Zinc supplementation as adjunct therapy in children with measles accompanied by pneumonia: a double-blind, randomized controlled trial. 158 Efficacy of Immnunotherapy with an Oral Bacterial Lysate and Vitamin C in the Primary Prevention of Acute Respiratory Tract Infections in Children Global and regional child mortality and burden of disease attributable to zinc deficiency Respiratory infections reduce the growth response to vitamin A supplementation in a randomized controlled trial. A randomized trial of vitamin A supplements in relation to mortality among human immunodeficiency virus-infected and uninfected children in Tanzania. Vitamin D3 supplementation in patients with frequent respiratory tract infections: a randomised and double-blind intervention study Maternal vitamin D supplementation during pregnancy and lactation to prevent acute respiratory infections in infancy in Dhaka, Bangladesh (MDARI trial): protocol for a prospective cohort study nested within a randomized controlled trial Adverse effects of high-dose vitamin A supplements in children hospitalized with pneumonia. Randomized, double-blind, placebo-controlled clinical trial of the efficacy of treatment with zinc or vitamin A in infants and young children with severe acute lower respiratory infection. Vitamin A supplements and diarrheal and respiratory tract infections among children in Dar es Salaam, Tanzania. Micronutrients as adjunct therapy of acute illness in children: impact on the episode outcome and policy implications of current findings. Vitamin A supplementation and severity of pneumonia in children admitted to the hospital in Dar es Salaam, Tanzania. A randomized controlled trial of vitamin D3 supplementation for the prevention of symptomatic upper respiratory tract infections. Effect of weekly zinc supplements on incidence of pneumonia and diarrhoea in children younger than 2 years in an urban, low-income population in Bangladesh: randomised controlled trial Appropriate Antibiotic Use for Acute Respiratory Tract Infection in Adults: Advice for High-Value Care From the American College of Physicians and the Centers for Disease Control and Prevention Vitamin A supplements ameliorate the adverse effect of HIV-1, malaria, and diarrheal infections on child growth. Impact of trace elements and vitamin supplementation on immunity and infections in institutionalized elderly patients: a randomized controlled trial. MIN. VIT. AOX. geriatric network. Effect of vitamin A supplementation on morbidity of low-birth-weight neonates. Vitamin A supplementation at birth delays pneumococcal colonization in South Indian infants. Principles of Appropriate Antibiotic Use for Treatment of Acute Respiratory Tract Infections in Adults: Background, Specific Aims, and Methods Vitamin A supplementation fails to reduce incidence of acute respiratory illness and diarrhea in preschool-age Indonesian children. Randomised, double blind, placebo controlled clinical trial of efficacy of vitamin A treatment in non-measles childhood pneumonia Multiple micronutrient supplementation in Tanzanian infants born to HIV-infected mothers: a randomized, double-blind, placebo-controlled clinical trial.
BACKGROUND Zinc deficiency , common in developing countries , is associated with decreased immunocompetence . Zinc supplementation  benefits children with acute and persistent diarrhea and prevents pneumonia . Most deaths from vaccine-preventable diseases are from measles and whooping cough ; pneumonia is the most common complication of measles and often the proximate cause of related deaths . OBJECTIVE We evaluated the effect of zinc supplementation on episodes of illness in children with measles accompanied by pneumonia . DESIGN In a double-blind , r and omized controlled trial , children aged 9 mo-15 y who were admitted to the Infectious Diseases Hospital in Calcutta with clinical ly severe measles accompanied by pneumonia and who had been ill for < /= 7 d were r and omly assigned to receive zinc ( 20 mg , in elemental form as acetate , twice daily for 6 d ) or a placebo . All patients received st and ard treatment with antibiotics and an initial 100 000-IU dose of vitamin A ( as palmitate ) by mouth . RESULTS Time-to-event analysis using the Cox proportional hazards model ( 42 in the zinc group and 43 in the placebo group ) showed that the time needed for the resolution of fever and tachypnea , the return of appetite , and the achievement of a " much improved " or " cured " status was not different between the 2 groups . A high proportion of children had low serum retinol and zinc concentrations . Improvement in serum zinc and retinol concentrations after 6 d of treatment was not different between the 2 groups . CONCLUSION Children with severe measles accompanied by pneumonia treated with antibiotics and vitamin A did not show any additional benefit from also receiving a zinc supplement Background Airway infections are of great importance worldwide and nearly half of the pediatric consultations in industrialized countries are caused by respiratory tract infections ( RTIs ) . Acute respiratory tract infections ( ARTIs ) are among the main causes of morbidity and mortality in children and recurrent infections of the respiratory tract are the most frequent cause of pharmacotherapy in pediatric practice . The aim of this study was to evaluate the efficacy and tolerability of immunotherapy with oral bacterial lysates + vitamin C in the prevention of ARTIs in children . Methods 109 children with ages between 4 and 16 years with frequent respiratory tract infections ( 2–5 infections the previous winter ) were evaluated . Participants were r and omly allocated in 2 groups : 52 patients ( mean age 6.8 ± 2.9 years ; 20 males 32 females ) received no preventive therapy ( NPT group ) and 57 ( mean age 9.0 ± 3.3 years ; males 36 females 21 ) received immunotherapy with oral bacterial lysates + vitamin C ( VC group ) at the recommended dosage . Patients were followed up for 6 months , including the administration period . Primary end points were the type and number of ARTIs . Secondary end points ( after the infection occured ) included : time to clinical cure , severity of infection , absenteeism from school due to an ARTI , number of antibiotic courses or other drugs prescribed , and duration of concomitant drug treatment . Results There were significant differences between groups in the cumulative number of acute infectious episodes : 170 in NPT group ( 141 upper ARTIs , 29 lower ARTI , and 26 otitis episodes ) vs 55 in VC group ( 50 upper ARTIs , 5 lower ARTI and 4 otitis episodes ) . Patients in the NPT group received 127 antibiotic courses compared to 28 in the VC group ( P < 0.0001 ) . Patients in the NPT group had 475 days of absenteeism from school compared to 100 days in the VC group ( P < 0.0001 ) . No adverse events related to the trial medications were reported . Conclusions Immunotherapy with oral bacterial lysates and vitamin C appears to be very effective in the prevention of infectious episodes in pediatric patients with frequent respiratory tract infections . Future studies are needed to further explore the role of oral bacteroial lysates in ARTIs prevention Background / Objectives : Zinc is an essential micronutrient and deficiency can lead to an increased risk for infectious diseases and growth retardation among children under 5 years of age . We aim ed to estimate disease-specific and all-cause mortality attributable to zinc deficiency . Subject/ Methods : We estimated the prevalence of zinc deficiency in Latin America , Africa and Asia , where based on zinc availability in the diet and childhood stunting rates , zinc deficiency is widespread . The relative risks of death among zinc-deficient children for diarrhea , malaria and pneumonia were estimated from r and omized controlled trials . We used the comparative risk assessment methods to calculate deaths and burden of disease ( measured in disability-adjusted life years , DALYs ) from each of these three diseases attributable to zinc deficiency in these regions . Results : Zinc deficiency was responsible for 453 207 deaths ( 4.4 % of childhood deaths ) , and 1.2 % of the burden of disease ( 3.8 % among children between 6 months and 5 years ) in these three regions in 2004 . Of these deaths , 260 502 were in Africa , 182 546 in Asia and 10 159 in Latin America . Zinc deficiency accounted for 14.4 % of diarrhea deaths , 10.4 % of malaria deaths and 6.7 % of pneumonia deaths among children between 6 months and 5 years of age . Conclusions : Zinc deficiency contributes to substantial morbidity and mortality , especially from diarrhea .  