Evolving antibiotic resistance in Group B Streptococci causing invasive infant disease: 1970-2021.

BACKGROUND: We sought to define the frequency of antibiotic resistance over time in a collection of invasive GBS isolates derived from infant early-onset disease (EOD), late-onset disease (LOD), and late-late onset disease (LLOD). METHODS: A multicenter retrospective review of infants born from 1970 to 2021 with GBS isolated from blood, cerebrospinal fluid, synovial fluid, cellulitis, or bone. All isolates were serotyped and antimicrobial susceptibility testing performed using disk diffusion. RESULTS: The most common serotypes in our 2017 isolates were III (n = 1112, 55.1%), Ia (n = 445, 22%), Ib (n = 182, 9%) and II (n = 146, 7.2%). A total of 945 (46.8%) isolates were from infants with EOD, 976 (48.3%) from LOD, and 96 (4.75%) from LLOD. All isolates were penicillin-susceptible. Compared to strains isolated <2000, strains isolated ≥2000 showed significantly greater frequency of erythromycin (4.0% to 32.3%, P < 0.0001) and clindamycin (1.5% to 17.5%, P < 0.0001) resistance. Year of isolation (≥2000) and serotype V were significantly associated with erythromycin and/or clindamycin resistance. CONCLUSIONS: We document a rapid and significant increase in clindamycin and erythromycin resistance. As clindamycin may be considered in severely penicillin-allergic women needing GBS intrapartum prophylaxis, obstetricians, pediatricians, and neonatologist should be aware of this disturbing trend. IMPACT: Group B streptococcal strains isolated from infants with invasive infection have become more resistant to second-line antibiotics over time. In this epidemiologic study of 2017 group B streptococci isolated from 1970 to 2021, penicillin susceptibility remained uniform; however, resistance to erythromycin and clindamycin increased significantly over time across all capsular serotypes. Clindamycin resistance exceeded 20% by 2010 in most serotypes. While penicillin remains the treatment of choice for group B streptococcal infant disease, pediatricians and neonatologists should be aware of the high prevalence of resistance to clindamycin, a recommended alternative drug used for intrapartum-antibiotic prophylaxis in penicillin-allergic women.

Genomic characterization of emerging invasive Streptococcus agalactiae serotype VIII in Alberta, Canada.

Invasive Group B Streptococcus (GBS) can infect pregnant women, neonates, and older adults. Invasive GBS serotype VIII is infrequent in Alberta; however, cases have increased in recent years. Here, genomic analysis was used to characterize fourteen adult invasive serotype VIII isolates from 2009 to 2021. Trends in descriptive clinical data and antimicrobial susceptibility results were evaluated for invasive serotype VIII isolates from Alberta. Isolate genomes were sequenced and subjected to molecular sequence typing, virulence and antimicrobial resistance gene identification, phylogenetic analysis, and pangenome determination. Multilocus sequencing typing identified eight ST42 (Clonal Complex; CC19), four ST1 (CC1), and two ST2 (CC1) profiles. Isolates were susceptible to penicillin, erythromycin, chloramphenicol, and clindamycin, apart from one isolate that displayed erythromycin and inducible clindamycin resistance. All isolates carried genes for peptide antibiotic resistance, three isolates for tetracycline resistance, and one for macrolide, lincosamide, and streptogramin resistance. All genomes carried targets currently being considered for protein-based vaccines (e.g., pili and/or Alpha family proteins). Overall, invasive GBS serotype VIII is emerging in Alberta, primarily due to ST42. Characterization and continued surveillance of serotype VIII will be important for outbreak prevention, informing vaccine development, and contributing to our understanding of the global epidemiology of this rare serotype.

The Formation and Drug Resistance Mechanism of Biofilm for Streptococcus pneumoniae Infection in Severe Respiratory Patients.

This study was to explore whether Streptococcus pneumoniae would form biofilms and the formative factors of biofilms, as well as the drug resistance mechanism of S. pneumoniae. In this study, a total of 150 strains of S. pneumoniae were collected from 5 local hospitals in the past two years, and the minimum inhibitory concentrations (MIC) of levofloxacin, moxifloxacin and penicillin were determined by agar double dilution method to select the drug-resistant strains. The polymerase chain reaction (PCR) amplification and sequencing were performed on specific genes of drug-resistant strains. In addition, 5 strains of S. pneumoniae with penicillin MIC ≤ 0.065 µg/mL, 0.5 µg/mL, 2 µg/mL, ≥ 4µg/mL were randomly selected, and the biofilms were cultured on two kinds of well plates for 24 hours. Finally, whether the biofilms were formed was observed. Experimental results revealed that the resistance rate of S. pneumoniae to erythromycin in this area was as high as 90.3%, and the strains that were resistant to penicillin account for only 1.5%. The amplification and sequencing experiment revealed that one (strain 1) of the strains, which was resistant to both drugs, had a GyrA mutation and ParE mutation, and strain 2 had a parC mutation. All strains generated biofilms, and the optical density (OD) value of penicillin MIC ≤ 0.065 µg/mL group (0.235 ± 0.053) was higher than that of 0.5 µg/mL group (0.192 ± 0.073) (P< 0.05) and higher than the OD value of the 4 µg/mL group (0.200 ± 0.041) (P< 0.05), showing statistically great differences. It was confirmed that the resistance rate of S. pneumoniae to erythromycin remained high, the rate of sensitivity to penicillin was relatively high, and the moxifloxacin and levofloxacin-resistant strains had appeared; S. pneumoniae mainly showed QRDR mutations in gyrA, parE, and parC; and it was confirmed that S. pneumoniae can generate biofilms in vitro.

