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Thavamani A, Sankararaman S, Al-Shakhshir H, Retuerto M, Velayuthan S, Sferra TJ, Ghannoum M. Impact of Erythromycin as a Prokinetic on the Gut Microbiome in Children with Feeding Intolerance-A Pilot Study. Antibiotics (Basel) 2023; 12:1606. [PMID: 37998808 PMCID: PMC10668753 DOI: 10.3390/antibiotics12111606] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2023] [Revised: 10/27/2023] [Accepted: 11/01/2023] [Indexed: 11/25/2023] Open
Abstract
BACKGROUND Studies have demonstrated that the gut microbiome changes upon exposure to systemic antibiotics. There is a paucity of literature regarding impact on the gut microbiome by long-term usage of erythromycin ethyl succinate (EES) when utilized as a prokinetic. METHODS Stool samples from pediatric patients with feeding intolerance who received EES (N = 8) as a prokinetic were analyzed for both bacteriome and mycobiome. Age-matched children with similar clinical characteristics but without EES therapy were included as controls (N = 20). RESULTS In both groups, Proteobacteria, Firmicutes, and Bacteroidetes were the most abundant bacterial phyla. Ascomycota was the most abundant fungal phyla, followed by Basidiomycota. There were no significant differences in richness between the groups for both bacterial and fungal microbiome. Alpha diversity (at genus and species levels) and beta diversity (at the genus level) were not significantly different between the groups for both bacterial and fungal microbiome. At the species level, there was a significant difference between the groups for fungal microbiota, with a p-value of 0.029. We also noted that many fungal microorganisms had significantly higher p-values in the EES group than controls at both genera and species levels. CONCLUSIONS In this observational case-control study, the prokinetic use of EES was associated with changes in beta diversity between the groups for mycobiome at the species level. Many fungal microorganisms were significantly higher in the EES group when compared to the controls. Confirmation of these results in larger trials will provide further evidence regarding the impact of EES on gut microbiota when utilized as a prokinetic agent.
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Affiliation(s)
- Aravind Thavamani
- Division of Pediatric Gastroenterology, Hepatology & Nutrition, Department of Pediatrics, UH Rainbow Babies and Children’s Hospital, Cleveland, OH 44106, USA; (A.T.); (S.V.); (T.J.S.)
- Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA
| | - Senthilkumar Sankararaman
- Division of Pediatric Gastroenterology, Hepatology & Nutrition, Department of Pediatrics, UH Rainbow Babies and Children’s Hospital, Cleveland, OH 44106, USA; (A.T.); (S.V.); (T.J.S.)
- Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA
| | - Hilmi Al-Shakhshir
- Department of Radiology and Imaging Sciences, Emory School of Medicine, Atlanta, GA 30307, USA;
- Department of Radiology and Imaging Sciences Atlanta VA Medical Center, Decatur, GA 30033, USA
| | - Mauricio Retuerto
- Center for Medical Mycology, Department of Dermatology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA; (M.R.); (M.G.)
| | - Sujithra Velayuthan
- Division of Pediatric Gastroenterology, Hepatology & Nutrition, Department of Pediatrics, UH Rainbow Babies and Children’s Hospital, Cleveland, OH 44106, USA; (A.T.); (S.V.); (T.J.S.)
- Division of Pediatric Neurogastroenterology and Motility, Department of Pediatrics, Nationwide Children’s Hospital, Columbus, OH 43205, USA
| | - Thomas J. Sferra
- Division of Pediatric Gastroenterology, Hepatology & Nutrition, Department of Pediatrics, UH Rainbow Babies and Children’s Hospital, Cleveland, OH 44106, USA; (A.T.); (S.V.); (T.J.S.)
- Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA
| | - Mahmoud Ghannoum
- Center for Medical Mycology, Department of Dermatology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA; (M.R.); (M.G.)
- Department of Dermatology, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA
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Corsello A, Scatigno L, Govoni A, Zuccotti G, Gottrand F, Romano C, Verduci E. Gut dysmotility in children with neurological impairment: the nutritional management. Front Neurol 2023; 14:1200101. [PMID: 37213895 PMCID: PMC10196023 DOI: 10.3389/fneur.2023.1200101] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2023] [Accepted: 04/20/2023] [Indexed: 05/23/2023] Open
Abstract
Intestinal motility disorders represent a frequent problem in children with neurological impairment. These conditions are characterized by abnormal movements of the gut, which can result in symptoms such as constipation, diarrhea, reflux, and vomiting. The underlying mechanisms leading to dysmotility are various, and the clinical manifestations are often nonspecific. Nutritional management is an important aspect of care for children with gut dysmotility, as it can help to improve their quality of life. Oral feeding, when safe and in the absence of risk of ingestion or severe dysphagia, should always be encouraged. When oral nutrition is insufficient or potentially harmful, it is necessary to switch to an enteral by tube or parenteral nutrition before the onset of malnutrition. In most cases, children with severe gut dysmotility may require feeding via a permanent gastrostomy tube to ensure adequate nutrition and hydration. Drugs may be necessary to help manage gut dysmotility, such as laxatives, anticholinergics and prokinetic agents. Nutritional management of patients with neurological impairment often requires an individualized care plan to optimize growth and nutrition and to improve overall health outcomes. This review tries to sum up most significant neurogenetic and neurometabolic disorders associated with gut dysmotility that may require a specific multidisciplinary care, identifying a proposal of nutritional and medical management.
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Affiliation(s)
- Antonio Corsello
- Department of Pediatrics, Vittore Buzzi Children’s Hospital, University of Milan, Milan, Italy
| | - Lorenzo Scatigno
- Department of Pediatrics, Vittore Buzzi Children’s Hospital, University of Milan, Milan, Italy
| | - Annalisa Govoni
- Department of Pediatrics, Vittore Buzzi Children’s Hospital, University of Milan, Milan, Italy
| | - Gianvincenzo Zuccotti
- Department of Pediatrics, Vittore Buzzi Children’s Hospital, University of Milan, Milan, Italy
- Department of Biomedical and Clinical Sciences L. Sacco, University of Milan, Milan, Italy
| | - Frédéric Gottrand
- Department of Pediatric Gastroenterology, Hepatology, and Nutrition, CHU Lille, University of Lille, Lille, France
| | - Claudio Romano
- Pediatric Gastroenterology and Cystic Fibrosis Unit, Department of Human Pathology in Adulthood and Childhood "G. Barresi", University of Messina, Messina, Italy
| | - Elvira Verduci
- Department of Pediatrics, Vittore Buzzi Children’s Hospital, University of Milan, Milan, Italy
- Department of Health Science, University of Milan, Milan, Italy
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Di Nardo G, Zenzeri L, Guarino M, Molfino A, Parisi P, Barbara G, Stanghellini V, De Giorgio R. Pharmacological and nutritional therapy of children and adults with chronic intestinal pseudo-obstruction. Expert Rev Gastroenterol Hepatol 2023; 17:325-341. [PMID: 36939480 DOI: 10.1080/17474124.2023.2193887] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2022] [Accepted: 03/18/2023] [Indexed: 03/21/2023]
Abstract
INTRODUCTION Chronic intestinal pseudoobstruction (CIPO) is a rare, heterogenous, and severe form of gastrointestinal dysmotility. AREAS COVERED Pertinent literature on pediatric and adult CIPO management has been assessed via PubMed, Scopus, and EMBASE from inception to June 2022. Prokinetics, aimed at restoring intestinal propulsion (e.g. orthopramides and substituted benzamides, acetyl cholinesterase inhibitors, serotonergic agents, and others), have been poorly tested and the available data showed only partial efficacy. Moreover, some prokinetic agents (e.g. orthopramides and substituted benzamides) can cause major side effects. CIPO-related small intestinal bacterial overgrowth requires treatment preferably via poorly absorbable antibiotics to avoid bacterial resistance. Apart from opioids, which worsen gut motility, analgesics should be considered to manage visceral pain, which might dominate the clinical manifestations. Nutritional support, via modified oral feeding, enteral, or parenteral nutrition, is key to halting CIPO-related malnutrition. EXPERT OPINION There have been significant roadblocks preventing the development of CIPO treatment. Nonetheless, the considerable advancement in neurogastroenterology and pharmacological agents cast hopes to test the actual efficacy of new prokinetics via well-designed clinical trials. Adequate dietary strategies and supplementation remain of crucial importance. Taken together, novel pharmacological and nutritional options are expected to provide adequate treatments forthese patients.