Zinc supplementation provided as an adjunct treatment for diarrhea may be the best way to target children most at risk of deficiency BACKGROUND Studies on the effect of vitamin A supplementation on growth have yielded various results . It is possible that such growth is dependent on the burden of infectious diseases in the population . METHODS We analysed data from a r and omized , double-masked , placebo-controled trial to examine the role of respiratory infections and diarrhoea in modifying the growth response to vitamin A supplementation . A single high dose of vitamin A or placebo was given every 4 months to 1405 children aged 6 - 48 months , and 4430 child treatment cycles were used in this analysis . RESULTS Vitamin A supplementation modestly improved linear but not ponderal growth of children who experienced little respiratory infection and especially of those who had vitamin A intake below the normative requirement ( < 400 RE/day ) . Children who received vitamin A and were free of respiratory infection grew 0.22 cm/4 months ( 95 % CI : 0.08 , 0.37 ) more in height than the placebo group , but those with > or = 21.5 % of days of respiratory infection did not show a significant growth response to vitamin A supplementation . Children who experienced no respiratory infection and had vitamin A intake < 400 RE/day benefited most , gaining 0.31 cm/4 months ( 95 % CI : 0.10 , 0.52 ) more in height compared to the placebo group . Diarrhoea was associated with poorer growth , but did not significantly modify the effect of  vitamin A supplementation  on growth . CONCLUSIONS Vitamin A supplementation improves the linear growth of children who have a low intake of vitamin A but this impact is muted with increasing levels of respiratory infections OBJECTIVES To determine whether vitamin A supplements result in reduced mortality among HIV-infected and uninfected children . DESIGN R and omized , double blind , placebo-controlled trial . METHODS Starting in April , 1993 , we r and omized 687 children age 6 months to 5 years who were admitted to the hospital with pneumonia . Children who were severely malnourished or had clinical signs of vitamin A deficiency were excluded . At baseline children received placebo or 400 000 IU ( or half that for infants ) of vitamin A , in addition to st and ard treatment for pneumonia . They received further doses of the same regimen 4 and 8 months after hospital discharge . Sera from children were tested for HIV antibodies by enzyme-linked immunosorbent assay and Western blot tests . For positive children < 15 months of age , HIV infection was confirmed by amplified heat-denatured HIV-p24 antigen assays with confirmatory neutralization assays . HIV status was ascertained for 648 of 687 enrolled children . The mean duration of follow-up was 24.4 months ( SD = 12.1 ) . RESULTS Of 648 children 58 ( 9 % ) were HIV-infected . Compared with uninfected children , all-cause mortality was higher among HIV-infected children , as was mortality caused by pneumonia or diarrhea ( P < 0.001 for each ) . Overall vitamin A supplements result ed in a 49 % reduction in mortality [ relative risk ( RR ) , 0.51 ; 95 % confidence interval ( CI ) , 0.29 to 0.90 , P = 0.02 ] . Vitamin A supplements reduced all-cause mortality by 63 % among HIV-infected children ( RR 0.37 ; CI 0.14 to 0.95 , P = 0.04 ) and by 42 % among uninfected children ( RR 0.58 , CI 0.28 to 1.19 , P = 0.14 ) . Vitamin A supplements were also associated with a 68 % reduction in AIDS-related deaths ( P = 0.05 ) and a 92 % reduction in diarrhea-related deaths ( P = 0.01 ) . CONCLUSION Vitamin A deficiency , which is common among children in many developing countries , is particularly severe among HIV-infected children . Our findings indicate that vitamin A supplements , a low cost intervention , reduce mortality of HIV-infected children Background Low serum levels of 25-hydroxyvitamin D3 are associated with an increased risk of respiratory tract infections ( RTIs ) . Clinical trials with vitamin D3 against various infections have been carried out but data are so far not conclusive . Thus , there is a need for additional r and omised controlled trials of effects of vitamin D3 on infections . Objective To investigate if supplementation with vitamin D3 could reduce infectious symptoms and antibiotic consumption among patients with antibody deficiency or frequent RTIs . Design A double-blind r and omised controlled trial . Setting Karolinska University Hospital , Huddinge . Participants 140 patients with antibody deficiency ( selective IgA subclass deficiency , IgG subclass deficiency , common variable immune disorder ) and patients with increased susceptibility to RTIs ( > 4 bacterial RTIs/year ) but without immunological diagnosis . Intervention Vitamin D3 ( 4000 IU ) or placebo was given daily for 1 year . Primary and secondary outcome measures The primary endpoint was an infectious score based on five parameters : symptoms from respiratory tract , ears and sinuses , malaise and antibiotic consumption . Secondary endpoints were serum levels of 25-hydroxyvitamin D3 , microbiological findings and levels of antimicrobial peptides ( LL-37 , HNP1–3 ) in nasal fluid . Results The overall infectious score was significantly reduced for patients allocated to the vitamin D group ( 202 points ) compared with the placebo group ( 249 points ; adjusted relative score 0.771 , 95 % CI 0.604 to 0.985 , p=0.04 ) . Limitations A single study centre , small sample size and a selected group of patients . The sample size calculation was performed using p=0.02 as the significance level whereas the primary and secondary endpoints were analysed using the conventional p=0.05 as the significance level . Conclusions Supplementation with vitamin D3 may reduce disease burden in patients with frequent RTIs Background Early infancy is a high-risk period for severe acute respiratory infection ( ARI ) , particularly in low-income countries with re source -limited health systems . Lower respiratory tract infection ( LRTI ) is commonly preceded by upper respiratory infection ( URTI ) , and often caused by respiratory syncytial virus ( RSV ) , influenza and other common community-acquired viral pathogens . Vitamin D status is a c and i date modifiable early-life determinant of the host antiviral immune response and thus may influence the risk of ARI-associated morbidity in high-risk population s. Methods / Design In the Maternal Vitamin D for Infant Growth ( MDIG ) study in Dhaka , Bangladesh ( NCT01924013 ) , 1300 pregnant women are r and omized to one of five groups : placebo , 4200 IU/week , 16,800 IU/week , or 28,000 IU/week from 2nd trimester to delivery plus placebo from 0–6 months postpartum ; or , 28,000 IU/week prenatal and until 6-months postpartum . In the Maternal Vitamin D for ARI in Infancy ( MDARI ) sub- study nested within the MDIG trial , trained personnel conduct weekly postnatal home visits to inquire about ARI symptoms and conduct a st and ardized clinical assessment . Supplementary home visits between surveillance visits are conducted when caregivers make phone notifications of new infant symptoms . Mid-turbinate nasal swab sample s are obtained from infants who meet st and ardized clinical ARI criteria . Specimens are tested by polymerase chain reaction ( PCR ) for 8 viruses ( influenza A/B , parainfluenza 1/2/3 , RSV , adenovirus , and human metapneumovirus ) , and nasal carriage density of Streptococcus pneumoniae . The primary outcome is the incidence rate of microbiologically-positive viral ARI , using incidence rate ratios to estimate between-group differences . We hypothesize that among infants 0–6 months of age , the incidence of microbiologically-confirmed viral ARI will be significantly lower in infants whose mothers received high-dose prenatal/postpartum vitamin D supplements versus placebo . Secondary outcomes include incidence of ARI associated with specific pathogens ( influenza A or B , RSV ) , clinical ARI , and density of pneumococcal carriage . Discussion If shown to reduce the risk of viral ARI in infancy , integration of maternal prenatal/postpartum vitamin D supplementation into antenatal care programs in South Asia may be a feasible primary preventive strategy to reduce the burden of ARI-associated morbidity and mortality in young infants . Trial registration NCT02388516 , registered March 9 , 2015 OBJECTIVE To test the hypothesis that high-dose vitamin A supplements will enhance