Erythromycin Improves the Quality of Esophagogastroduodenoscopy in Upper Gastrointestinal Bleeding: A Network Meta-Analysis.

BACKGROUND/AIM: Upper gastrointestinal bleeding (UGIB) usually requires esophagogastroduodenoscopy (EGD) for diagnostic and-potentially-therapeutic purposes. However, blood within the gastric lumen may hinder the procedure. Administration of prokinetics like erythromycin has shown efficacy. This network meta-analysis investigates the efficacy of this intervention prior to EGD. METHODS: We performed a systematic literature search of Embase, PubMed/Medline, and other databases through March 8, 2022 to include randomized controlled trials (RCTs) comparing prokinetic use in EGD for UGIB. We used the DerSimonian-Laird approach to pool data and compare outcomes including need for repeat endoscopy and blood transfusion. Pooled prevalence of proportional outcomes, 95% confidence interval (CI), and p-values were calculated. RESULTS: We included eight RCTs with four distinct intervention groups (erythromycin, placebo to erythromycin, nasogastric (NG) lavage and NG lavage + erythromycin) published between 2002 and 2020 with a total of 721 patients (mean age 60.0 ± 3.1 years; 73.2% male). The need for second look endoscopy was significantly lower with erythromycin than placebo (relative risk: 0.42, CI 0.22-0.83, p = 0.01). Using the frequentist approach, the combination of NG lavage and erythromycin (92.2) was rated highest, followed by erythromycin alone (73.1) for higher rates of empty stomach. Erythromycin was rated highest for lower need for packed red blood cell transfusion (72.8) as well as mean endoscopy duration (66.0). CONCLUSION: Erythromycin improved visualization at EGD, reduced requirements for blood transfusion and repeat EGD, and shortened hospital stay. The combination of erythromycin and NG lavage showed reduced mortality.

Use of prokinetic agents in hospitalised adult patients: A scoping review.

BACKGROUND: Gastrointestinal motility is important for adequate uptake of fluids and nutrition but is often impaired in hospitalised patients. Prokinetic agents enhance gastrointestinal motility and are prescribed for many hospitalised patients. In this scoping review, we aimed to systematically describe the body of evidence on the use of prokinetic agents in hospitalised patients. We hypothesised, that the body of evidence would be limited and derive from heterogeneous populations. METHODS: We conducted this scoping review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews statement. We searched Medline, Embase, Epistemonikos and the Cochrane Library for studies assessing the use of prokinetic agents on any indication and outcome in adult hospitalised patients. We used a modified version of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) to assess the certainty of evidence. RESULTS: We included 102 studies with a total of 8830 patients. Eighty-six studies were clinical trials (84%), and 52 (60%) of these were conducted in the intensive care unit, with feeding intolerance as the main indication. In the non-intensive care setting the indications were wider; most studies assessed use of prokinetic agents before gastroscopy to improve visualisation. The most studied prokinetic agent was metoclopramide (49% of studies) followed by erythromycin (31%). In total 147 outcomes were assessed with only 67% of the included studies assessing patient-centred outcomes, and with gastric emptying as the most frequently reported outcome. Overall, the data provided no firm evidence on the balance between the desirable and undesirable effects of prokinetic agents. CONCLUSIONS: In this scoping review, we found that the studies addressing prokinetic agents in hospitalised adults had considerable variations in indications, drugs and outcomes assessed, and that the certainty of evidence was judged to be low to very low.

Epidemiological analysis of Group A streptococcus infection diseases among children in Beijing, China under COVID-19 pandemic.