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Affiliation(s)
- Giovanni Di Nardo
- NESMOS Department, Faculty of Medicine & Psychology, Sapienza University of Rome, Sant'Andrea University Hospital, Rome, Italy
| | - Letizia Zenzeri
- NESMOS Department, Faculty of Medicine & Psychology, Sapienza University of Rome, Sant'Andrea University Hospital, Rome, Italy
- Emergency Unit, Santobono-Pausilipon Children's Hospital, Naples, Italy
| | - Matteo Guarino
- Department of Translational Medicine, University of Ferrara, Ferrara, Italy
| | - Alessio Molfino
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Pasquale Parisi
- NESMOS Department, Faculty of Medicine & Psychology, Sapienza University of Rome, Sant'Andrea University Hospital, Rome, Italy
| | - Giovanni Barbara
- Division of Internal Medicine, IRCCS Azienda Ospedaliero-Universitaria Di Bologna; Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Vincenzo Stanghellini
- Division of Internal Medicine, IRCCS Azienda Ospedaliero-Universitaria Di Bologna; Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Roberto De Giorgio
- Department of Translational Medicine, University of Ferrara, Ferrara, Italy
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Proesmans M, Vermeulen F, Boon M. Understanding and managing respiratory infections in children and young adults with neurological impairment. Expert Rev Respir Med 2023; 17:203-211. [PMID: 36932917 DOI: 10.1080/17476348.2023.2192483] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/19/2023]
Abstract
INTRODUCTION Patients with neurocognitive impairment (NI) have multiple medical needs, with respiratory problems leading to an important reduction in quality of life and life expectancy. We aimed to explain that the origin of chronic respiratory symptoms in patients with NI is multifactorial. AREAS COVERED In people with NI there is a high prevalence of swallowing dysfunction and hypersalivation inducing aspiration; cough efficacy is decreased resulting in chronic lung infection; sleep-disordered breathing is frequent and muscle mass is abnormal due to malnutrition. Technical investigations are not always specific and sensitive enough to better diagnose the causes of the respiratory symptoms; moreover, they can sometimes be difficult to perform in this vulnerable patient population. We provide a clinical pathway to adopt to identify, prevent, and treat respiratory complications in children and young adults with NI. A holistic approach in discussion with all care providers and the parents is highly recommended. EXPERT OPINION The care for people with NI and chronic respiratory problems is challenging. The interplay between several causative factors may be difficult to entangle. Well-performed clinical research in this field is largely missing and should be encouraged. Only then, evidence-based clinical care will become possible for this vulnerable patient group.
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Affiliation(s)
- Marijke Proesmans
- KU Leuven, Department of Development and Regeneration, Woman and Child Unit, CF Research Lab, Leuven, Belgium
- Department of Pediatrics, Pediatric Pulmonology, University Hospital Leuven, Leuven, Belgium
| | - Francois Vermeulen
- KU Leuven, Department of Development and Regeneration, Woman and Child Unit, CF Research Lab, Leuven, Belgium
- Department of Pediatrics, Pediatric Pulmonology, University Hospital Leuven, Leuven, Belgium
| | - Mieke Boon
- KU Leuven, Department of Development and Regeneration, Woman and Child Unit, CF Research Lab, Leuven, Belgium
- Department of Pediatrics, Pediatric Pulmonology, University Hospital Leuven, Leuven, Belgium
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Hair AB, Good M. Dilemmas in feeding infants with intestinal failure: a neonatologist's perspective. J Perinatol 2023; 43:114-119. [PMID: 36127395 DOI: 10.1038/s41372-022-01504-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2022] [Revised: 08/17/2022] [Accepted: 08/26/2022] [Indexed: 02/07/2023]
Abstract
Intestinal failure in neonatal and pediatric populations can be debilitating for patients and difficult to manage for clinicians. Management strategies include referral to an intestinal rehabilitation center, small volume trophic feeds to stimulate the intestine with cautious advancement of enteral nutrition using a standardized and evidence-based feeding protocol, and supplemental parenteral nutrition to optimize an infant's growth and nutrition. In this review, we discuss the causes of intestinal failure, parenteral nutrition strategies, enteral feeding initiation and advancement protocols, as well as the challenges in feeding an infant with intestinal failure.
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Affiliation(s)
- Amy B Hair
- Division of Neonatology, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, 77030, USA
| | - Misty Good
- Division of Neonatal-Perinatal Medicine, Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
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Abstract
OBJECTIVES Antroduodenal manometry (ADM) is used to evaluate antral and small intestinal motility, with the presence of phase III migrating motor complexes (MMCs) indicating an intact enteric neuromuscular system. The lack of evidence-based or consensus-driven established norms for MMC in fasting phase and after provocative testing marks a major limitation in the interpretation of ADM studies. We aimed to determine the characteristics of MMC in fasting and post-provocative phase in children. METHODS Data from subjects ages <20 years with ADM results evaluated at neuro-gastroenterology and Motility Disorders Center, Cincinnati Children's Hospital Medical Center from January 2018 to March 2019 were analyzed. RESULTS Forty-eight ADM tracings that did not demonstrate abnormal patterns were included; the mean age was 10.00 ± 5.72 years and 50% were male. Indications for ADM included: vomiting (27.1%), feeding intolerance (27.1%), abdominal pain (16.6%), nausea (14.6%), and abdominal distension (14.6%). Thirty-seven percent of subjects had enteral access for feeds. During fasting, one-third of all MMC originated in the antrum. Azithromycin-induced MMC occurred in 28% of subjects and two-thirds of these originated in the antrum with antral contractions of significantly higher frequency and amplitude compared to fasting. Octreotide significantly increased frequency, amplitude, and duration of MMC compared to fasting, with 76% originating in the antrum. Both azithromycin and octreotide induced more than one MMC in a third of subjects. CONCLUSIONS We describe the characteristics of antral and small intestinal motility during fasting and after provocative testing in children. These values will help standardize our interpretation of pediatric ADM studies.