recovery of children hospitalized for the treatment of community-acquired pneumonia . DESIGN We conducted a r and omized , double-blind , placebo-controlled clinical trial of high-dose vitamin A supplements among children 3 months to 10 years of age ( N = 95 ) admitted to hospital with community-acquired pneumonia in Lima , Peru . Children < /=1 year of age received 100 000 IU of water-miscible vitamin A on admission to the hospital and an additional 50 000 IU the next day . Children > 1 year of age received 200 000 IU on admission and 100 000 IU the next day . RESULTS Children receiving vitamin A ( n = 48 ) had lower blood oxygen saturation ( the mean difference on day 3 in hospital was 1.1 % ) , higher prevalence rates of retractions ( 37 % in the vitamin A group vs 15 % in the placebo group on day 3 ) , auscultatory evidence of consolidation ( 28 % in the vitamin A group vs 17 % in the placebo group on day 3 ) , and were more likely to require supplemental oxygen ( 21 % in the vitamin A group vs 8 % in the placebo group on day 3 ) than children in the placebo group ( n = 47 ) . Adjustment for baseline severity of disease and nutritional status did not alter the association of vitamin A with increased clinical severity , although the difference in blood oxygen saturation was no longer statistically significant . No differences were seen in duration of hospitalization or in chest x-ray changes 14 days after admission . No deaths occurred , and toxicity of vitamin A was not seen . CONCLUSIONS This study indicates that high-dose vitamin A supplements cause modest adverse effects in children recovering from pneumonia and should not be used therapeutically in such patients unless there is clinical evidence of vitamin A deficiency or concurrent measles infection BACKGROUND Acute lower respiratory infection ( ALRI ) is a leading cause of childhood death . Zinc supplementation prevents ALRI . Vitamin A supplementation reduces childhood mortality , but its benefit concerning ALRI-specific mortality is unproven . OBJECTIVE The objective was to evaluate the effect of zinc and vitamin A on the clinical recovery of children with severe ALRI . DESIGN In a controlled trial with a factorial design , 153 children aged 2 - 24 mo who were hospitalized with severe ALRI were r and omly assigned to receive 10 mg zinc as acetate ( twice daily for 5 d ) plus vitamin A placebo , 10 000 micro g retinol equivalents vitamin A ( twice daily for 4 d ) plus zinc placebo , zinc plus vitamin A , or zinc and vitamin A placebos . The main outcome variable was the time for resolution of very ill status ; other outcomes were resolution of fever , tachypnea , and feeding difficulty . RESULTS Recovery rates from very ill status and from fever in zinc-treated boys were 2.6 times ( P = 0.004 ) and 3 times ( P = 0.003 ) those in non-zinc-treated children ; feeding difficulty and tachypnea were not significantly different between groups after an adjusted analysis . Recovery rates were not significantly different between groups on the basis of vitamin A treatment . At discharge , serum zinc was 6.06 micro mol/L higher ( P = 0.001 ) in the zinc-treated children , and serum retinol was 0.387 micro mol/L higher ( P = 0.001 ) in the vitamin A-treated children . CONCLUSION Zinc treatment significantly reduces duration of fever and very ill status in boys , but not in girls , with severe ALRI . Vitamin A treatment of children with severe ALRI had no significant beneficial effect OBJECTIVE To determine the effect of vitamin A supplementation on the  risk of diarrhea and of acute respiratory infection .  DESIGN Double-blind , r and omized , placebo-controlled trial . SETTING Dar-es-Salaam , Tanzania . SUBJECTS Six hundred eighty-seven children , 6 to 60 months old , hospitalized with pneumonia , who received vitamin A or placebo at baseline and at 4 and 8 months after discharge from hospital . MAIN OUTCOME VARIABLES Incidence and duration of episodes of diarrhea and respiratory tract infections during the year after discharge from the hospital . RESULTS Relative to those receiving placebo , children receiving vitamin A had a significantly smaller risk of severe watery diarrhea ( multivariate odds ratio = 0.56 , 95 % CI = 0.32 - 0.99 , P = .04 ) but a higher risk of cough and rapid respiratory rate ( multivariate odds ratio = 1.67 , 95 % CI = 1.17 - 2.36 , P = .004 ) . Vitamin A supplementation was also associated with increased risk of acute diarrhea among normally nourished children or children with stunted growth but was relatively protective among children with wasting disease ( P value for interaction = .01 ) . The apparently increased risk of respiratory tract infection was limited to children who were seronegative for human immunodeficiency virus ( HIV ) ( P value for interaction = .07 ) . CONCLUSIONS Vitamin A supplements provide a low-cost intervention against morbidity in HIV-infected and undernourished children . Supplements may also have serious non-lethal adverse outcomes in well-nourished individuals . Whether these apparent detrimental effects of vitamin A are transient or long-term needs to be examined Role of micronutrients namely vitamin A , zinc and folate , as adjunct therapy of illness episodes in children in developing countries have been discussed in the light of health policy . Apart from a selective review , attempts have been made to statistically combine results of several studies to address policy issues . In children , vitamin A supplementation during illness has ( a ) a profound effect in reducing mortality in measles , ( b ) possibly a significant effect in reducing persistent diarrhea episodes in children with acute diarrhea , and ( c ) no benefit in pneumonia . Use of large dose vitamin A is recommended during measles episodes but not in non-measles pneumonia . Its use in acute diarrhea is debatable but recommended in persistent diarrhea and in severe malnutrition as a component of a micronutrient mixture . Large dose vitamin A supplementation should be used with caution in young infants as there are unresolved concerns about its safety particularly , bulging fontanelle observed in infants when co-administered at immunization . In children , zinc supplementation during illness , ( a ) had a marked effect in reducing prolonged episodes and a modest effect on episode duration in acute diarrhea , ( b ) result ed in reduced rate of treatment failure and death in persistent diarrhea , ( c ) had no effect in measles and non-measles pneumonia , and ( d ) probably had a detrimental effect of increasing death rate when a large dose was used in severely malnourished children . The desirability of routine zinc supplementation therapy of undernourished children with acute diarrhea should be assessed further . Concerning policy , zinc supplementation as a component of a micronutrient mixture is recommended in the rehabilitation of severely malnourished children and in persistent diarrhea . However , recommendation for its routine use in all cases of acute diarrhea in children needs additional studies on effectiveness , cost , operations and safety . In two r and omized controlled trials folate has been evaluated in acute and persistent diarrhea and found to have no beneficial effect . Folate is not recommended as adjunct therapy of diarrhea . Role of folate in preventing severe disease and /or death deserves further evaluation Vitamin A deficiency and acute lower respiratory tract infections coexist as important public health problems in many developing countries . We carried out a r and omized , double-blind , placebo-controlled trial to examine whether large doses of vitamin A given to Tanzanian children who are admitted to the hospital with nonmeasles pneumonia would reduce the severity of respiratory disease .  