BACKGROUND: Group A streptococcus is human-restricted gram-positive pathogen, responsible for various clinical presentations from mild epidermis infections to life threatened invasive diseases. Under COVID-19 pandemic,. the characteristics of the epidemic strains of GAS could be different. PURPOSE: To investigate epidemiological and molecular features of isolates from GAS infections among children in Beijing, China between January 2020 and December 2021. Antimicrobial susceptibility profiling was performed based on Cinical Laboratory Sandards Institute. Distribution of macrolide-resistance genes, emm types, and superantigens was examined by polymerase chain reaction. RESULTS: 114 GAS isolates were collected which were frequent resistance against erythromycin (94.74%), followed by clindamycin (92.98%), tetracycline (87.72%). Emm12 (46.49%), emm1 (25.44%) were dominant emm types. Distribution of ermB, ermA, and mefA gene was 93.85%, 2.63%, and 14.04%, respectively. Frequent superantigenes identified were smeZ (97.39%), speG (95.65%), and speC (92.17%). Emm1 strains possessed smeZ, ssa, and speC, while emm12 possessed smeZ, ssa, speG, and speC. Erythromycin resistance was predominantly mediated by ermB. Scarlet fever strains harbored smeZ (98.81%), speC (94.05%). Impetigo strains harbored smeZ (88.98%), ssa (88.89%), and speC (88.89%). Psoriasis strains harbored smeZ (100%). CONCLUSIONS: Under COVID-19 pandemic, our collections of GAS infection cutaneous diseases decreased dramatically. Epidemiological analysis of GAS infections among children during COVID-19 pandemic was not significantly different from our previous study. There was a correlation among emm, superantigen gene and disease manifestations. Long-term surveillance and investigation of emm types and superantigens of GAS prevalence are imperative.

Bacterial resistance to commonly prescribed antibiotics was rare among children hospitalised for clinical dysentery.

AIM: Temporal changes in common pathogens that cause clinical dysentery have been described in Europe. We aimed to describe the distribution of pathogens and their antibiotic resistance in hospitalised Israeli children. METHODS: This study retrospectively studied children hospitalised for clinical dysentery, with or without a positive stool culture, from 1 January 2016 to 31 December 2019. RESULTS: We diagnosed 137 patients (65% males), with clinical dysentery at a median age of 3.7 (interquartile range 1.5-8.2) years. Stools were cultured in 135 patients (99%), and the results were positive in 101 (76%). These comprised Campylobacter (44%), Shigella sonnei (27%), non-typhoid Salmonella (18%) and enteropathogenic Escherichia coli (12%). Only one of the 44 Campylobacter cultures was resistant to erythromycin and one of the 12 enteropathogenic Escherichia coli cultures was resistant to ceftriaxone. None of the Salmonella and Shigella cultures were resistant to ceftriaxone or erythromycin. We did not find any pathogens that were associated with a typical clinical presentation or laboratory results on admission. CONCLUSION: The most common pathogen was Campylobacter, in line with recent European trends. Bacterial resistance for commonly prescribed antibiotics was rare, and these findings support the current European recommendations.

Protective Effect of Erythromycin Pre-adaptation on Focal Cerebral Ischemia in Rats and its Changes in TNF-α and nNOS.

Context: Ischemic stroke accounts for 85% of all types of stroke. Ischemic preconditioning can provide protection against cerebral ischemic injury. Erythromycin can induce ischemic preconditioning in brain tissue. Objective: The study intended to investigate the protective effects of erythromycin preconditioning on infarct volume after focal cerebral ischemia in rats and on the expression of tumor necrosis factor-alpha (TNF-α) and neuronal nitric oxide synthases (nNOS) in rat-brain tissue. Design: The research team performed an animal study. Setting: The study took place in the Department of Neurosurgery at the First Hospital of China Medical University in Shenyang, China. Animals: The animals were 60 healthy male Wistar rats, aged 6 to 8 weeks and weighing 270 to 300 g. Intervention: The research team randomly divided the rats into a control group in simple randomization and intervention groups preconditioning them according to their body weights using different concentrations of erythromycin-5, 20, 35, 50, and 65 mg/kg, with 10 rats in each group. The team induced focal cerebral ischemia and reperfusion using a modified, longa-wire embolization method. The control group, also 10 rats, received an injection intramuscularly of normal saline. Outcome Measures: The research team: (1) calculated the volume of cerebral infarction using triphenyltetrazolium chloride (TTC) staining with image analysis software and (2) investigated the effects of erythromycin preconditioning on the expression of TNF-α and nNOS mRNA and protein in the rat-brain tissue using real-time polymerase chain reaction (PCR) and Western blot. Results: Erythromycin preconditioning reduced the volume of cerebral infarction after induction of cerebral ischemia, showing a U-shaped, dose-response relationship, and the cerebral infarction volume significantly decreased in the 20-, 35-, and 50-mg/kg erythromycin preconditioning groups (P < .05). Erythromycin preconditioning at 20-, 35-, and 50-mg/kg significantly down-regulated the mRNA and protein expression of TNF-α in the rat-brain tissue (P < .05), with the 35-mg/kg erythromycin preconditioning group having the most significant downregulation. Erythromycin preconditioning at 20-, 35-, and 50-mg/kg upregulated the mRNA and protein expression of nNOS in the rat-brain tissue (P < .05), with the 35-mg/kg erythromycin preconditioning group having the most significant upregulation of the mRNA and protein of nNOS. Conclusions: Erythromycin preconditioning had a protective effect against focal cerebral ischemia in rats, and the best protective effect occurred for the 35-mg/kg preconditioning. The reason may be related to the fact that erythromycin preconditioning significantly upregulated nNOS and downregulated TNF-α in the brain tissue.