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Basu S, Smith S. Macrolides for the prevention and treatment of feeding intolerance in preterm low birth weight infants: a systematic review and meta-analysis. Eur J Pediatr 2021; 180:353-378. [PMID: 33044576 DOI: 10.1007/s00431-020-03814-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2020] [Revised: 09/13/2020] [Accepted: 09/15/2020] [Indexed: 12/12/2022]
Abstract
The role of macrolides for the prevention and treatment of feeding intolerance (FI) in preterm low birth weight (LBW) infants has not been well established. To assess the efficacy and safety of macrolides to prevent or treat FI in preterm LBW infants. A systematic review and meta-analysis (PROSPERO ID: CRD42020170519) was conducted for English articles published since inception to March 2020, using MEDLINE, EMBASE, and the Cochrane Controlled Trials Register. Search terms included preterm low birth weight infants, macrolides, erythromycin, azithromycin, clarithromycin, and feeding intolerance. Randomized controlled trials (RCTs) assessing the effects of macrolide therapy on the time to achieve full enteral feeding (FEF;150 mL/kg/day), duration of parenteral nutrition (PN), hospitalization, and adverse events in preterm LBW infants were included. Independent extraction of data was done by both authors using predefined data-sheet. Very-low to low-quality evidence from 21 RCTs, 19 for erythromycin (prophylaxis-6, rescue-13) and 2 for clarithromycin (prophylaxis-1, rescue-1) demonstrated a significantly beneficial role of erythromycin for an earlier FEF, both as a prophylaxis (SMD-0.53, 95% CI - 0.74,- 0.33; 6 studies, n = 368) as well as rescue (SMD-1.16, 95% CI - 1.88, - 0.44; 11 studies, n = 664). Rescue therapy was also beneficial for a significant reduction in the duration of PN, hospitalization, incidences of sepsis, necrotizing enterocolitis, and cholestasis. No arrhythmia or infantile hypertrophic pyloric stenosis was reported.Conclusions: Erythromycin therapy, both as prophylaxis and rescue, is beneficial to reduce the time to achieve FEF in preterm LBW infants, at no higher risk of adverse events.Trial registration: PROSPERO ID: CRD42020170519.
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Affiliation(s)
- Sriparna Basu
- Department of Neonatology, All India Institute of Medical Sciences, Rishikesh, India.
| | - Susan Smith
- School of Health Sciences, University of Southampton, Southampton, UK
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Abstract
OBJECTIVE Gastroesophageal reflux disease (GERD) in premature neonates may manifest as apnea, bradycardia, growth failure, aspiration, or feeding intolerance. Erythromycin ethylsuccinate (EES), is often used as a pro-kinetic in the management of GERD, despite lack of evidence or safety from randomized controlled trials. We sought to study the efficacy of enteral EES at a dose of 50 mg · kg · day in decreasing the frequency of gastroesophageal reflux events as determined by pH-multichannel intraluminal impedance (pH-MII) monitoring. METHODS In a randomized, double-blind, placebo-controlled trial, eligible premature neonates with clinical signs of GERD underwent 24-hour pH-MII monitoring. If >5 reflux events were identified on pH-MII, then subjects were randomized to receive either EES or placebo. Repeat 24-hour pH-MII was performed on day 7 of study treatment and compared to initial pH-MII. RESULTS Forty-three premature neonates were enrolled. Of those, 31 neonates were randomized, 15 to EES and 16 to placebo with a median (IQR) pretreatment total reflux events per 24 hours of 23 (16-40) and 29 (12-40), respectively. Day 7 total events per 24 hours decreased by 4 events in the EES group to 19 (15-33) and by 10 events in the placebo group to 19 (11-26) (P = 0.09). There were no differences in pretreatment and day 7 acidic and nonacidic reflux, proximal reflux, total or percent reflux time, median or longest bolus clearance time, or nurse-reported apnea events between groups. CONCLUSIONS Enteral EES did not decrease reflux events on 24-hour pH-MII at the dose studied. Therefore, it may be ineffective in the treatment of GERD in premature neonates.
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Somarajan S, Muszynski ND, Hawrami D, Olson JD, Cheng LK, Bradshaw LA. Noninvasive Magnetogastrography Detects Erythromycin-Induced Effects on the Gastric Slow Wave. IEEE Trans Biomed Eng 2018; 66:327-334. [PMID: 29993499 DOI: 10.1109/tbme.2018.2837647] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE The prokinetic action of erythromycin is clinically useful under conditions associated with gastrointestinal hypomotility. Although erythromycin is known to affect the electrogastrogram, no studies have examined the effects that erythromycin has on gastric slow wave magnetic fields. METHODS In this study, gastric slow wave activity was assessed simultaneously using noninvasive magnetogastrogram (MGG), electrogastrogram, and mucosal electromyogram recordings. Recordings were obtained for 30 min prior to and 60 min after intravenous administration of erythromycin at dosages of 3 and 6 mg/kg. RESULTS MGG recordings showed significant changes in the percentage power distribution of gastric signal after infusion of both 3 and 6 mg/kg erythromycin at t = 1-5 min that persisted for t = 30-40 min after infusion. These changes agree with the changes observed in the electromyogram. We did not observe any statistically significant difference in MGG amplitude before or after injection of either 3 or 6 mg/kg erythromycin. Both 3 and 6 mg/kg erythromycin infusion showed retrograde propagation with a statistically significant decrease in slow wave propagation velocity 11-20 min after infusion. Propagation velocity started returning toward baseline values after approximately 21-30 min for the 3 mg/kg dosage and after 31-40 min for a dosage of 6 mg/kg. CONCLUSION Our results showed that the magnetic signatures were sensitive to disruptions in normal slow wave activity induced by pharmacological and prokinetic agents such as erythromycin. SIGNIFICANCE This study shows that repeatable noninvasive bio-electro-magnetic techniques can objectively characterize gastric dysrhythmias and may quantify treatment efficacy in patients with functional gastric disorders.
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Abstract
This relationship between gastroesophageal reflux and airway disorders is complex, possibly bidirectional, and not clearly defined. The tools used to investigate gastroesophageal reflux are mostly informative about involvement of gastroesophageal reflux within the gastrointestinal tract, although they are often utilized to study the relationship between gastroesophageal reflux and airway issues with are suspected to occur in relation to reflux. These modalities often lack specificity for reflux-related airway disorders. Co-incidence of gastroesophageal reflux and airway disorders does not necessarily infer causality. While much of our focus has been on managing acidity, controlling refluxate is an area that has not been traditionally aggressively pursued. Our management approach is based on some of the evidence presented, but also often from a lack of adequate study to provide further guidance.
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Affiliation(s)
- Asim Maqbool
- Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, The Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA.
| | - Matthew J Ryan
- Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, The Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA
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Wallis A, Ball M, Butt H, Lewis DP, McKechnie S, Paull P, Jaa-Kwee A, Bruck D. Open-label pilot for treatment targeting gut dysbiosis in myalgic encephalomyelitis/chronic fatigue syndrome: neuropsychological symptoms and sex comparisons. J Transl Med 2018; 16:24. [PMID: 29409505 PMCID: PMC5801817 DOI: 10.1186/s12967-018-1392-z] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2017] [Accepted: 01/20/2018] [Indexed: 01/18/2023] Open
Abstract
BACKGROUND Preliminary evidence suggests that the enteric microbiota may play a role in the expression of neurological symptoms in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Overlapping symptoms with the acute presentation of D-lactic acidosis has prompted the use of antibiotic treatment to target the overgrowth of species within the Streptococcus genus found in commensal enteric microbiota as a possible treatment for neurological symptoms in ME/CFS. METHODS An open-label, repeated measures design was used to examine treatment efficacy and enable sex comparisons. Participants included 44 adult ME/CFS patients (27 females) from one specialist medical clinic with Streptococcus viable counts above 3.00 × 105 cfu/g (wet weight of faeces) and with a count greater than 5% of the total count of aerobic microorganisms. The 4-week treatment protocol included alternate weeks of Erythromycin (400 mg of erythromycin as ethyl succinate salt) twice daily and probiotic (D-lactate free multistrain probiotic, 5 × 1010 cfu twice daily). 2 × 2 repeated measures ANOVAs were used to assess sex-time interactions and effects across pre- and post-intervention for microbial, lactate and clinical outcomes. Ancillary non-parametric correlations were conducted to examine interactions between change in microbiota and clinical outcomes. RESULTS Large treatment effects were observed for the intention-to-treat sample with a reduction in Streptococcus viable count and improvement on several clinical outcomes including total symptoms, some sleep (less awakenings, greater efficiency and quality) and cognitive symptoms (attention, processing speed, cognitive flexibility, story memory and verbal fluency). Mood, fatigue and urine D:L lactate ratio remained similar across time. Ancillary results infer that shifts in microbiota were associated with more of the variance in clinical changes for males compared with females. CONCLUSIONS Results support the notion that specific microorganisms interact with some ME/CFS symptoms and offer promise for the therapeutic potential of targeting gut dysbiosis in this population. Streptococcus spp. are not the primary or sole producers of D-lactate. Further investigation of lactate concentrations are needed to elucidate any role of D-lactate in this population. Concurrent microbial shifts that may be associated with clinical improvement (i.e., increased Bacteroides and Bifidobacterium or decreased Clostridium in males) invite enquiry into alternative strategies for individualised treatment. Trial Registration Australian and New Zealand Clinical Trial Registry (ACTRN12614001077651) 9th October 2014. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=366933&isReview=true.