Six hundred eighty-seven children were r and omly assigned to receive either placebo or vitamin A [ 200 000 IU ( 60 mg retinol equivalents ) for children > 1 y of age and 100000 IU ( 30 mg retinol equivalents ) for infants ] on the day of admission and another dose on the following day . Of the 346 children in the vitamin A group , 13 died in the hospital , compared with 8 of 341 children in the placebo group ; the relative mortality was 1.63 ( 95 % CI : 0.67 , 3.97 ; P = 0.28 ) . The mean number of days of hospitalization was the same in both groups ( 4.2 d ) . There were no differences between the vitamin A and placebo groups in the duration of hospital stay when examined within categories of children stratified by age , sex , breast-feeding status , nutritional status at baseline , or quartile of dietary vitamin A intake in the 4 mo before admission to the hospital . There were also no differences in the mean number of days of fever , rapid respiratory rate , or hypoxia , whether these endpoints were examined in the total number of subjects or in a subset with more severe clinical conditions at baseline . Large doses of vitamin A had no protective effect on the course of pneumonia in hospitalized Tanzanian children Vitamin D has been shown to be an important immune system regulator . Vitamin D insufficiency during winter may cause increased susceptibility to upper respiratory tract infections ( URIs ) . To determine whether vitamin D supplementation during the winter season prevents or decreases URI symptoms , 162 adults were r and omized to receive 50 microg vitamin D3 ( 2000 IU ) daily or matching placebo for 12 weeks . A bi-weekly question naire was used to record the incidence and severity of URI symptoms . There was no difference in the incidence of URIs between the vitamin D and placebo groups ( 48 URIs vs. 50 URIs , respectively , P=0.57 ) . There was no difference in the duration or severity of URI symptoms between the vitamin D and placebo groups [ 5.4+/-4.8 days vs. 5.3+/-3.1 days , respectively , P=0.86 ( 95 % CI for the difference in duration -1.8 to 2.1 ) ] . The mean 25-hydroxyvitamin D level at baseline was similar in both groups ( 64.3+/-25.4 nmol/l in the vitamin D group ; 63.0+/-25.8 nmol/l in the placebo group ; n.s . ) . After 12 weeks , 25-hydroxyvitamin D levels increased significantly to 88.5+/-23.2 nmol/l in the vitamin D group , whereas there was no change in vitamin D levels in the placebo group . There was no benefit of vitamin D3 supplementation in decreasing the incidence or severity of symptomatic URIs during winter . Further studies are needed to determine the role of vitamin D in infection BACKGROUND Pneumonia and diarrhoea cause much morbidity and mortality in children younger than 5 years . Most deaths occur during infancy and in developing countries . Daily regimens of zinc have been reported to prevent acute lower respiratory tract infection and diarrhoea , and to reduce child mortality . We aim ed to examine whether giving zinc weekly could prevent clinical pneumonia and diarrhoea in children younger than 2 years . METHODS 1665 poor , urban children aged 60 days to 12 months were r and omly assigned zinc ( 70 mg ) or placebo orally once weekly for 12 months . Children were assessed every week by field research assistants . Our primary outcomes were the rate of pneumonia and diarrhoea . The rates of other respiratory tract infections were the secondary outcomes . Growth , final serum copper , and final haemoglobin were also measured . Analysis was by intention to treat . FINDINGS 34 children were excluded before r and om assignment to treatment group because they had tuberculosis . 809 children were assigned zinc , and 812 placebo .  After treatment assignment , 103 children in the treatment group and 44 in the control group withdrew . There were significantly fewer incidents of pneumonia in the zinc group than the control group ( 199 vs 286 ; relative risk 0.83 , 95 % CI 0.73 - 0.95 ) , and a small but significant effect on incidence of diarrhoea ( 1881 cases vs 2407 ; 0.94 , 0.88 - 0.99 ) . There were two deaths in the zinc group and 14 in the placebo group ( p=0.013 ) . There were no pneumonia-related deaths in the zinc group , but ten in the placebo group ( p=0.013 ) . The zinc group had a small gain in height , but not weight at 10 months compared with the placebo group . Serum copper and haemoglobin concentrations were not adversely affected after 10 months of zinc supplementation . INTERPRETATION 70 mg of zinc weekly reduces pneumonia and mortality in young children . However , compliance with weekly intake might be problematic outside a research programme Acute respiratory tract infection ( ARTI ) , which includes acute uncomplicated bronchitis , pharyngitis , rhinosinusitis , and the common cold , is the most common reason for acute outpatient physician office visits and antibiotic prescription in adults .  Antibiotics are prescribed at more than 100 million adult ambulatory care visits annually , and 41 % of these prescriptions are for respiratory conditions ( 1 ) . Inappropriate antibiotic use for ARTI is an important contributor to antibiotic resistance , an urgent public health threat ( 2 ) . In the United States , at least 2 million antibiotic-resistant illnesses and 23000 deaths occur each year , at a cost to the U.S. economy of at least $ 30 billion ( 2 ) . Increased community use of antibiotics is highly correlated with emerging antibiotic-resistant infections . In places with greater prescribing of broad-spectrum antibiotics , specifically extended-spectrum cephalosporins and macrolides , rates of multidrug-resistant pneumococcal disease are higher ( 3 ) . Antibiotics are also responsible for the largest number of medication-related adverse events , implicated in 1 of every 5 visits to emergency departments for adverse drug reactions ( 4 ) . Adverse events range in severity from mild ( for example , diarrhea and rash ) to life-threatening ( for example , StevensJohnson syndrome , anaphylaxis , or sudden cardiac death ) . Although data on adverse events after inappropriate antibiotic use are not available , an estimated 5 % to 25 % of patients who use antibiotics have adverse events , and about 1 in 1000 has a serious adverse event ( 2 ) . Clostridium difficile diarrhea , which can be life-threatening and is usually a result of antibiotic treatment , causes nearly 500000 infections and 29300 deaths in the United States each year , leading to an estimated $ 1 billion in extra medical costs ( 5 ) . In 2009 , direct antibiotic prescription costs totaled $ 10.7 billion ; 62 % of these costs ( $ 6.5 billion ) were attributed to antibiotic prescribing in the community setting , followed by $ 3.6 billion in hospitals and $ 527 million in nursing homes and long-term care facilities ( 6 ) . An estimated 50 % of antibiotic prescriptions may be unnecessary or inappropriate in the outpatient setting ( 7 ) ( Unpublished data . Centers for Disease Control and Prevention ) , which equates to more than $ 3 billion in excess costs . Over the past decade , antibiotic prescriptions have decreased by 18 % among persons aged 5 years or older in the United States ; however , prescriptions for  broad-spectrum antibiotics ( fluoroquinolones and macrolides ) have increased by at least 4-fold ( 8) . Reducing inappropriate antibiotic prescribing in the ambulatory setting is a public health priority . This article by the American College of Physicians ( ACP ) and the Centers for Disease Control and Prevention presents available evidence on the appropriate prescribing of antibiotics for adult patients with ARTI . The high-value care advice is intended to amplify rather than replace messages from recent clinical guidelines on appropriate antibiotic prescribing ( 919 ) and serves as an up date of the 2001 Principles of Appropriate Antibiotic Use for Treatment of Acute Respiratory Tract Infections in Adults ( 9 ) and a complement to the pediatric principles published in 2013 ( 20 ) . The target audience for this article is all clinicians providing care to adults seeking ambulatory care for ARTI . Methods We conducted a narrative review of evidence about appropriate antibiotic use for treatment of patients with ARTI syndromes , including acute uncomplicated bronchitis , pharyngitis , rhinosinusitis , and the common cold . We included current clinical guidelines from leading professional societies , such as the Infectious Diseases Society of America ( IDSA ) . Clinical guideline recommendations were augmented with evidence -based meta-analyses , systematic review s , and r and omized clinical trials . To identify these evidence -based articles , we conducted literature search es in the Cochrane Library , PubMed , MEDLINE , and EMBASE through September 2015 . We included only English- language articles and used the following Medical Subject Headings terms : acute bronchitis , respiratory tract infection , pharyngitis , rhinosinusitis , and the common cold . The focus of the article was limited to healthy adults without chronic lung disease ( such as cystic fibrosis , bronchiectasis , and chronic obstructive pulmonary disease ) or immunocompromising conditions ( congenital or acquired immunodeficiencies , HIV infection , chronic renal failure , nephrotic syndrome , leukemia , lymphoma , Hodgkin disease , generalized cancer , multiple myeloma , iatrogenic immunosuppression , or a history of solid organ transplantation ) . We present our findings for 4 ARTI syndromes and present a framework for antibiotic prescribing strategies for each ( Table ) . Table . Antibiotic Prescribing Strategies for Adult Patients With Acute Respiratory Tract Infection This article was review ed and approved by the Centers for Disease Control and Prevention and by the ACP High Value Care Task Force , whose members are physicians trained in internal medicine and its subspecialties and which includes experts in evidence synthesis . The Task Force developed the high-value care advice statements , which are summarized in the Figure , based on the narrative review of the literature . At each conference call , all members of the High Value Care Task Force declared all financial and nonfinancial interests . Figure . Summary of the American College of Physicians and Centers for Disease and Control and Prevention advice for high-value care on appropriate antibiotic use for acute respiratory tract infection in adults . Acute Uncomplicated Bronchitis Acute uncomplicated bronchitis is defined as a self-limited inflammation of the large airways ( bronchi ) with a cough lasting up to 6 weeks . The cough may or may not be productive ( 24 ) and is often accompanied by mild constitutional symptoms . Acute bronchitis is among the most common adult outpatient diagnoses , with about 100 million ( 10 % ) ambulatory care visits in the United States per year ( 8) , more than 70 % of which result in a prescription for antibiotics ( 25 , 26 ) . Acute bronchitis leads to more inappropriate antibiotic prescribing than any other ARTI syndrome in adults ( 8) . Determining the Likelihood of a Bacterial Infection More than 90 % of otherwise healthy patients presenting to their outpatient providers with an acute cough have a syndrome caused by a virus ( Table ) ( 10 , 21 , 22 ) . Nonviral pathogens , such as Mycoplasma pneumoniae and Chlamydophila pneumoniae , are occasionally identified in patients with acute bronchitis ( 10 ) , and Bordetella pertussis may be considered in situations where transmission in the community has been reported . However , determining whether a patient has a viral or nonviral cause can be difficult . The presence of purulent sputum or a change in its color ( for example , green or yellow ) does not signify bacterial infection ; purulence is due to the presence of inflammatory cells or sloughed mucosal epithelial cells . Acute bronchitis must be distinguished from pneumonia . For healthy immunocompetent adults younger than 70 years , pneumonia is unlikely in the absence of all of the following clinical criteria : tachycardia ( heart rate > 100 beats/min ) , tachypnea ( respiratory rate > 24 breaths/min ) , fever ( oral temperature > 38C ) , and abnormal findings on a chest examination ( rales , egophony , or tactile fremitus ) ( 10 , 27 ) . Appropriate Management Strategies The most recent clinical guidelines for management of acute uncomplicated bronchitis recommended against routine antibiotic treatment in the absence of pneumonia ( 11 ) . A systematic review of 15 r and omized , controlled trials found limited evidence to support the use of antibiotics for acute bronchitis and a trend toward increased adverse events in patients treated with antibiotics ( 28 ) . A r and omized , placebo-controlled trial ( not included in the Cochrane review ) comparing ibuprofen , amoxicillinclavulanic acid , and placebo showed no significant differences in the number of days to cough resolution ( 24 ) . Although macrolides ( azithromycin ) are frequently prescribed for patients with a cough , one study showed that patients with acute bronchitis treated with a macrolide  had significantly more adverse events than those receiving placebo ( 29 ) . Patients may benefit from symptomatic relief with cough suppressants ( dextromethorphan or codeine ) , expectorants ( guaifenesin ) , first-generation antihistamines ( diphenhydramine ) , decongestants ( phenylephrine ) , and -agonists ( albuterol ) , although data to support specific therapies are limited . -Agonists have not been shown to benefit patients without asthma or chronic obstructive lung disease ( 30 ) , and symptomatic therapy has not been shown to shorten the duration of illness ( 30 , 31 ) . Over-the-counter symptomatic relief has a low incidence of minor adverse effects , including nausea , vomiting , headache , and drowsiness ( 32 ) . Providers and patients must weigh the benefits and potential for adverse effects when considering symptomatic therapy . High-Value Care Advice 1 Clinicians should not perform testing or initiate antibiotic therapy in patients with bronchitis unless pneumonia is suspected . Pharyngitis Pharyngitis is usually a benign , self-limited illness characterized by a sore throat that is worse with swallowing , with or without associated constitutional symptoms . It is a common outpatient condition , with about 12 million visits representing 1 % to 2 % of all ambulatory care visits in the United States annually ( 33 ) . Although antibiotics are usually unnecessary , they are prescribed at most visits for pharyngitis ( 34 ) . Determining the Likelihood of a Bacterial Infection Most pharyngitis cases have a viral origin ; common causes include rhinovirus , coronavirus , adenovirus , herpes simplex virus , parainfluenza , enterovirus , EpsteinBarr virus , cytomegalovirus , and influenza ( 35 ) . Patients with a sore throat and associated symptoms  , OBJECTIVE Evidence from animal experiments and observational studies in humans suggests that vitamin A plays a fundamental role in physical growth . However , results from vitamin A supplementation trials in children are inconsistent ; whereas some did not find an overall effect on growth , others found benefits only among specific groups , including children with low concentrations of serum retinol or short duration of breastfeeding . The apparent lack of an overall effect of vitamin A on growth could be attributed to context -specific distribution of conditions that affect both growth and the response to supplementation , eg , baseline vitamin A status , deficiency of other nutrients ( fat , zinc ) , and the presence of infectious diseases . Human immunodeficiency virus ( HIV ) infection , malaria , and diarrheal disease adversely affect growth and are associated with increased prevalence of vitamin A deficiency . We hypothesize that vitamin A supplementation could ameliorate the adverse effect of these infections on child growth . METHODS We conducted a r and omized , clinical trial among 687 Tanzanian children who were 6 to 60 months of age and admitted to the hospital with pneumonia . Children were assigned to oral doses of 200 000 IU vitamin A ( half that dose if < 12 months ) or placebo on the day of admission , a second dose on the following day , and third and fourth doses at 4 and 8 months after discharge from the hospital , respectively . Anthropometric measurements were obtained at baseline and at monthly visits to the study clinics during 12 months after the initial hospitalization . Surveillance on the incidence and severity of diarrhea and respiratory infections was conducted during biweekly visits , alternately at a study clinic and the child 's home , using a pictorial diary that the mothers were trained to use . A blood specimen was drawn at baseline for determination of HIV status , malaria infection , and hemoglobin levels . We used mixed effects models to compare estimated total weight and height increases after 1 year of follow-up between treatment arms , overall and within levels of HIV status , malaria , and other possible baseline effect modifiers . We also assessed the potential modulating effect of vitamin A on the risk of stunting ( height-for-age < -2 st and ard deviations of the gender-specific National Center for Health Statistics median reference ) attributable to diarrheal and respiratory infections during follow-up , in the subset of children who were not stunted at baseline . A similar approach was followed for wasting ( weight-for-height < -2 st and ard deviations of the reference median ) . Cox regression models were used to estimate relative risks and 95 % confidence intervals ( CI ) , treating episodes of infection as time-dependent covariates . RESULTS A total of 554 children had at least 2 follow-up measurements of height or weight and constituted the study base . Baseline characteristics