Corneal Culture and Antibiotic Susceptibility Results for Microbial Keratitis in the Mid-Atlantic Region of the United States, 2016 to 2020.

OBJECTIVE: To examine the microbial distribution and antimicrobial susceptibility of culture-positive microbial keratitis at a large tertiary referral center in the mid-Atlantic region of the United States. METHODS: Retrospective review of culture-positive microbial keratitis cases at the Wilmer Eye Institute from 2016 through 2020. RESULTS: Of the 474 culture-positive microbial keratitis cases, most were bacterial (N=450, 94.9%), followed by fungal (N=48, 10.1%) and Acanthamoeba keratitis (N=15, 3.1%). Of the 450 bacterial isolates, 284 (69.5%) were gram-positive organisms, whereas 157 (28.4%) were gram-negative organisms. The most common bacterial species isolated was coagulase-negative Staphylococcus spp (N=154, 24.8%), and the most common gram-negative isolate was Pseudomonas aeruginosa (N=76, 12.3%). Among fungi, the most common isolates were Candida (N=25, 45.4%), whereas Fusarium (N=6, 10.9%) and Aspergillus (N=3, 5.5%) were less common. Of the 217 bacterial isolates tested for erythromycin susceptibility, 121 (55.7%; ∼60% of coagulase-negative staphylococci and corynebacteria tested) showed resistance to erythromycin. CONCLUSIONS: Microbial keratitis in the Baltimore Mid-Atlantic region of the United States is most commonly caused by bacteria, with fungi and acanthamoeba being less common. Gram-positive bacterial infections predominate. Among fungal keratitis cases, Candida species are more commonly encountered than are filamentous species. Use of erythromycin as infection prophylaxis should be reexamined. Findings from our study may guide empiric treatment in this geographic region.

Erythromycin vs azithromycin for treatment of preterm prelabor rupture of membranes: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to estimate the effect of erythromycin vs azithromycin on the duration of latency and the rate of clinical chorioamnionitis in women with preterm prelabor rupture of membranes by performing a systematic review and meta-analysis of the existing literature. DATA SOURCES: From inception to October 2021, we explored MEDLINE, Scopus, Embase, CINAHL, ClinicalTrials.gov, and Cochrane Central Register of Controlled Trials. STUDY ELIGIBILITY CRITERIA: Studies comparing the duration of latency and the rate of clinical chorioamnionitis between women with preterm prelabor rupture of membranes who were treated with erythromycin and those who were treated with azithromycin at the time of diagnosis were included. METHODS: Here, 2 reviewers separately ascertained studies, obtained data, and gauged study quality. The mean length of latency and the rate of clinical chorioamnionitis were compared and mean differences and odds ratios with 95% confidence intervals were estimated. RESULTS: A total of 5 studies with 1289 women were identified. The mean length of latency in women with preterm prelabor rupture of membranes was similar between individuals treated with erythromycin and those treated with azithromycin: 6.6 days vs 6.7 days (mean difference, 0.07 days; 95% confidence interval, -0.45 to 0.60; I2, 0%). The median point prevalence rates of clinical chorioamnionitis were 25% (95% confidence interval, 12-32) in women treated with erythromycin and 14% (95% confidence interval, 9-24) in women treated with azithromycin. The overall clinical chorioamnionitis rate in women treated with azithromycin was lower than women treated with erythromycin (pooled odds ratio, 0.53; 95% confidence interval, 0.39-0.71; I2, 0%). CONCLUSION: The administration of azithromycin in women with preterm prelabor rupture of membranes was associated with a similar latency period but a lower rate of clinical chorioamnionitis than the administration of erythromycin.

Population pharmacokinetic modeling of caffeine in preterm infants with apnea of prematurity: New findings from concomitant erythromycin and AHR genetic polymorphisms.