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Affiliation(s)
- Amy Wallis
- Psychology Department, College of Health and Biomedicine, Victoria University, Melbourne, Australia
| | - Michelle Ball
- Psychology Department, College of Health and Biomedicine, Victoria University, Melbourne, Australia
| | - Henry Butt
- Bioscreen (Aust) Pty Ltd., Melbourne, Australia
| | | | - Sandra McKechnie
- College of Engineering and Science, Victoria University, Melbourne, Australia
| | | | - Amber Jaa-Kwee
- College of Engineering and Science, Victoria University, Melbourne, Australia
| | - Dorothy Bruck
- Psychology Department, College of Health and Biomedicine, Victoria University, Melbourne, Australia
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Duvoisin G, Krishnan U. Gastric Function in Children with Oesophageal Atresia and Tracheoesophageal Fistula. Front Pediatr 2017; 5:76. [PMID: 28447027 PMCID: PMC5388682 DOI: 10.3389/fped.2017.00076] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2017] [Accepted: 03/29/2017] [Indexed: 01/14/2023] Open
Abstract
Oesophageal atresia and tracheoesophageal fistula (OA-TOF) are a multifaceted condition which affects patients throughout their lives. Even though it is one of the most common gastrointestinal malformations, most of the current studies focus on gastro-oesophageal reflux disease, anastomotic strictures, and feeding difficulties. However, there is increasing evidence that a proportion of patients with OA-TOF also have abnormal gastric function. This review aims to provide a comprehensive understanding of studies of gastric function in patients with OA-TOF. The etiology of this abnormality has been hypothesized to be congenital and/or acquired. Several modalities are currently available for the investigation of gastric function, each of them trying to answer specific clinical questions. This review summarizes the studies that have looked at gastric function in the OA-TOF cohort with gastric emptying studies (gastric emptying scintigraphy and 13C octanoic breath test), gastric manometry, electrogastrography, and oral glucose tolerance test. However, these modalities are limited due to poor age-specific normative values and heterogeneous methodologies used. The evaluation of symptoms in this cohort is crucial, modalities for abnormal gastric function are also described. With appropriate investigations and symptoms questionnaires, treatment strategies can be implemented to correct abnormal gastric function and thereby improve the outcomes and quality of life of patients with OA-TOF. This review highlights the need for large international multicentre collaborative studies and high-quality prospective randomized controlled trials to improve our understanding of gastric function in this cohort.
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Affiliation(s)
- Gilles Duvoisin
- Department of Paediatric Gastroenterology, Sydney Children's Hospital, Randwick, NSW, Australia.,Department of Paediatrics, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland
| | - Usha Krishnan
- Department of Paediatric Gastroenterology, Sydney Children's Hospital, Randwick, NSW, Australia.,School of Women's and Children's Health, University of New South Wales, Kensington, NSW, Australia
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Tillman EM, Smetana KS, Bantu L, Buckley MG. Pharmacologic Treatment for Pediatric Gastroparesis: A Review of the Literature. J Pediatr Pharmacol Ther 2016; 21:120-32. [PMID: 27199619 DOI: 10.5863/1551-6776-21.2.120] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
There have been a number of agents that have been tried for treatment of gastroparesis over the past 3 decades, with varying levels of success. Guidelines exist for the management of gastroparesis in adults; however, even though the cause of gastroparesis in children is similar to that in adults, no guidelines exist for treating pediatric gastroparesis as studies on the topic are limited. With what little information we have on pediatric gastroparesis, medications used in children's studies do not seem to demonstrate the same results as in adult patients with gastroparesis; thus, future studies of whether certain medications are effective for treating pediatric gastroparesis and at what dose still need to be conducted. Pharmacological treatment options for pediatric gastroparesis do not show a clear correlation of resolving or even maintaining gastroparesis-associated symptoms or disease state. This article reviews the available studies of drugs that have shown some efficacy, with an emphasis on pediatric studies.
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Affiliation(s)
- Emma M Tillman
- Department of Clinical Pharmacy, The University of Tennessee Health Science Center, Memphis, Tennessee
| | - Keaton S Smetana
- Department of Pharmacy, University of Kentucky Heathcare, Lexington, Kentucky
| | - Likeselam Bantu
- Department of Clinical Pharmacy, The University of Tennessee Health Science Center, Memphis, Tennessee
| | - Merrion G Buckley
- Department of Clinical Pharmacy, The University of Tennessee Health Science Center, Memphis, Tennessee
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Yeh AM, Golianu B. Integrative Treatment of Reflux and Functional Dyspepsia in Children. CHILDREN (BASEL, SWITZERLAND) 2014; 1:119-33. [PMID: 27417471 PMCID: PMC4928719 DOI: 10.3390/children1020119] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 06/06/2014] [Revised: 07/24/2014] [Accepted: 07/29/2014] [Indexed: 01/10/2023]
Abstract
Gastroesophageal reflux disease (GERD) and functional dyspepsia (FD) are common problems in the pediatric population, with up to 7% of school-age children and up to 8% of adolescents suffering from epigastric pain, heartburn, and regurgitation. Reflux is defined as the passage of stomach contents into the esophagus, while GERD refers to reflux symptoms that are associated with symptoms or complications-such as pain, asthma, aspiration pneumonia, or chronic cough. FD, as defined by the Rome III classification, is a persistent upper abdominal pain or discomfort, not related to bowel movements, and without any organic cause, that is present for at least two months prior to diagnosis. Endoscopic examination is typically negative in FD, whereas patients with GERD may have evidence of esophagitis or gastritis either grossly or microscopically. Up to 70% of children with dyspepsia exhibit delayed gastric emptying. Treatment of GERD and FD requires an integrative approach that may include pharmacologic therapy, treating concurrent constipation, botanicals, mind body techniques, improving sleep hygiene, increasing physical activity, and traditional Chinese medicine and acupuncture.
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Affiliation(s)
- Ann Ming Yeh
- Department of Pediatrics, Stanford University, 750 Welch Road, Suite 116, Palo Alto, CA 94304, USA.
| | - Brenda Golianu
- Department of Anesthesiology, Stanford University, 300 Pasteur Dr. Stanford, CA 94304, USA.
