycin (52±22 pg/ml) compared to ampicillin alone (260±160 pg/ml) (p<0.005).. Combination therapy of ampicillin+azithromycin improved outcomes in a murine GBS sepsis model; this therapeutic approach deserves additional study.

Topics: Ampicillin; Animals; Anti-Bacterial Agents; Azithromycin; Cell Line; Cytokines; Drug Therapy, Combination; Female; Mice; Sepsis; Streptococcal Infections

To investigate the cost-effectiveness of adding azithromycin to standard cephalosporin regimens of cesarean delivery prophylaxis by considering the maternal outcomes in the current and potential subsequent pregnancies.. A cost-effectiveness model was created using TreeAge to compare the outcomes of using azithromycin-cephalosporin with cephalosporin alone in a theoretical cohort of 700,000 women, the approximate number of nonelective cesarean deliveries annually in the United States that occur during labor or after membrane rupture. Outcomes examined included endometritis, wound infection, sepsis, venous thromboembolism, and maternal death in the current pregnancy and uterine rupture, cesarean hysterectomy, and maternal death in subsequent pregnancies, including cost and quality-adjusted life-years for both pregnancies. Probabilities, utilities, and costs were derived from the literature, and a cost-effectiveness threshold was set at $100,000 per quality-adjusted life-year. Sensitivity analyses were used to determine the robustness of our results.. Compared with cephalosporin alone for prophylaxis, our model showed 16,100 fewer cases of endometritis, 17 fewer cases of sepsis, eight fewer cases of venous thromboembolism, and one fewer maternal death with azithromycin-cephalosporin. Additionally, this strategy prevented 36 uterine ruptures and four cesarean hysterectomies in the subsequent pregnancy. Overall, the addition of azithromycin led to both lower costs and higher quality-adjusted life-years when compared with standard cephalosporin prophylaxis. In sensitivity analysis, we found that as long as the cost of azithromycin remained below $930 (baseline cost $27), it was cost-effective.. For women who undergo cesarean delivery in labor or after membrane rupture, compared with cephalosporin alone, the addition of azithromycin to cesarean delivery infection prophylaxis is less costly and leads to better maternal outcomes in the index delivery and subsequent deliveries. These findings support the use of prophylactic azithromycin at the time of cesarean delivery.

Topics: Anti-Bacterial Agents; Antibiotic Prophylaxis; Azithromycin; Cephalosporins; Cesarean Section; Cost-Benefit Analysis; Endometritis; Female; Humans; Maternal Mortality; Models, Economic; Postoperative Complications; Pregnancy; Sepsis; Surgical Wound Infection

Studies investigating the association between macrolides and outcomes in both pulmonary and nonpulmonary critically ill patients are limited. We aimed to examine the association between azithromycin use and clinical outcomes in severe sepsis patients with and without pneumonia receiving mechanical ventilation.. A retrospective cohort of 105 patients admitted to an adult intensive care unit (ICU) with severe sepsis in an urban university hospital were included in the study. Multivariable linear regression was performed to assess the relationship between azithromycin use and the following outcomes: 28-day ICU-free days and 28-day ventilator-free days.. In univariate analysis, patients receiving azithromycin had nearly 6 more ICU-free days on average than did patients not receiving azithromycin (P = .005). The increased ICU-free days remained in multivariable analysis adjusting for age, sex, race, ICU type, and presence of shock (P = .005). In stratified analysis examining the association of azithromycin use in severe sepsis patients without pneumonia (n = 74), the results were similar to the full cohort.. Azithromycin was associated with more ICU-free days in severe sepsis patients with and without pneumonia. Further investigations are warranted to better elicit the association of macrolide use on clinical outcomes in severe sepsis patients, especially those without pneumonia.