Current standard-dose caffeine therapy results in significant intersubject variability. The aims of this study were to develop and evaluate population pharmacokinetic (PPK) models of caffeine in preterm infants through comprehensive screening of covariates and then to propose model-informed precision dosing of caffeine for this population. A total of 129 caffeine concentrations from 96 premature neonates were incorporated into this study. Comprehensive medical record and genotype data of these neonates were collected for analysis. PPK modeling was performed by a nonlinear mixed effects modeling program (NONMEM). Final models based on the current weight (CW) or body surface area (BSA) were evaluated via multiple graphic and statistical methods. The model-informed dosing regimen was performed through Monte Carlo simulations. In addition to CW or BSA, postnatal age, coadministration with erythromycin (ERY), and aryl hydrocarbon receptor coding gene (AHR) variant (rs2158041) were incorporated into the final PPK models. Multiple evaluation results showed satisfactory prediction performance and stability of the CW- and BSA-based models. Monte Carlo simulations demonstrated that trough concentrations of caffeine in preterm infants would be affected by concomitant ERY therapy and rs2158041 under varying dose regimens. For the first time, ERY and rs2158041 were found to be associated with the clearance of caffeine in premature infants. Similar predictive performance and stability were obtained for both CW- and BSA-based PPK models. These findings provide novel insights into caffeine precision therapy for preterm infants.

Colostomy as a definitive treatment in an ALS patient with acute colonic Pseudo-obstruction refractory to medical management, a case report.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease, and ALS patients may experience disturbed gastrointestinal motility often resulting in acute colonic pseudo-obstruction (ACPO). There is currently a paucity in the literature to guide the treatment of patients with both ALS and ACPO. CASE PRESENTATION: Here we describe a 39-year-old male patient with advanced ALS who developed ACPO. His condition was refractory to both medical and procedural managements including polyethylene glycol, senna, and docusate suppository, metoclopramide, linaclotide, erythromycin, prucalopride, neostigmine, and repeated colonoscopies. He ultimately underwent successful colostomy for palliation. Here we report the peri-operative multidisciplinary approach taken with this case, the surgical procedures, the potential risks, and the outcome. CONCLUSION: The patient is delighted with the result and requested publication of this case to raise awareness of constipation in ALS patients and promote the consideration of colostomy as a treatment option for patients with ileus resistant to conservative management. Ultimately, a multidisciplinary team approach is required to properly assess the risks and benefits to achieve good clinical outcomes.

Microbiological and clinical characteristics of invasive Group B Streptococcal blood stream infections in children and adults from Qatar.

INTRODUCTION: Group B Streptococci (GBS) colonize almost one third of human gastrointestinal and genitourinary tracts, particularly in females. The aim of this study is to evaluate the epidemiology, microbiological characteristics, and clinical outcomes of invasive GBS disease in Qatar from all age groups. METHODS: A retrospective study was conducted on patients with confirmed GBS blood stream infections during the period between January 2015 and March 2019. Microbiological identification was performed using automated BD PhoenixTM system, while additional antimicrobial susceptibility tests were performed using E test and disc diffusion methods. RESULT: During the four years period, the incidence steadily rose from 1.48 to 2.09 cases per 100.000 population. Out of 196 confirmed cases of invasive GBS infections, the majority were females (63.7%, 125/196) of which 44.8% were pregnant and 53.6% were colonized. Three distinct affected age groups were identified: children ≤ 4 years of age (35.7%), young adults 25-34 (20.9%) and the elderly ≥ 65 year (17.4%). Presenting symptoms were mild with fever in 53% of cases while 89% of cases had Pitt bacteraemia score of ≤ 2. Isolates were universally sensitive to penicillin, ceftriaxone, and vancomycin at 100% but with significant resistance to erythromycin (49%) and clindamycin (28.6%) while 16.8% had inducible clindamycin resistance. Clinical outcomes showed cure rate of 87.25% with complications in (8.76%) and 4% mortality. CONCLUSION: There is a rising trend of Group B Streptococcal blood stream infections in Qatar with significantly high clindamycin and erythromycin resistance rates. Universal susceptibility rates were demonstrated for penicillin, ceftriaxone, and vancomycin.

Effect of erythromycin on mortality and the host response in critically ill patients with sepsis: a target trial emulation.