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15
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Erythromycin versus neomycin in the treatment of hepatic encephalopathy in cirrhosis: a randomized double-blind study. BMC Gastroenterol 2013; 13:13. [PMID: 23324408 PMCID: PMC3551652 DOI: 10.1186/1471-230x-13-13] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2012] [Accepted: 01/12/2013] [Indexed: 01/19/2023] Open
Abstract
Background Hepatic encephalopathy (HE) is a severe complication in patients with hepatic cirrhosis, which causes numerous hospital admissions and deaths. Antibiotics are the best options in HE treatment, but head-to-head comparisons between these drugs are scarce. Erythromycin combines the antimicrobial effect and prokinetic properties in the same drug, but it has never been used in HE treatment. Our aim was to evaluate the efficacy of erythromycin as an HE treatment. Methods We achieved a randomized controlled trial of adult patients with HE and hepatic cirrhosis admitted in our hospital. After randomization, the subjects received either erythromycin 250 mg or neomycin 1 g orally QID until hospital discharge or prescription of another antibiotic. All subjects were blindly evaluated every day towards quantifying clinical, neuropsychometric, hepatic and renal exams. Statistical analysis was employed to compare the groups and correlate the variables with hospitalization duration. Results 30 patients were evaluated (15 treated with each drug). At hospital admission, the groups were homogeneous, but the erythromycin group subjects achieved a shorter hospitalization stay (p = 0.032) and a more expressive reduction in alanine aminotranspherase levels (p = 0.026). Hospitalization duration was positively correlated with C reactive protein levels measured previous to (p = 0.015) and after treatment (p = 0.01). Conclusions In the sample evaluated erythromycin was associated with significant reductions in hospital stay and in alanine aminotranspherase values. Hospitalization time was positive correlated with C reactive protein levels measured before and after the treatments.
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16
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Melter M, Buderus S. Pharmakologische Aspekte. PÄDIATRISCHE GASTROENTEROLOGIE, HEPATOLOGIE UND ERNÄHRUNG 2013. [PMCID: PMC7498793 DOI: 10.1007/978-3-642-24710-1_47] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Kortikosteroide waren die ersten Therapeutika zur Kontrolle von Abstoßungsreaktionen nach Transplantation. Sie sind seit Langem und immer noch wichtiger Bestandteil vieler immunsuppressiver Therapiekonzepte. Kortikosteroide besitzen zahlreiche antiinflammatorische und immunsuppressive Effekte. Sie beeinflussen über die Bindung spezifischer zytoplasmatischer Rezeptoren die Gentranskriptionsrate für zentrale, immunregulatorische Proteine wie Interleukin 1β (IL-1β), IL-6, Tumor-Nekrose-Faktor α (TNF-α) mit resultierender Suppression der Makrophagenfunktion und konsekutiver T-Zell-Aktivierung. Sie inhibieren auch die IL-2-Synthese, hemmen damit die T-Zell-Proliferation und reduzieren die IL- 2-Rezeptorbindungsfähigkeit. Andererseits stimulieren sie die Synthese des inhibierenden Zytokins „transforming growth factor β“ (TGF-β), was in einem „antiinflammatorisch“ geprägten T-Helfer-Zell-2-artigen Zytokinprofil resultiert. Über die Inhibition der Expression von interferonabhängigen Adhäsionsmolekülen (einschließlich MHC-Klasse-II-Moleküle) bewirken Kortikosteroide darüber hinaus die Alteration von Leukozytenverkehr und -transmigration sowie eine Induktion der Lymphozytenapoptose.
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17
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Preclinical electrogastrography in experimental pigs. Interdiscip Toxicol 2011; 3:53-8. [PMID: 21217873 PMCID: PMC2984130 DOI: 10.2478/v10102-010-0011-5] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2010] [Revised: 05/20/2010] [Accepted: 06/03/2010] [Indexed: 12/21/2022] Open
Abstract
Surface electrogastrography (EGG) is a non-invasive means of recording gastric myoelectric activity or slow waves from cutaneous leads placed over the stomach. This paper provides a comprehensive review of preclinical EGG. Our group recently set up and worked out the methods for EGG in experimental pigs. We gained our initial experience in the use of EGG in assessment of porcine gastric myoelectric activity after volume challenge and after intragastric administration of itopride and erythromycin. The mean dominant frequency in pigs is comparable with that found in humans. EGG in experimental pigs is feasible. Experimental EGG is an important basis for further preclinical projects in pharmacology and toxicology.
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18
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Marquard J, El Scheich T, Klee D, Schmitt M, Meissner T, Mayatepek E, Oh J. Chronic pancreatitis in branched-chain organic acidurias--a case of methylmalonic aciduria and an overview of the literature. Eur J Pediatr 2011; 170:241-5. [PMID: 20924605 DOI: 10.1007/s00431-010-1313-5] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2010] [Accepted: 09/22/2010] [Indexed: 11/27/2022]
Abstract
A severe rare complication in patients with branched-chain organic acidurias (BCOA) is pancreatitis with a limited number of patients published so far. Here, we report on a patient with methylmalonic aciduria (MMA) who developed chronic pancreatitis after several episodes of acute pancreatitis. In addition, an overview is given about some previous published cases with BCOA who developed pancreatitis in the course of the disease. In half of the published MMA patients with pancreatitis, an acute pancreatitis was reported while the rest suffered from a chronic form of this disease. Acute pancreatitis in BCOA patients can clinically present in the context of recurrent vomiting and an impaired general physical condition even without typical signs of pancreatitis. Any form of pancreatitis should be ruled out in the assessment of acutely ill patients with BCOA.
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Affiliation(s)
- Jan Marquard
- Department of General Pediatrics, University Children's Hospital Düsseldorf, Moorenstr 5, 40225 Düsseldorf, Germany.
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19
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Mansi Y, Abdelaziz N, Ezzeldin Z, Ibrahim R. Randomized controlled trial of a high dose of oral erythromycin for the treatment of feeding intolerance in preterm infants. Neonatology 2011; 100:290-4. [PMID: 21701222 DOI: 10.1159/000327536] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2010] [Accepted: 03/09/2011] [Indexed: 11/19/2022]
Abstract
OBJECTIVES To evaluate the effectiveness of high-dose erythromycin to treat feeding intolerance in preterm infants predominantly fed milk formula. DESIGN This study is a prospective randomized controlled trial on 60 premature infants suffering from feeding intolerance. Thirty infants were given oral erythromycin ethylsuccinate at a dose of 50 mg/kg/day for 10 days or until they reached full enteral feeds. Randomization was stratified according to gestational age <32 weeks or ≥32 weeks gestation. The primary end point was the time taken to establish full enteral feeding since enrollment. Potential adverse effects associated with erythromycin were also monitored. Student's t test was used for comparison of continuous variables and χ(2)for categorical data. RESULTS In infants <32 weeks, the use of erythromycin was associated with more daily weight gain (12.8 ± 2.6 g vs. 9.2 ± 5.3 g, p = 0.04) compared to the control group. Time to reach full feed did not differ between the erythromycin (13.8 ± 3.9 days) and the control (17.46 ± 4.9 days) groups (p = 0.07). In infants ≥32 weeks, there were no differences between the erythromycin and the control groups. CONCLUSION High-dose erythromycin is associated with greater weight gain in preterm infants <32 weeks gestational age, who are predominantly fed cow's milk-based protein formulas.
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Affiliation(s)
- Yasmeen Mansi
- Department of Pediatrics, Faculty of Medicine, University of Cairo, Cairo, Egypt.