Topics: Adult; Aged; Anti-Bacterial Agents; Azithromycin; Female; Hospitals, University; Humans; Intensive Care Units; Male; Middle Aged; Multivariate Analysis; Outcome Assessment, Health Care; Pneumonia; Respiration, Artificial; Retrospective Studies; Sepsis

Deregulation of inflammasome activation was recently identified to be involved in the pathogenesis of various inflammatory diseases. Although macrolide antibiotics display well described immunomodulatory properties, presumably involved in their clinical effects, their impact on inflammasome activation has not been investigated. We compared the influence of macrolides on cytokine induction in human monocytes. The role of intracellular azithromycin-accumulation was examined by interference with Ca(++)-dependent uptake. We have also analysed the signalling cascades involved in inflammasome activation, and substantiated the findings in a murine sepsis model. Azithromycin, but not clarithromycin or roxithromycin, specifically inhibited IL-1α and IL-1β secretion upon LPS stimulation. Interference with Ca(++)-dependent uptake abolished the cytokine-modulatory effect, suggesting a role of intracellular azithromycin accumulation in the modulatory role of this macrolide. Azithromycin's inhibiting effects were observed upon LPS, but not upon flagellin, stimulation. Consistent with this observation, we found impaired induction of the LPS-sensing caspase-4 whereas NF-κB signalling was unaffected. Furthermore, azithromycin specifically affected IL-1β levels in a murine endotoxin sepsis model. We provide the first evidence of a differential impact of macrolides on the inflammasome/IL-1β axis, which may be of relevance in inflammasome-driven diseases such as chronic obstructive pulmonary disease or asthma.

Topics: Animals; Azithromycin; Calcium; Caspases, Initiator; Cells, Cultured; Cytokines; Disease Models, Animal; Female; Humans; Inflammasomes; Interleukin-1alpha; Interleukin-1beta; Lipopolysaccharides; Macrolides; Mice; Mice, Inbred C57BL; Monocytes; NF-kappa B; Sepsis; Signal Transduction

We report a case of dual infection of scrub typhus and malaria in a 48-year-old woman.

Topics: Animals; Anti-Bacterial Agents; Azithromycin; Chloroquine; Coinfection; Doxycycline; Enzyme-Linked Immunosorbent Assay; Female; Fever; Humans; Immunoglobulin M; Malaria; Middle Aged; Norepinephrine; Orientia tsutsugamushi; Plasmodium vivax; Scrub Typhus; Sepsis; Severity of Illness Index; Treatment Outcome

Utilizing a fully synthetic route to tetracycline analogues, the C-9 side-chain of the fluorocyclines was optimized for both antibacterial activity and oral efficacy. Compounds were identified that overcome both efflux (tet(K), tet(A)) and ribosomal protection (tet(M)) tetracycline-resistance mechanisms and are active against Gram-positive and Gram-negative organisms. A murine systemic infection model was used as an oral efficacy screen to rapidly identify compounds with oral bioavailability. Two compounds were identified that exhibit both oral bioavailability in rat and clinically relevant bacterial susceptibility profiles against major respiratory pathogens. One compound demonstrated oral efficacy in rodent lung infection models that was comparable to marketed antibacterial agents.

Topics: Administration, Oral; Animals; Anti-Bacterial Agents; Biological Availability; Cyclophosphamide; Drug Resistance, Multiple, Bacterial; Female; Gram-Negative Bacteria; Gram-Positive Bacteria; Lung; Male; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Neutropenia; Rats; Rats, Sprague-Dawley; Respiratory Tract Infections; Ribosomes; Sepsis; Stereoisomerism; Structure-Activity Relationship; Tetracycline Resistance; Tetracyclines

Ureaplasma causes sepsis in human neonates. Although erythromycin has been the standard treatment, it is not always effective. No published reports have evaluated Ureaplasma sepsis in a neonatal model. We hypothesized that appropriate antibiotic treatment improves Ureaplasma sepsis in a neonatal mouse model.. Two ATCC strains and two clinical strains of Ureaplasma were evaluated in vitro for antibiotic minimum inhibitory concentration (MIC). In addition, FVB albino mice pups infected with Ureaplasma were randomly assigned to saline, erythromycin, or azithromycin therapy and survival, quantitative blood culture, and growth were evaluated.. MICs ranged from 0.125 to 62.5 µg/ml and 0.25 to 1.0 µg/ml for erythromycin and azithromycin, respectively. The infecting strain and antibiotic selected for treatment appeared to affect survival and bacteremia, but only the infecting strain affected growth. Azithromycin improved survival and bacteremia against each strain, whereas erythromycin was effective against only one of four strains.. We have established a neonatal model of Ureaplasma sepsis and observed that treatment outcome is related to infecting strain and antibiotic treatment. We speculate that appropriate antibiotic selection and dosing are required for effective treatment of Ureaplasma sepsis in neonates, and this model could be used to further evaluate these relationships.