BACKGROUND: Immunomodulatory therapies that improve the outcome of sepsis are not available. We sought to determine whether treatment of critically ill patients with sepsis with low-dose erythromycin-a macrolide antibiotic with broad immunomodulatory effects-decreased mortality and ameliorated underlying disease pathophysiology. METHODS: We conducted a target trial emulation, comparing patients with sepsis admitted to two intensive care units (ICU) in the Netherlands for at least 72 h, who were either exposed or not exposed during this period to treatment with low-dose erythromycin (up to 600 mg per day, administered as a prokinetic agent) but no other macrolides. We used two common propensity score methods (matching and inverse probability of treatment weighting) to deal with confounding by indication and subsequently used Cox regression models to estimate the treatment effect on the primary outcome of mortality rate up to day 90. Secondary clinical outcomes included change in SOFA, duration of mechanical ventilation and the incidence of ICU-acquired infections. We used linear mixed models to assess differences in 15 host response biomarkers reflective of key pathophysiological processes from admission to day 4. RESULTS: In total, 235 patients started low-dose erythromycin treatment, 470 patients served as controls. Treatment started at a median of 38 [IQR 25-52] hours after ICU admission for a median of 5 [IQR 3-8] total doses in the first course. Matching and weighting resulted in populations well balanced for proposed confounders. We found no differences between patients treated with low-dose erythromycin and control subjects in mortality rate up to day 90: matching HR 0.89 (95% CI 0.64-1.24), weighting HR 0.95 (95% CI 0.66-1.36). There were no differences in secondary clinical outcomes. The change in host response biomarker levels from admission to day 4 was similar between erythromycin-treated and control subjects. CONCLUSION: In this target trial emulation in critically ill patients with sepsis, we could not demonstrate an effect of treatment with low-dose erythromycin on mortality, secondary clinical outcomes or host response biomarkers.

Comparative Effectiveness of Intravenous Azithromycin Versus Erythromycin Stimulating Antroduodenal Motility in Children.

BACKGROUND: Azithromycin has been shown to improve gastrointestinal motility in adults and may have fewer drug interactions and reduced arrhythmogenic effects than erythromycin. We hypothesized that azithromycin is comparable to erythromycin in eliciting pharmacodynamic outcomes for antral and small bowel motility. OBJECTIVE: To compare the pharmacodynamic effectiveness of azithromycin and erythromycin for eliciting antral and duodenal motility in pediatric patients who underwent antroduodenal manometry for different indications. METHODS: We conducted a retrospective comparison of clinic data and manometric pharmacodynamics outcomes in patients who underwent antroduodenal manometry between 2013 and 2017. RESULTS: Fifty-one patients mean age (± standard deviation) 9.7 (5.4) years, received either azithromycin 3 mg/kg (n = 20) or erythromycin 2 mg/kg (n = 31) during antroduodenal manometry. For patients receiving erythromycin, mean area under the curve (AUC) across all eight pressure ports increased from median [95% confidence interval] 2256 [1585, 2602] to 8742 [5876, 11761] mmHg × s (P < 0.001) and mean motility index increased from 8.63 [7.87, 9.42] to 11.98 [11.20, 12.21] (P < 0.001). For patients receiving azithromycin, mean AUC increased from 2255 [1585, 2602] to 8254 [5649, 10470] mmHg × s (P < 0.001) and motility index increased from 8.63 [7.87,9.42] to 11.79 [11.03, 12.21] (P < 0.001). Neither mean stimulated AUC nor mean motility index was significantly different between azithromycin and erythromycin treatments. There was no significant difference in side effects between groups. CONCLUSIONS: Azithromycin and erythromycin have similar pharmacodynamic effects on antral and small bowel contractility in children. Azithromycin should be considered an acceptable alternative to erythromycin as an upper gastrointestinal tract prokinetic for children and has historically had fewer side effects than erythromycin.

Experimental Study on Streptococcus agalactiae Genotype and Erythromycin Resistance in Neonatal Sepsis.

This study aimed to evaluate Streptococcus agalactiae genotype and erythromycin resistance in neonatal sepsis. After obtaining the mothers' informed consent, trained nurses sampled 430 neonatal specimens of sepsis from the ear canal, oral cavity and umbilical cord immediately after childbirth and implemented a cross-sectional study. By Gram staining, morphology, hemolysis mode, catalase and CAMP tests, the isolate was identified as S. agalactiae. All 455 isolates were tested for antimicrobial susceptibility by the disc diffusion method. Multilocus sequence typing was used to serotype S. agalactiae involving sequencing of 7 housekeeping genes. The erythromycin resistance genes-erm (B), erm (A) and mef (A) were detected by PCR. Results showed that there were 286 cases (66.51%) of neonates delivered naturally, and 144 cases (33.49%) of neonates delivered by cesarean section. A total of 455 strains were tested, including 253 strains (55.60%) of Gram-positive bacteria with 100 strains (21.98%) of S. agalactiae and 52 strains (11.43%) of Staphylococcus epidermidis, 178 strains (39.12%) of Gram-negative bacteria with 45 strains of Klebsiella pneumoniae (9.89%), 36 strains of Escherichia coli (7.91%), 36 strains of Pseudomonas aeruginosa (7.91%), and 323 strains of Citrobacter freundii (7.03%). S. agalactiae had the highest resistance of 87 (87.00%) to erythromycin, followed by resistance to azithromycin 83 (83.00%) and clindamycin 78 (78.00%). In children with neonatal sepsis, S. agalactiae serotypes were mainly Ia, Ib, and III, accounting for 29.00%, 35.00%, and 19.00% respectively. The main genotypes were ST651, ST103 and ST176, which account for 19.00%, 17.00% and 15.00% respectively. The ST19 type 13.00%, ST27 type 8.00%, ST17 Type 11.00%, ST10 type 12.00%, ST485 type 5.00%. The ST103 and ST485 isolates were classified as serotype Ia, the ST10 and ST176 isolates were classified as serotype Ib, and ST17 and ST19 isolates were classified as serotype III. Among the strains of S. agalactiae, 40.23% (35/87) carry erm (A) gene, 35.63% (31/87) carry erm (B) gene, and 24.14% (21/87) carry mef (A) gene. erm (A) gene was the most common gene in ST19 strain (7/11, 63.64%), and erm (B) gene was the most common gene in ST176 and ST651 strains (6/12, 50.00%; 8/18, 44.44%), while mef (A) gene was the most common gene in ST17 strain (5/11, 45.45%). In general, S. agalactiae genotypes in neonatal sepsis were mainly ST651, ST103 and ST176, and the main serotypes are Ia, Ib, and III. There was good consistency between ST and serotype, and a significant difference was shown in erythromycin resistance and ST distribution, which highlights the value of new epidemiological trend detection by monitoring multiple characteristics and provides inspiration for the development of multivalent S. agalactiae vaccines.