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20
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Razzaq A, Safdar CA, Ali S. Erythromycin establishes early oral feeding in neonates operated for congenital intestinal atresias. Pediatr Surg Int 2009; 25:361-4. [PMID: 19290531 DOI: 10.1007/s00383-009-2347-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/27/2009] [Indexed: 12/17/2022]
Abstract
PURPOSE The recovery of gastrointestinal function following surgery for congenital intestinal atresias can be prolonged and may increase morbidity and hospital stay. This study was conducted to investigate the prokinetic effect of erythromycin in neonates undergoing surgery for small bowel atresias. METHODS A randomized-controlled trial was conducted at the Departments of Paediatrics and Paediatric Surgery, Military Hospital, Rawalpindi, Pakistan, from January to December 2007 to study the prokinetic effect of erythromycin (3 mg/kg per dose 4 times daily). Thirty consecutive neonates undergoing primary anastomosis for congenital small bowel atresias were randomly divided into two groups: group I (erythromycin) and group II (control). The groups were similar in terms of gestational age, sex, mode of delivery, birth weight and types of atresias. Postoperative recovery of intestinal functions was measured as time taken to achieve full enteral feed (150 ml/kg per 24 h), duration of total parenteral nutrition (TPN) and hospital stay. RESULTS Neonates receiving oral erythromycin achieved full enteral feeding early (13.07 vs. 16.13 days) required TPN for shorter duration (10.53 vs. 13.73 days) and their hospital stay was less (16.2 vs. 18.0 days) as compared to the neonates in the control group who did not receive any erythromycin. The differences were statistically significant. CONCLUSION The administration of oral erythromycin following primary anastomosis for small intestinal atresias results in early recovery of intestinal function, fewer days on TPN and a trend for shorter hospital stay.
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Affiliation(s)
- Asma Razzaq
- Department of Paediatrics, Military Hospital, Rawalpindi, Pakistan
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21
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Venkatasubramani N, Rudolph CD, Sood MR. Erythromycin lacks colon prokinetic effect in children with functional gastrointestinal disorders: a retrospective study. BMC Gastroenterol 2008; 8:38. [PMID: 18718006 PMCID: PMC2529327 DOI: 10.1186/1471-230x-8-38] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2007] [Accepted: 08/21/2008] [Indexed: 11/17/2022] Open
Abstract
Background Motilin, a peptide hormone has a direct excitatory effect on circular smooth muscle strips derived from the human colon. Reduced plasma motilin concentration has been reported in adults with chronic constipation. Erythromycin, a non-peptide motilin receptor agonist, induces phase 3 of the migrating motor complex (MMC) in the antro-duodenum and also reduces oro-cecal transit time. A pediatric study has reported an improvement in clinical symptoms of constipation following erythromycin administration, but the effect on colon motility in children has not been formally evaluated. We used colon manometry to study the effect of intravenous erythromycin lactobionate at 1 mg/kg on colon motiltiy in ten children. Methods We selected patients with normal antroduodenal and colon manometry studies that were performed simultaneously. All studies were performed for clinically indicated reasons. We quantified the effect of erythromycin on colon contraction by calculating the area under the curve (AUC). Results The mean (SE of mean) AUC in the colon during the fasting, post-erythromycin and postprandial phases of the study was 2.1 mmHg/sec (0.35), 0.99 mmHg/sec (0.17) and 3.05 mmHg/sec (0.70) respectively. The AUC following erythromycin was significantly less compared to the fasting phase of the study (p < 0.01). Conclusion Erythromycin lacks colon prokinetic effect in children with chronic constipation evaluated by colon manometry.
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Affiliation(s)
- Narayanan Venkatasubramani
- Division of Pediatric Gastroenterology and Nutrition, The Children's Hospital of Wisconsin and The Medical College of Wisconsin, Milwaukee, WI 53226, USA.
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22
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Nguyen NQ, Chapman M, Fraser RJ, Bryant LK, Burgstad C, Holloway RH. Prokinetic therapy for feed intolerance in critical illness: one drug or two? Crit Care Med 2008; 35:2561-7. [PMID: 17828038 DOI: 10.1097/01.ccm.0000286397.04815.b1] [Citation(s) in RCA: 97] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
OBJECTIVE To compare the efficacy of combination therapy, with erythromycin and metoclopramide, to erythromycin alone in the treatment of feed intolerance in critically ill patients. DESIGN Randomized, controlled, double-blind trial. SETTING Mixed medical and surgical intensive care unit. PATIENTS Seventy-five mechanically ventilated, medical patients with feed intolerance (gastric residual volume > or =250 mL). INTERVENTIONS Patients received either combination therapy (n = 37; 200 mg of intravenous erythromycin twice daily + 10 mg of intravenous metoclopramide four times daily) or erythromycin alone (n = 38; 200 mg of intravenous erythromycin twice daily) in a prospective, randomized fashion. Gastric feeding was re-commenced and 6-hourly gastric aspirates performed. Patients were studied for 7 days. Successful feeding was defined as a gastric residual volume <250 mL with the feeding rate > or =40 mL/hr, over 7 days. Secondary outcomes included daily caloric intake, vomiting, postpyloric feeding, length of stay, and mortality. MEASUREMENTS AND MAIN RESULTS Demographic data; use of inotropes, opioids, or benzodiazepines; and pretreatment gastric residual volume were similar between the two groups. The gastric residual volume was significantly lower after 24 hrs of treatment with combination therapy, compared with erythromycin alone (136 +/- 23 mL vs. 293 +/- 45 mL, p = .04). Over the 7 days, patients treated with combination therapy had greater feeding success, received more daily calories, and had a lower requirement for postpyloric feeding, compared with erythromycin alone. Tachyphylaxis occurred in both groups but was less with combination therapy. Sedation, higher pretreatment gastric residual volume, and hypoalbuminemia were significantly associated with a poor response. There was no difference in the length of hospital stay or mortality rate between the groups. Watery diarrhea was more common with combination therapy (20 of 37 vs. 10 of 38, p = .01) but was not associated with enteric infections, including Clostridium difficile. CONCLUSIONS In critically ill patients with feed intolerance, combination therapy with erythromycin and metoclopramide is more effective than erythromycin alone in improving the delivery of nasogastric nutrition and should be considered as the first-line treatment.
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Affiliation(s)
- Nam Q Nguyen
- Department of Gastroenterology and Hepatology, University of Adelaide, Royal Adelaide Hospital, South Australia.
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23
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Perez ME, Youssef NN. Dyspepsia in childhood and adolescence: insights and treatment considerations. Curr Gastroenterol Rep 2007; 9:447-55. [PMID: 18377794 DOI: 10.1007/s11894-007-0058-4] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/26/2023]
Abstract
Functional dyspepsia (FD) is common in children, with as many as 80% of those being evaluated for chronic abdominal pain reporting symptoms of epigastric discomfort, nausea, or fullness. It is known that patients with persistent complaints have increased comorbidities such as depression and anxiety. The interaction with psychopathologic variables has been found to mediate the association between upper abdominal pain and gastric hypersensitivity. These observations suggest that abnormal central nervous system processing of gastric stimuli may be a relevant pathophysiologic mechanism in FD. Despite increased understanding, no specific therapy has emerged; however, recent nonpharmacological-based options such as hypnosis may be effective. Novel approaches, including dietary manipulation and use of nutraceuticals such as ginger and Iberogast (Medical Futures Inc., Ontario, Canada), may also be considered.
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Affiliation(s)
- Maria E Perez
- Center for Pediatric Irritable Bowel and Motility Disorders, Goryeb Children's Hospital at Atlantic Health, 100 Madison Avenue, Internal Box 82, Morristown, NJ 07962, USA
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24
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Abstract
Chronic functional constipation is a common problem in childhood, with soiling a significant issue. The morbidity is high and the treatment is complex. There is a very poor evidence base for the drug treatments used and there are considerable differences in practice in different units. The key to successful management is early diagnosis and prompt treatment with an emphasis on holistic care with multidisciplinary support where needed. For example, the practical approach in our unit at the Southampton General Hospital, Southampton, England emphasizes the non-drug aspects including patient education and behavioral modification and uses stimulant laxatives, usually in a high dose as first-line therapy. There is an urgent need for prospective comparative studies to investigate different treatment regimens and for longitudinal studies to examine the long-term outcome of chronic constipation and the factors that determine it. The lack of a significant evidence base for the use of the most widely used agents proves a significant challenge in the production of evidence-based guidelines and highlights the paucity of data for most of the widely used treatments for childhood constipation.