did not differ significantly by treatment arm . Seventy-three percent of the children were < 2 years of age , and 37 % were < 12 months ; 31 % were stunted at baseline and 9 % were wasted . Malaria ( Plasmodium falciparum ) and HIV infection were found in 24 % and 9 % of the children , respectively . Median duration of follow-up was 351 days , with 10 measurements /child , on average , irrespectively of treatment assignment . Supplementation with vitamin A among children who had HIV infection and were < 18 months of age result ed in a significant length increase . Four months after the first dose , infants who were HIV positive in the vitamin A arm had gained , on average , 2.8 cm ( 95 % CI : 1.0 - 4.6 ) more than children who received placebo , whereas no effect was observed among infants who were HIV negative ( difference at 4 months : -0.2 cm ; 95 % CI : -0.8 - 0.5 ) . Children who were < 12 months of age and had malaria at enrollment experienced a 747-g ( 95 % CI : 71 - 1423 ) higher yearly weight gain attributable to vitamin A ; among children without malaria , however , the supplements did not have a significant effect ( -57 g ; 95 % CI : -461 - 348 ) . These results remained unchanged after controlling for indicators of the socioeconomic and nutritional status at baseline . Linear growth was also improved by vitamin A among children from households with poor water supply ( 0.8 cm/year ; 95 % CI : 0 - 1.5 ) but not in children with tap water in the house or compound ( -1.0 cm/year ; 95 % CI : -1.9 - 0 ) . Weight gain was greater among children with mid-upper arm circumference below the 25th percentile of the age-specific distribution at baseline ( 458 g/year ; 95 % CI : 1 - 905 ) , but no benefit was evident among children with higher mid-upper arm circumference . The risk of stunting associated with episodes of persistent diarrhea ( lasting 14 or more days ) during follow-up was virtually eliminated by vitamin A supplements . Among children in the placebo group , the average risk of stunting associated with 1 or more episodes of persistent diarrhea between 2 consecutive visits was 5.2 times higher ( 95 % CI : 2.4 - 11.2 ) than that of children without diarrhea or with acute episodes . In contrast , among children who received vitamin A , there was virtually no risk of stunting associated with persistent diarrhea ( relative risk : 1.0 ; 95 % CI : 0.3 - 1.3 ) . This effect was slightly attenuated after controlling for the number of household possessions , gender , baseline low arm circumference , HIV infection , and presence of malaria parasites in blood . Vitamin A supplements did not modify the associations between respiratory infections and the risk of stunting or wasting . CONCLUSIONS Vitamin A supplementation improves linear and ponderal growth in infants who are infected with HIV and malaria , respectively , and decreases the risk of stunting associated with persistent diarrhea . Supplementation could constitute a low-cost , effective intervention to decrease the burden of growth retardation in setting s where infectious diseases are highly prevalent BACKGROUND Antioxidant supplementation is thought to improve immunity and thereby reduce infectious morbidity . However , few large trials in elderly people have been conducted that include end points for clinical variables . OBJECTIVE To determine the effects of long-term daily supplementation with trace elements ( zinc sulfate and selenium sulfide ) or vitamins ( beta carotene , ascorbic acid , and vitamin E ) on immunity and the incidence of infections in institutionalized elderly people . METHODS This r and omized , double-blind , placebo-controlled intervention study included 725 institutionalized elderly patients ( > 65 years ) from 25 geriatric centers in France . Patients received an oral daily supplement of nutritional doses of trace elements ( zinc and selenium sulfide ) or vitamins ( beta carotene , ascorbic acid , and vitamin E ) or a placebo within a 2 x 2 factorial design for 2 years . MAIN OUTCOME MEASURES Delayed-type hypersensitivity skin response , humoral response to influenza vaccine , and infectious morbidity and mortality . RESULTS Correction of specific nutrient deficiencies was observed after 6 months of supplementation and was maintained for the first year , during which there was no effect of any treatment on delayed-type hypersensitivity skin response . Antibody titers after influenza vaccine were higher in groups that received trace elements alone or associated with vitamins , whereas the vitamin group had significantly lower antibody titers ( P<.05 ) . The number of patients without respiratory tract infections during the study was higher in groups that received trace elements ( P = .06 ) . Supplementation with neither trace elements nor vitamins significantly reduced the incidence of urogenital infections . Survival analysis for the 2 years did not show any differences between the 4 groups . CONCLUSIONS Low-dose supplementation of zinc and selenium provides significant improvement in elderly patients by increasing the humoral response after vaccination and could have considerable public health importance by reducing morbidity from respiratory tract infections BACKGROUND Low-birth-weight ( LBW ) infants ( < 2,500 g ) are at increased risk of respiratory infection in the first few months of life and have low liver stores of vitamin A. As retinol is essential for respiratory epithelial cell differentiation , deficiency could result in pathological changes in the respiratory epithelium , with respiratory problems . OBJECTIVE A r and omised , double-blind , placebo-controlled trial to investigate the effect of vitamin A supplementation on the incidence and severity of respiratory infections in LBW infants during their first year of life . METHOD One hundred and thirty LBW infants ( gestational age < 36 weeks and birth weight 950 - 1,700 g ) were enrolled in the study . The infants were r and omly allocated to a vitamin A or placebo group . Infants in the vitamin A group received 25,000 IU of vitamin A ( retinyl palmitate , Arovit drops , Roche , Basle , Switzerl and ) on study days 1 , 4 and 8 . Study day 1 was between 36 and 60 hours after delivery . Infants in the placebo group received a placebo ( formulated by Roche ) with a similar appearance and packed in the same dropper bottles as the vitamin A drops . RESULTS Vitamin A supplementation markedly improved serum retinol levels . After the last vitamin A dose , the vitamin A group had higher mean serum retinol concentrations than the placebo group ( 45.77 + /- 17.07 micrograms/dl v. 12.88 + /- 6.48 micrograms/dl , P = 0.0001 ) . There was no evidence of improvement in neonatal or post-neonatal respiratory problems associated with vitamin A supplementation . Vitamin A and placebo groups did not differ in the occurrence or duration of respiratory distress or the need for head-box oxygen . There were also no significant differences in the cumulative probability of developing lower or upper respiratory tract infection through the first year of life . There was a slight suggestion of an increase in the risk of hospitalisation with pneumonia associated with vitamin A supplementation . The cumulative probability of being hospitalised with pneumonia by 6 months of age was 24.6 % ( 7 hospitalisations ) in the vitamin A group compared with 7.4 % ( 2 hospitalisations ) in the placebo group ( log rank test P = 0.04 ) . After adjusting for risk factors this difference was no longer significant . CONCLUSION Vitamin A supplementation in LBW neonates may not reduce incidence or severity of respiratory infections . These results do not negate the importance of improving vitamin A status in children as an important public health measure to reduce morbidity and mortality from other childhood infections Nasopharyngeal colonization is a risk factor for pneumococcal disease , a leading cause of complications and death in infants . We assessed the impact of vitamin A supplementation in reducing pneumococcal colonization in infants from an area with endemic vitamin A deficiency . We recruited 464 2-mo-old infants from a rural area in South India . Infants were r and omly assigned to receive two 7000-microg retinol equivalent doses of vitamin A ( n = 239 ) or placebo ( n = 225 ) orally at birth , and nasopharyngeal specimens were collected at ages 2 , 4 and 6 mo . We studied the effect of vitamin A on culture-confirmed pneumococcal colonization and on the distribution of pneumococcal serotypes . Analyses were conducted by