Reversal of Feed Intolerance by Prokinetics Improves Survival in Critically Ill Cirrhosis Patients.

BACKGROUND AND AIMS: Feed intolerance (FI) is common in cirrhosis patients in intensive care units (ICU). Prokinetics are the first line treatment for FI but their efficacy and safety in critically ill patient with cirrhosis is unknown. We evaluated the role of prokinetics in reversal of FI and clinical outcomes. METHODS: Consecutive patients admitted in ICU developing new-onset FI, were randomized to receive either intravenous metoclopramide (Gr.A, n = 28), erythromycin (Gr.B, n = 27) or placebo (Gr.C, n = 28). FI was defined with the presence of 3 of 5 variables- absence of bowel sounds, gastric residual volume ≥ 500 ml, vomiting, diarrhoea and bowel distension. Primary end-point was complete resolution of FI (≥ 3 variables resolved) within 24-h and secondary end-points included resolution within 72-h and survival at 7-days. RESULTS: Of the 1030 ICU patients, 201 (19.5%) developed FI and 83 patients were randomized. Baseline parameters between the groups were comparable. Complete resolution at 24-h was higher in Gr.A (7.14%) and B (22.2%) than C (0%, p = 0.017). Overall, 58 (69.9%) patients achieved resolution within 72 h, more with metoclopramide (n = 24, 85.7%) and erythromycin (n = 25, 92.6%) than with placebo (n = 9, 32.1%, p < 0.001). The 7-day survival was better in patients who achieved resolution within 72-h (65.5 vs. 36%, p = 0.011) than non-responders. High lactate (OR-3.32, CI-1.45-7.70, p = 0.005), shock at baseline (OR-6.34, CI-1.67-24.1, p = 0.007) and resolution of FI within 72 h (OR-0.11, CI, 0.03-0.51, p = 0.04) predicted 7-day mortality. CONCLUSIONS: FI is common in critically-ill cirrhosis patients and non-resolution carries high mortality. Early recognition and treatment with prokinetics is recommended to improve short-term survival.

Gastrointestinal dysmotility is common in cirrhosis and higher incidence in critically ill patients. Promotility drugs are the first line of medication especially in ICU patients. In our study, we found that feed intolerance is present in nearly one in five critically ill cirrhosis and is associated with higher mortality. Patients who achieve resolution had an improved short-term survival. Prokinetic medications are safe in critically ill cirrhosis and help in early resolution of feed intolerance. Feed intolerance in critically ill cirrhosis should be recognized as an organ dysfunction and approaches for prevention and early diagnosis of feed intolerance could help in improving the outcomes in critical illness.

Different azithromycin protocols for management of preterm prelabour rupture of membranes: a randomized clinical trial.