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Affiliation(s)
- Adrian Plunkett
- Paediatric Medical Unit, Southampton General Hospital, Southampton, UK
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25
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Jiang DP, Li ZZ, Guan SY, Zhang YB. Treatment of pediatric Ogilvie’s syndrome with low-dose erythromycin: A case report. World J Gastroenterol 2007; 13:2002-3. [PMID: 17461506 PMCID: PMC4146982 DOI: 10.3748/wjg.v13.i13.2002] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Acute colonic pseudo-obstruction is a poorly understood syndrome, characterized by the signs, symptoms and radiological pattern of a large bowel obstruction without evidence for a mechanical obstruction. We report a case of a 2-year old boy who presented with progressive abdominal distention, vomiting and abdominal pain on postoperative d 3. Plain abdominal Χ-ray showed markedly dilated large bowel. Mechanical colonic obstruction was ruled out with hypaque enema. Ogilvie’s syndrome was suspected. The patient received treatment with oral erythromycin which had an immediate beneficial effect. During the 6 mo follow-up, no recurrences of symptoms were observed. We provide a safe and effective therapy for Ogilvie’s syndrome in pediatric individuals.
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Affiliation(s)
- Da-Peng Jiang
- Department of Pediatric Surgery, Second Affiliated Hospital of Harbin Medical University, #246 Xuefu Road, Harbin 150086, Heilongjiang Province, China.
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26
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Lobe TE. The current role of laparoscopic surgery for gastroesophageal reflux disease in infants and children. Surg Endosc 2007; 21:167-74. [PMID: 17200908 DOI: 10.1007/s00464-006-0238-6] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2006] [Accepted: 04/06/2006] [Indexed: 12/15/2022]
Abstract
BACKGROUND The benefits of surgery for gastroesophageal reflux disease (GERD) in infants and children have been questioned in the recent literature. The goal of this review was to determine the best current practice for the diagnosis and management of this disease. METHODS The literature was reviewed for all recent English language publications on the management of GERD in 8- to 10-year-old patients. RESULTS In infants and children, GERD has multiple etiologies, and an understanding of these is important for determining which patients are the best surgical candidates. Proton pump inhibitors (PPIs) have become the mainstay of current treatment for primary GERD. Although laparoscopic surgery appears to be better than open surgery, there remains some morbidity and complications that careful patient selection can minimize. CONCLUSION Surgery for GERD should be performed only after failure of medical management or for specific problems that mandate it.
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Affiliation(s)
- T E Lobe
- University of Tennessee Health Science Center, Memphis, TN, USA.
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27
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Nuntnarumit P, Kiatchoosakun P, Tantiprapa W, Boonkasidecha S. Efficacy of oral erythromycin for treatment of feeding intolerance in preterm infants. J Pediatr 2006; 148:600-5. [PMID: 16737869 DOI: 10.1016/j.jpeds.2005.12.026] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2005] [Revised: 11/03/2005] [Accepted: 12/07/2005] [Indexed: 11/26/2022]
Abstract
OBJECTIVE To determine the efficacy and safety of oral erythromycin (EM) for feeding intolerance in preterm infants < 35 weeks gestation. STUDY DESIGN In this randomized, double-blinded, placebo-controlled trial, preterm infants with feeding intolerance were randomly allocated to a treatment group given EM ethyl succinate 10 mg/kg every 6 hours for 2 days, followed by 4 mg/kg every 6 hours for another 5 days, or to a control group given placebo. The primary outcome was time to full feeding (150 mL/kg/day) after the start of treatment. RESULTS Each group comprised 23 preterm infants, almost all of whom were < 32 weeks gestation. Baseline characteristics were similar between the 2 groups. Times to full feeding were significantly shorter and the number of withheld feeds were significantly less in the EM group than the control group; the respective medians (interquartile ranges) were 7 days (6 to 9 days) versus 13 days (9 to 15 days) (P < .001) and 1 episode (0 to 2 episodes) versus 9 episodes (2 to 13 episodes) (P < .001). No significant differences in episodes of sepsis, necrotizing enterocolitis, and cholestasis were observed. CONCLUSIONS Oral EM was effective and safe for treatment of feeding intolerance in preterm infants.
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Affiliation(s)
- Pracha Nuntnarumit
- Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
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28
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Abstract
Enteral feeding is desirable when the gastrointestinal tract is functional because it allows better use of nutrients, is safer, and is more cost-effective than parenteral nutrition. Feeding through a gastric tube, however, is often not feasible in severely ill adults and children because of gastric paresis leading to recurrent episodes of gastroesophageal reflux with the risk of subsequent aspiration. Feeding into the small intestine (duodenum or jejunum) through a nasointestinal tube, therefore, is preferred. Unfortunately, no method of enteral feeding is risk free. This literature review addresses the following 10 topics: (a) the reasons why nasointestinal tube feeding is better tolerated by some patients, (b) candidates for nasointestinal tube feeding, (c) options for selecting nasointestinal tubes, (d) recommended methods for predicting the distance to insert nasointestinal tubes, (e) recommended methods for placing nasointestinal tubes, (f) how promotility medications work and whether they facilitate nasointestinal tube placement, (g) nasointestinal tube placement error rate, (h) methods of determining the internal location of nasointestinal tubes, (i) complications associated with nasointestinal tube use, and (j) other pertinent issues surrounding feeding through nasointestinal tubes. The available research evidence is summarized and recommendations for future work are suggested.
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Abstract
Gastro-oesophageal reflux (GOR) and gastro-oesophageal reflux disease (GORD) occur frequently during the first months of life. Gastro-oesophageal reflux may be a primary gastro-intestinal motility disorder, but it may also be secondary to other conditions such as cow's milk protein allergy. Objective diagnosis can be difficult because there may be absence of correlation between history, results of pH monitoring and histology. Severe GORD may cause minor symptoms, and minor GOR may cause severe symptoms. Several different therapeutic interventions exist. Simply stated, thickened formula reduces regurgitation and alginates and proton pump inhibitors can be used to decrease acid GOR, depending on the severity of the GORD. Efficacy data of prokinetic drugs are either lacking or disappointing. Regarding side-effects, interest has been focused on cisapride, although other molecules have similar effects. Long-term side-effects such as the nutritional consequence of therapeutic management have been insufficiently studied, especially for the acid-reducing molecules.
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Affiliation(s)
- Yvan Vandenplas
- Academisch Ziekenhuis Vrije Universiteit Brussel, Brussels, Belgium.
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30
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Chicella MF, Batres LA, Heesters MS, Dice JE. Prokinetic drug therapy in children: a review of current options. Ann Pharmacother 2005; 39:706-11. [PMID: 15755792 DOI: 10.1345/aph.1e411] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
OBJECTIVE To review the pharmacology, safety, and efficacy of the prokinetic agents metoclopramide and erythromycin in children. DATA SOURCES English-language literature was accessed using MEDLINE (1970-June 2004) with metoclopramide, erythromycin, macrolides, gastroesophageal reflux, and gastrointestinal motility as the search terms. STUDY SELECTION AND DATA EXTRACTION Abstracts and original research articles were included. Preference was given to published controlled trials. Articles providing descriptions of pharmacology, safety, and effectiveness of metoclopramide and erythromycin for the treatment of gastroesophageal reflux (GER) were also used in this review. DATA SYNTHESIS Some authors advocate using a prokinetic agent along with acid suppression for treatment of GER in children. The 2 prokinetic agents most commonly used are erythromycin and metoclopramide. Erythromycin has numerous observational reports and controlled trials demonstrating its efficacy in improving feeding tolerance in children. Adverse drug reactions associated with its use were uncommon in prospective controlled trials. Few data support the use of metoclopramide for management of GER, and the potential adverse effects associated with its use need to be considered before prescribing. CONCLUSIONS The literature supports the use of erythromycin as a prokinetic agent. Many children with GER are adequately controlled with acid suppression alone; however, if use of a prokinetic agent is warranted, erythromycin in combination with acid suppression should be considered. Given the lack of prospective controlled studies demonstrating metoclopramide's efficacy and safety in the treatment of GER in children, metoclopramide should not be considered a treatment option.