intention-to-treat . The risk of colonization among infants aged 4 mo who were not colonized by age 2 mo was significantly reduced in the vitamin A group compared with the placebo group [ odds ratio 0.51 ( 0.28 , 0.92 ) , P = 0.02 ) . The odds of colonization were 27 % lower in the treatment group than in the placebo group [ odds ratio 0.73 ( 0.48 , 1.1 ) , P = 0.13 ] . No differences were detected in the prevalence of invasive serotypes . The risk of colonization with penicillin-resistant isolates was 74 % lower in the vitamin A group than in the placebo group at 2 mo of age . However , the prevalence of penicillin-resistant isolates was only 4 % . Neonatal vitamin A supplementation may play a role in lowering morbidity rates associated with pneumococcal disease by delaying the age at which colonization occurs Background The Need To Improve Antibiotic Prescription for Acute Respiratory Infections 1 . The epidemic increase in antibiotic-resistant Streptococcus pneumoniae is an ambulatory care problem . Excessive use of antibiotics in ambulatory practice has contributed to the emergence and spread of antibiotic-resistant bacteria in the community ( 1 - 4 ) . Penicillin resistance in S. pneumoniae has increased in an epidemic manner in the past 10 years ( 5 , 6 ) . Resistance to macrolides , doxycycline , trimethoprimsulfamethoxazole , and second- and third-generation cephalosporins has also increased . Special attention to antibiotic-resistance profiles of S. pneumoniae is warranted , since this pathogen is the leading cause of community-acquired bacterial pneumonia , bacterial meningitis , bacterial sinusitis , and otitis media in the United States ( 7 ) . 2 . Previous antibiotic use is an important risk factor for carriage of and infection with antibiotic-resistant Streptococcus pneumoniae . The major risk factors for carriage of and infection with antibiotic-resistant S. pneumoniae are geographic location , recent exposure to antibiotics , and exposure to young children . Carriage of S. pneumoniae ( and antibiotic-resistant S. pneumoniae ) primarily occurs in the nasopharynx and oropharynx of susceptible hosts ( 8 , 9 ) . Factors contributing to the spread of S. pneumoniae ( such as close contact and viral respiratory infections ) are also associated with the spread of antibiotic-resistant S. pneumoniae ( 10 - 12 ) . For example , carriage and transmission of antibiotic-resistant S. pneumoniae are greatest during winter months and in environments that facilitate the transmission of respiratory secretions ( 8) . The prevalence of carriage of S. pneumoniae and antibiotic-resistant S. pneumoniae appears to be greatest in young children ; up to one third of children who visit health clinics are reported to be nasopharyngeal carriers of antibiotic-resistant S. pneumoniae ( 13 - 15 ) . The prevalence of S. pneumoniae colonization in the upper airways in adults is about 5 % ; this value increases if children are present in the household ( 10 ) . Although the risks for transmission of antibiotic-resistant S. pneumoniae mirror those for S. pneumoniae , numerous retrospective and prospect i ve carriage studies have also identified previous antibiotic use , especially for a prolonged period ( for example , as prophylaxis against recurrent acute otitis media ) , to be the most significant risk factor for carriage and subsequent spread of antibiotic-resistant S. pneumoniae ( 14 - 18 ) . The risk for carriage of antibiotic-resistant S. pneumoniae is two to nine times greater in persons who have recently used antibiotics . A precipitously rapid increase in antibiotic resistance has also been observed for strains of S. pneumoniae in blood , cerebrospinal fluid , and joint fluid in the United States since 1986 , when invasive antibiotic-resistant S. pneumoniae isolates were rare or absent ( 5 ) . Like carriage of antibiotic-resistant S. pneumoniae , invasive infection with antibiotic-resistant S. pneumoniae is associated with previous antibiotic use ( 6 , 19 - 22 ) . When invasive infection with antibiotic-resistant S. pneumoniae occurs , antibiotics with poor central nervous system penetration and bacteriostatic ( instead of bactericidal ) properties must sometimes be used . Treatment failures have been reported in patients with pneumococcal meningitis after therapy with penicillin , chloramphenicol , clarithromycin , ceftriaxone , and cefotaxime ( 12 , 23 - 26 ) . The management of outpatient bacterial infections , such as acute otitis media , becomes substantially more difficult because of high rates of antibiotic-resistant S. pneumoniae in children with such infections ( 27 , 28 ) . However , few studies have quantified the clinical impact of antibiotic-resistant S. pneumoniae on morbidity , mortality , and health care costs in children or adults . In a study of hospitalized patients with severe pneumococcal pneumonia in Spain , where a high prevalence of antibiotic-resistant S. pneumoniae preceded the current increase in the United States , no association was seen between antibiotic resistance and mortality ( 29 ) . However , most patients had intermediate-level penicillin resistance ; in such patients , serum and lung interstitium concentrations of antibiotic are sufficiently high to overcome resistance . A recent study of U.S. adults hospitalized with community-acquired pneumonia due to S. pneumoniae found that mortality was significantly associated with high-level antibiotic-resistant S. pneumoniae ( minimum inhibitory concentration 4 g/mL ) , after exclusion of deaths that occurred within the first 2 to 4 days of hospitalization ( 30 ) . Exclusion of early deaths is justified , since antibiotic therapy has not been shown to affect early mortality in adults with antibiotic-susceptible pneumococcal disease ( 31 ) . Because of the current increase in antibiotic resistance in community bacterial pathogens , many experts are predicting an impending postantibiotic era ( 2 - 4 ) . 3 . Most antibiotic prescriptions in the ambulatory setting are for acute respiratory infections . Intervention strategies aim ed at reducing community use of antibiotics must address the management of acute respiratory infections . These illnesses are the most frequent reasons for seeking medical attention in the United States , and they are associated with up to 75 % of total antibiotic prescriptions each year ( 32 ) . Transmission of S. pneumoniae is enhanced during viral acute respiratory infection through increased respiratory and nasal secretions ( 10 ) . As a result , antibiotic treatment of viral acute respiratory infections is particularly problematic , since it may selectively promote the acquisition and spread of antibiotic-resistant bacteria by patients . Specific acute respiratory infections that must be targeted for reducing unnecessary antibiotic use in adults are uncomplicated acute bronchitis ( not including acute exacerbations of chronic bronchitis ) , acute sinusitis , pharyngitis , and nonspecific upper respiratory tract infection ( including the common cold ) . These diagnoses are usually made in the presence of a clinical syndrome with a predominant clinical feature , so that prominent acute cough is taken to mean acute bronchitis , prominent nasal and sinus symptoms are thought to signify sinusitis , and prominent acute sore throat is considered pharyngitis . Acute respiratory symptoms in the absence of a predominant symptom are typically diagnosed as upper respiratory tract infection . Each of these syndromes can be caused by a multitude of different viruses and , on occasion , bacteria . The degree of excess prescription of antibiotics varies for each diagnosis . Antibiotic treatment of a cold , an upper respiratory tract infection , or acute bronchitis is almost always inappropriate because the vast majority of these syndromes have a nonbacterial cause . Antibiotic treatment of sinusitis and pharyngitis is sometimes justified but should be limited to appropriate subsets of patients . Potential Benefit and Harm of Adherence to Principles of Appropriate Antibiotic Prescription Potential Benefits of Indiscriminant Antibiotic Prescription Some clinicians may prescribe antibiotics because they believe that a very small fraction of patients might benefit or they hope to prevent the remote case of a bad outcome ( and a potential lawsuit ) . A theoretical clinical benefit of treating viral respiratory tract infections with antibiotics can not be excluded . A truism for all clinical trials performed in medicine is that a benefit of treatment can not be excluded for