BACKGROUND: Preterm prelabor rupture of membranes is associated with polymicrobial infection; hence broad-spectrum antibiotics are recommended. Nowadays, Azithromycin is used instead of Erythromycin due to erythromycin shortages, its ease of administration, decreased cost, and better side effect profile. This study aimed to evaluate the efficacy of different azithromycin protocols for the conservative management of preterm prelabor rupture of membranes. METHODS: It was a single-blinded randomized clinical trial including pregnant women at 24-36+6 weeks with viable singleton pregnancies and confirmed preterm prelabor rupture of membranes from January 01, 2020, to June 01, 2021. The participants were randomized into two groups: Group I was made of women who received Azithromycin 1000 mg PO once, and Group II of women who received Azithromycin 500 mg PO once, followed by Azithromycin 250 mg PO daily for four days. The primary study outcome was the length of the latency period from the diagnosis of preterm prelabor rupture of membranes to delivery (days). RESULTS: The latency period in group I was significantly higher than that in Group II (5.80 ± 5.44 days vs. 2.88 ± 2.37; respectively, p = 0.0001). The mean gestational age at the time of delivery was significantly higher in Group I (p = 0.0001). However, postpartum endometritis and respiratory distress syndrome (RDS) rates were significantly higher in Group II (p = 0.003 and p = 0.0001, respectively). CONCLUSION: The higher dose of Azithromycin was associated with better maternal and neonatal outcomes. TRIAL REGISTRATION: Clinical trial identification number: Clinical trial.gov: NCT04202380 (17/ 12/ 2019). Date of registration: 1/1 /2020. Date of initial participant enrollment30 /1/2020. URL of the registration site: https://www. CLINICALTRIALS: gov/ct2/show/NCT04202380.

Colchicine and macrolides: a cohort study of the risk of adverse outcomes associated with concomitant exposure.

Colchicine is increasingly used as the number of potential indications expands. However, it also has a narrow therapeutic index that is associated with bothersome to severe side effects. When concomitantly use with medications inhibiting its metabolism, higher plasma levels will result and increase likelihood of colchicine toxicity. We conducted a cohort study using electronic health records comparing encounters with colchicine plus a macrolide and colchicine with an antibiotic non-macrolide. We assessed the relationship between the two groups using adjusted multivariate logistic regression models and the risk of rhabdomyolysis, pancytopenia, muscular weakness, heart failure, acute hepatic failure and death. 12670 patients on colchicine plus an antibiotic non-macrolide were compared to 2199 patients exposed to colchicine plus a macrolide. Patients exposed to colchicine and a macrolide were majority men (n = 1329, 60.4%) and white (n = 1485, 67.5%) in their late sixties (mean age in years 68.4, SD 15.6). Heart failure was more frequent in the colchicine plus a macrolide cohort (n = 402, 18.3%) vs the colchicine non-macrolide one (n = 1153, 9.1%) (p < 0.0001) and also had a higher mortality rate [(85 (3.87%) vs 289 (2.28%), p < 0.0001 macrolides vs non-macrolides cohorts, respectively]. When the sample was limited to individuals exposed to either clarithromycin or erythromycin and colchicine, the adjusted OR for acute hepatic failure was 2.47 (95% CI 1.04-5.91) and 2.06 for death (95% CI 1.07-3.97). There is a significant increase in the risk of hepatic failure and mortality when colchicine is concomitantly administered with a macrolide. Colchicine should not be used concomitantly with these antibiotics or should be temporarily discontinued to avoid toxic levels of colchicine.

Changes in Streptococcus pneumoniae Susceptibility in Wisconsin: Implications for Clinical Treatment Decisions for Respiratory Infections.

Objective: In 2019, the American Thoracic Society and Infectious Diseases Society of America updated clinical practice guidelines for community-acquired pneumonia (CAP). In contrast to guidelines published in 2007, macrolide monotherapy for outpatients was made a conditional recommendation based on resistance levels. Local knowledge of current antimicrobial susceptibility is needed to guide management of CAP and other bacterial respiratory pathogens. The purpose of this study was to investigate antimicrobial susceptibility profiles and trending for Wisconsin Streptococcus pneumoniae isolates.Design: Multi-center laboratory surveillance, with testing at a central location utilizing standardized susceptibility testing protocols.Methods: Data published by the Wisconsin Department of Health Services (DHS) were augmented with data from the Surveillance of Wisconsin Organisms for Trends in Antimicrobial Resistance and Epidemiology (SWOTARE) program. Data were stratified by invasive or non-invasive sources, as well as DHS region and compared to data compiled from 2006-2010.Results: Susceptibility rates for ≥ 916 invasive S. pneumoniae assessed from 2016-2020 were greater than 91% for ceftriaxone, tetracycline, and fluoroquinolone agents and were generally higher than those from 354 non-invasive isolates. Low susceptibility rates were observed for invasive isolates of penicillin (78.7%) and erythromycin (64.8%) and were even lower for non-invasive isolates (73.8% and 59.9%, respectively). This erythromycin susceptibility rate was a significant reduction from that observed in 2006-2010 (80.4; P < 0.0002). 24.8% of isolates generated an erythromycin MIC ≥ 8 µg/mL. Statewide geographic variability was noted.Conclusions: Rates of S. pneumoniae susceptibility to parenteral penicillins and cephems, and oral tetracycline and fluoroquinolone agents, remain high throughout Wisconsin. However, low oral penicillin susceptibility rates, taken together with declining macrolide susceptibility rates, should cause clinicians to consider alternative treatment options for respiratory tract infections, especially with macrolides.