Topics: Animals; Animals, Newborn; Anti-Bacterial Agents; Azithromycin; Bacteremia; Disease Models, Animal; Erythromycin; Female; Humans; Mice; Microbial Sensitivity Tests; Pregnancy; Sepsis; Ureaplasma; Ureaplasma Infections; Ureaplasma urealyticum

Triggering receptor expressed on myeloid cells-1 (TREM-1) is highly expressed in inflammatory lesions caused by infectious agents such as bacteria and fungi but not in normal tissues or non-infectious lesions. There is evidence that macrolide antibiotics can act as immunomodulatory agents. The purpose of the current study was to determine whether azithromycin, a type of macrolide antibiotic, could reduce the expression of TREM-1 in Bacillus pyocyaneus-induced sepsis in vitro and in vivo. We treated THP-1 cells with LPS, LPS+TREM-1/Fc, and LPS+azithromycin for in vitro study. A B. pyocyaneus pyemia animal model was developed for in vivo study. RT-PCR, western blotting, and flow cytometry (FCM) were employed to determine the expression of TREM-1. ELISA analysis was utilized to examine the concentration of cytokines. Our results showed that azithromycin treatment did not reduce the level of LPS-induced TREM-1 mRNA in THP-1 cells. However, treatment with TREM-1/Fc fusion protein or azithromycin reduced the effect of LPS-stimulated TREM-1 protein expression. The expression of inflammatory factors (TNF-α, IL-6, and IL-1β) in cell culture supernatant and mouse serum of the TREM-1/Fc fusion protein-treated and azithromycin-treated groups were lower than that of the control group (p<0.05). The results from the animal sepsis model experiments demonstrated that the TREM-1 Fc/fusion protein and azithromycin treatment groups' survival rates were significantly higher than in the control group. Analysis of serum inflammatory factors in septic mice revealed that the concentration of these factors was significantly lower than in the control group. Our results furthered the understanding of azithromycin function in immunological regulation and provided reliable data for new clinical applications.

Topics: Animals; Azithromycin; Bacillus; Blotting, Western; Cell Line; Disease Models, Animal; Gene Expression; Gram-Positive Bacterial Infections; Immunoconjugates; Immunomodulation; Interleukin-1beta; Interleukin-6; Lipopolysaccharides; Macrophages; Male; Membrane Glycoproteins; Mice; Mice, Inbred BALB C; Receptors, Immunologic; Recombinant Fusion Proteins; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sepsis; Survival Rate; Triggering Receptor Expressed on Myeloid Cells-1; Tumor Necrosis Factor-alpha

Antibiotic treatment of Staphylococcus aureus infections is often problematic due to the slow response to therapy and the high frequency of infection recurrence. The intracellular persistence of staphylococci has been recognized and could offer a good explanation for these treatment difficulties. Knowledge of the interplay between intracellular antibiotic activity and the overall outcome of infection is therefore important. Several intracellular in vitro models have been developed, but few experimental animal models have been published. The mouse peritonitis/sepsis model was used as the basic in vivo model exploring a quantitative ex vivo extra- and intracellular differentiation assay. The intracellular presence of S. aureus was documented by electron microscopy. Five antibiotics, dicloxacillin, cefuroxime, gentamicin, azithromycin, and rifampin (rifampicin), were tested in the new in vivo model; and the model was able to distinguish between their extra- and intracellular effects. The intracellular effects of the five antibiotics could be ranked as follows as the mean change in the log(10) number of CFU/ml (Delta log(10) CFU/ml) between treated and untreated mice after 4 h of treatment: dicloxacillin (3.70 Delta log(10) CFU/ml) > cefuroxime (3.56 Delta log(10) CFU/ml) > rifampin (1.86 Delta log(10) CFU/ml) > gentamicin (0.61 Delta log(10) CFU/ml) > azithromycin (0.21 Delta log(10) CFU/ml). We could also show that the important factors during testing of intracellular activity in vivo are the size, number, and frequency of doses; the time of exposure; and the timing between the start of infection and treatment. A poor correlation between the intracellular accumulation of the antibiotics and the actual intracellular effect was found. This stresses the importance of performing experimental studies, like those with the new in vivo model described here, to measure actual intracellular activity instead of making predictions based on cellular pharmacokinetic and MICs.