outcomes that occur less frequently than the sample size can detect ( that is , there will always be specific outcomes that were not or can not be measured ) . For example , invasive bacterial disease , such as sepsis or bacterial meningitis , is too rare an event to be evaluated in a r and omized , controlled trial with enough power to exclude a potential benefit of antibiotic treatment . The incidence of bacterial meningitis in the United States is about 3 per 100 000 persons in the general population ( 1995 ) ( 33 ) or about 9 per 100 000 persons with an office visit for an acute respiratory illness ( unpublished data based on the National Ambulatory Medical Care Survey , 1997 ) . Indiscriminant use of antibiotics may also in theory prevent complications of other undiagnosed bacterial infections , such as acute rheumatic fever . While these hypothetical benefits are possible , no evidence supports their existence . Potential Harms of Indiscriminant Antibiotic Prescription In contrast to the theoretical clinical benefit of indiscriminant prescription of antibiotics , the potential harm of this practice is well established at the level of the patient and society . At the patient level , risks include allergic reactions ( such as urticaria , rash , and anaphylaxis ) , adverse reactions ( such as gastrointestinal discomfort or yeast infections ) , and drugdrug interactions ( such as QT interval prolongation caused by warfarin and oral contraceptives ) , as well as the increased likelihood that a pneumococcal infection in the ensuing months will be due to an antibiotic-resistant strain . At the societal level , the adverse effects of indiscriminant antibiotic use on rates of antibiotic resistance are well established , and the effects on health care costs ( for antibiotics and office visits ) are straightforward . Finally , indiscriminant antibiotic use could serve to inappropriately medicalize viral illnesses . This tendency not only usurps the ability of individual persons to care for self-limited illnesses but also carries large associated costs in terms of unnecessary office visits and prescriptions . Potential Benefits of Limiting Indiscriminant Antibiotic Prescription Besides decreasing the risk for the harms noted above , the intended result of efforts to decrease indiscriminant antibiotic use in the ambulatory setting is to reduce ( and preferably reverse ) the increase in Vitamin A supplementation of population s of vitamin A-deficient preschool-age children has been shown to reduce childhood mortality , but the primary preventive effects of such supplements on childhood infectious diseases have not been carefully evaluated . We conducted an individually r and omized , placebo-controlled , double-masked trial among 1,407 Indonesian preschool-age children , to measure the effects of high dose vitamin A on acute respiratory and diarrheal illnesses . Signs and symptoms of morbidity were monitored using every other day home surveillance by trained interviewers . High dose vitamin A supplements increased the incidence of acute respiratory illnesses ( ARI ) by 8 % , and acute lower respiratory illnesses ( ALRI ) by 39 % . These detrimental effects on acute lower respiratory illnesses were most marked in children with adequate nutritional status ( rate ratio 1.83 , 95 % confidence interval 1.257 - 2.669 ) . In contrast , vitamin A tended to be protective of ALRI in chronically malnourished children ( rate ratio 0.71 , 95 % confidence interval 0.375 - 1.331 ) . There was no overall effect of high-dose vitamin A supplements on the incidence of diarrheal disease ( rate ratio 1.06 , 95 % confidence interval 0.920 - 1.225 ) . However , we found a significant interaction between supplementation and age : vitamin A increased the incidence of diarrhea in children < 30 mo of age , but tended to reduce the incidence in older children . The finding of a significant adverse effect of vitamin A supplements in adequately nourished children highlights the need to review the criteria for selecting population s of preschool-age children for vitamin A supplementation Abstract Objective : To evaluate the impact on clinical recovery and severity of the addition of large doses of vitamin A to the st and ard treatment for childhood pneumonia . Design : A r and omised , double blind , placebo controlled trial . Setting : Study children were recruited at a public hospital in Recife , north east Brazil , an area of marginal vitamin A deficiency . Subjects : 472 children aged 6 to 59 months with clinical diagnosis of pneumonia . Interventions : 200 000 IU ( infants ) or 400 000 IU ( 1 - 4 year olds ) of vitamin A in oil or similar capsules of placebo divided into two daily oral doses , in addition to the st and ard treatment . Main outcome measures : Duration of the episode and incidence of adverse outcomes . Results : The groups were similar with respect to overall duration of pneumonia and incidence of adverse outcomes . Children who received vitamin A , however , were less likely to have fever by day 3 ( P=0.008 ) and were 29 % less likely to fail to respond to the first line antibiotic ( P=0.054 ) . Conclusion : There was little evidence for an effect of vitamin A treatment on the immediate outcome of the pneumonia episode . Key messages Pneumonia is a leading cause of childhood mortality in developing countries Vitamin A supplementation has no impact on mortality from pneumonia even though it reduces overall mortality Treatment of measles pneumonia with vitamin A reduces case fatality and severity of disease This study showed that vitamin A treatment has no impact on the recovery from non-measles pneumonia , despite some suggestion that severely affected patients may benefit The addition of vitamin A for treatment protocol s for childhood pneumonia is not recommended for clinical cure , although it maybe a useful contact to improve vitamin A BACKGROUND Multiple micronutrients ( vitamin B complex and vitamins C and E ) were effective at reducing infectious disease morbidity , HIV disease progression , and poor pregnancy outcomes in HIV-infected women . OBJECTIVE The objective was to evaluate whether direct supplementation of these micronutrients to HIV-exposed infants reduces mortality and morbidity . DESIGN Infants born to HIV-infected women from Dar es Salaam , Tanzania , were r and omly assigned to receive daily oral supplementation of multiple multivitamins ( vitamin B complex and vitamins C and E ) or placebo from age 6 wk for 24 mo . All-cause mortality , hospitalizations , and unscheduled clinic visits were recorded . Morbidities were recorded during monthly follow-up visits . All mothers received multiple micronutrients throughout the study . RESULTS A total of 1193 infants were r and omly assigned to receive  micronutrients  and 1194 to receive placebo .  There were 138 child deaths in the multivitamin group and 124 deaths in the placebo group ( HR : 1.13 ; 95 % CI : 0.88 , 1.44 ; P = 0.33 ) . Hospitalizations ( RR : 0.83 ; 95 % CI : 0.62 , 1.13 ; P = 0.23 ) , unscheduled clinic visits ( RR : 0.97 ; 95 % CI : 0.85 , 1.10 ; P = 0.59 ) , and maternal reports of diarrhea ( RR : 0.97 ; 0.87 , 1.10 ; P = 0.64 ) were not significantly different between the 2 groups . Fever ( P = 0.02 ) and vomiting ( P = 0.007 ) were significantly lower in the multivitamin group . Among 429 children whose mothers received antiretroviral ( ARV ) therapy , multivitamin use had no effect on mortality but was associated with a significant reduction in hospitalizations ( P = 0.035 ) , episodes of fever ( P = 0.005 ) , and episodes of fever and cough ( P = 0.019 ) . CONCLUSIONS In the setting of maternal micronutrient supplementation , supplementation of HIV-exposed infants with vitamin B and vitamins C and E does not reduce mortality . Studies of nutrition supplementation in ARV-exposed infants may be warranted
Due to the small number of included studies and very low quality of the existing evidence , we are uncertain of the effect of vitamin C supplementation for the prevention and treatment of pneumonia .
BACKGROUND According to the Global Burden of Disease Study 2015 , lower respiratory tract infection is the leading cause of infectious disease death , and the fifth most common cause of death overall .
Vitamin C has a role in modulating resistance to infectious agents , therefore vitamin C supplementation may be important in preventing and treating pneumonia .
OBJECTIVES To assess the impact of vitamin C supplementation to prevent and treat pneumonia in children and adults .