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Affiliation(s)
- Michael F Chicella
- Department of Pharmacy, Children's Hospital of The King's Daughters, Norfolk, VA 23507-1910, USA.
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31
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Zanolari P, Steiner A, Meylan M. Effects of Erythromycin on Myoelectric Activity of the Spiral Colon of Dairy Cows. ACTA ACUST UNITED AC 2004; 51:456-61. [PMID: 15610492 DOI: 10.1111/j.1439-0442.2004.00672.x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
The effects of erythromycin on myoelectric activity of the spiral colon of dairy cows were investigated in a prospective study. Four Simmental x Red-Holstein crossbred cows of similar body weight and condition with seven pairs of bipolar electrodes implanted in the intestine (one each in the distal ileum, caecum and proximal colon, and four in the spiral colon) were included. Erythromycin lactobionate (1 mg kg(-1)) and 0.9% sodium chloride solution (NaCl) were administered to each cow in a random order. Erythromycin was diluted with NaCl and both treatments were administered slowly intravenously over a period of 5 min 1 h after onset of a phase III of the bovine colonic migrating myoelectric complex (bcMMC). A 3-6-day washout period was scheduled between trials. Significant differences between the results of the treatments were observed for spike duration in phase I as well as for spike duration and duration of spiking activity during phase II of the second bcMMC, which were significantly higher after erythromycin treatment than after NaCl. These findings suggest an indirect effect of erythromycin on colonic motility in cattle.
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Affiliation(s)
- P Zanolari
- Clinic for Ruminants, Vetsuisse-Faculty of Berne, Bremgartenstrasse 109a, PO Box 8466, 3001 Berne, Switzerland.
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Curry JI, Lander AD, Stringer MD. A multicenter, randomized, double-blind, placebo-controlled trial of the prokinetic agent erythromycin in the postoperative recovery of infants with gastroschisis. J Pediatr Surg 2004; 39:565-9. [PMID: 15065029 DOI: 10.1016/j.jpedsurg.2003.12.020] [Citation(s) in RCA: 36] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
BACKGROUND/PURPOSE The recovery of gut function after repair of gastroschisis is frequently prolonged, and these infants are prone to complications associated with parenteral nutrition. This trial was designed to investigate the effect of the prokinetic agent, erythromycin, on the attainment of full enteral feeding in infants after primary repair of uncomplicated gastroschisis. METHODS A multicenter, randomized, double-blind, placebo-controlled trial was used to investigate the effect of enteral erythromycin (3 mg/kg/dose 4 times daily) compared with placebo on the attainment of full enteral feeding tolerance after primary repair of uncomplicated gastroschisis. Eleven neonatal surgical units in the United Kingdom participated in the study. The primary end-point was the time taken to achieve continuous enteral feeding at 150 mL/kg/24 hours sustained for 48 hours. RESULTS Of 70 eligible infants, 62 were recruited and randomly divided. There were 30 patients in group I (placebo) and 32 in group II (erythromycin). The groups were comparable in terms of mean gestational age, mean birth weight, extent of evisceration, and degree of intestinal peel. There was no statistically significant difference between the 2 groups in the time taken to achieve full enteral feeding (27.2 v 28.7 days; P =.75). Similarly, no significant differences were found in the incidence of catheter-related sepsis, duration of parenteral nutrition, or time to discharge between the 2 groups. CONCLUSIONS Enterally administered erythromycin at a dose of 3 mg/kg 4 times daily conferred no advantage in the time taken to achieve full enteral feeding after primary repair of uncomplicated gastroschisis.
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Affiliation(s)
- J I Curry
- Great Ormond Street Hospital for Children, London, England, UK
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Bellomo-Brandão MA, Collares EF, da-Costa-Pinto EAL. Use of erythromycin for the treatment of severe chronic constipation in children. Braz J Med Biol Res 2003; 36:1391-6. [PMID: 14502372 DOI: 10.1590/s0100-879x2003001000016] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
The efficacy of erythromycin was assessed in the treatment of 14 children aged 4 to 13 years with refractory chronic constipation, and presenting megarectum and fecal impaction. A double-blind, placebo- controlled, crossover study was conducted at the Pediatric Gastroenterology Outpatient Clinic of the University Hospital. The patients were randomized to receive placebo for 4 weeks followed by erythromycin estolate, 20 mg kg-1 day-1, divided into four oral doses for another 4 weeks, or vice versa. Patient outcome was assessed according to a clinical score from 12 (most severe clinical condition) to 0 (complete recovery). At enrollment in the study and on the occasion of follow-up medical visits at two-week intervals, patient score and laxative requirements were recorded. During the first 30 days, the mean SD clinical score for the erythromycin group (N = 6) decreased from 8.2+/-2.3 to 2.2+/-1.0 while the score for the placebo group (N = 8) decreased from 7.8+/-2.1 to 2.9+/-2.8. During the second crossover phase, the score for patients on erythromycin ranged from 2.9+/-2.8 to 2.4+/-2.1 and the score for the patients on placebo worsened from 2.2+/-1.0 to 4.3+/-2.3. There was a significant improvement in score when patients were on erythromycin (P < 0.01). Mean laxative requirement was lower when patients ingested erythromycin (P < 0.05). No erythromycin-related side effects occurred. Erythromycin was useful in this group of severely constipated children. A larger trial is needed to fully ascertain the prokinetic efficacy of this drug as an adjunct in the treatment of severe constipation in children.
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Affiliation(s)
- M A Bellomo-Brandão
- Departamento de Pediatria, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP, Brasil
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De Giorgio R, Barbara G, Stanghellini V, Tonini M, Vasina V, Cola B, Corinaldesi R, Biagi G, De Ponti F. Review article: the pharmacological treatment of acute colonic pseudo-obstruction. Aliment Pharmacol Ther 2001; 15:1717-1727. [PMID: 11683685 DOI: 10.1046/j.1365-2036.2001.01088.x] [Citation(s) in RCA: 66] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Acute colonic pseudo-obstruction (Ogilvie's syndrome) can be defined as a clinical condition with symptoms, signs and radiological appearance of acute large bowel obstruction unrelated to any mechanical cause. Recent reports of the efficacy of cholinesterase inhibitors in relieving acute colonic pseudo-obstruction have fuelled interest in the pharmacological treatment of this condition. The aim of the present review is to outline current perspectives in the pharmacological treatment of patients with acute colonic pseudo-obstruction. The best documented pharmacological treatment of Ogilvie's syndrome is intravenous neostigmine (2-2.5 mg), which leads to quick decompression in a significant proportion of patients after a single infusion. However, the search for new colokinetic agents for the treatment of lower gut motor disorders has made available a number of drugs that may also be therapeutic options for Ogilvie's syndrome. Among these agents, the potential of 5-hydroxytryptamine-4 receptor agonists and motilin receptor agonists is discussed.
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Affiliation(s)
- R De Giorgio
- Department of Internal Medicine and Gastroenterology, University of Bologna, Bologna, Italy
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