Topics: Animals; Animals, Outbred Strains; Anti-Bacterial Agents; Colony Count, Microbial; Dicloxacillin; Dose-Response Relationship, Drug; Female; Humans; Mice; Microbial Sensitivity Tests; Peritoneum; Peritonitis; Rifampin; Sepsis; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome

Mycoplasma pneumoniae is a frequent cause of community-acquired respiratory infections, especially in young children and adolescents. The significance of M. pneumoniae infection in HIV-positive patients, particularly children, is not well described. This report describes an HIV-positive female child with recurrent B-cell lymphoma and recurrent or relapsing pulmonary infections with M. Pneumoniae.

Topics: AIDS-Related Opportunistic Infections; Anti-HIV Agents; Antineoplastic Combined Chemotherapy Protocols; Azithromycin; Child; Doxycycline; Fatal Outcome; Female; HIV Infections; Humans; Lymphoma, AIDS-Related; Mycoplasma pneumoniae; Pneumonia, Mycoplasma; Polymerase Chain Reaction; Recurrence; Sepsis; Zidovudine

Streptomyces species are part of the actinomycetes group. They have rarely been reported as a cause of invasive infection. We report a case of catheter-related Streptomyces bacteremia complicated by severe sepsis and septic thrombosis. We also present a brief review of the literature on Streptomyces bacteremia.

Topics: Aged; Anti-Bacterial Agents; Anti-Infective Agents; Aza Compounds; Azithromycin; Catheterization, Central Venous; Fluoroquinolones; Humans; Male; Minocycline; Moxifloxacin; Quinolines; Sepsis; Streptomyces; Treatment Outcome; Venous Thrombosis

Acute pancreatitis is an important cause of morbidity and mortality, mainly due to sepsis. The aim of this study was to determine the incidence of infectious complications and their impact on mortality in patients hospitalized for acute pancreatitis.. Patients admitted for acute pancreatitis were retrospectively included within a period between 1995 and 2000. Incidence of abdominal and extra-abdominal sepsis and specific care were specifically analyzed. Risk factors for death were evaluated by uni- and multivariated analysis.. Two hundreds and twelve consecutive patients (128 males, median age 54 years) were included. Mortality was 10.8%. At least one infectious episode was collected in 25% of the patients with an abdominal sepsis (26.8%), bacteriemia (24.4%), respiratory (24.4%) and urinary tracts (19.5%) infections. Infection was polymicrobial in 37.5%. An antibiotic prophylaxis was administered in 10.8%, more often in patients with severe pancreatitis. It did not alter mortality or incidence of infections but significantly delayed occurrence of sepsis. Mortality of patients treated with more than one line of antibiotics was higher. However in this study infectious complications were not an independent factor for mortality.. Infections are frequent and polymicrobial but are not an independent prognostic factor during acute pancreatitis.

Topics: Acute Disease; Adult; Age Factors; Aged; Aged, 80 and over; Amoxicillin; Anti-Bacterial Agents; Antibiotic Prophylaxis; APACHE; Azithromycin; Bacterial Infections; Ceftriaxone; Data Interpretation, Statistical; Drug Therapy, Combination; Female; Humans; Incidence; Male; Middle Aged; Pancreatitis; Prognosis; Retrospective Studies; Risk Factors; Sepsis; Time Factors