Antibiotic Treatment Regimens Research Articles

Klebsiella pneumoniae Invasive Syndrome.

Klebsiella pneumoniae invasive syndrome (KPIS) is a rare clinical condition characterized by primary liver abscess associated with metastatic infection. Most case reports are from Southeast Asia, with only one case described in Portugal. The Authors present the case of a 44-year-old man with a history of fever, dry cough and cervicalgia. A thoracic computed tomography (CT) scan showed multiple pulmonary and hepatic nodules, suggestive of metastatic malignancy. Both blood cultures and bronchoalveolar lavage were positive for Klebsiella pneumoniae. Imaging studies were repeated during his hospital stay, showing a reduction in both number and volume of identified lesions, thus revealing their infectious nature. This case illustrates how much this entity can mimic other illnesses.LEARNING POINTSKlebsiella pneumoniae invasive syndrome is emerging as a global disease.The imaging-led diagnosis of neoplasia was proved incorrect and could have been deleterious for the patient.The lack of diagnostic suspicion can lead to shorter antibiotic treatment regimens, therefore compromising the patient’s full recovery.

Influence of probiotics assisted with routine antibiotic regimens on the short-term clinical efficacy, mucosal barrier function and inflammatory response of patients with bacterial peritonitis secondary to liver cirrhosis

Objective To investigate the influence of probiotics assisted with routine antibiotic regimens on the short-term clinical efficacy, mucosal barrier function and inflammatory response of patients with bacterial peritonitis secondary to liver cirrhosis. Methods 60 patients with bacterial peritonitis secondary to liver cirrhosis were chosen, and they were randomly divided into two groups according to the digital table, each group in 30 cases.The control group received routine antibiotic regimens alone, and the observation group were given probiotics on the basis of the control group.The short-term clinical efficacy, the levels of DAO, D-Lac and ET before and after treatment of the two groups were compared. Results The short-term effective rates of the control group and observation group were 70.00%, 96.67%, respectively.The short-term effective rate of the observation group was significantly higher than that of control group(χ2=9.14, P<0.05). After treatment, the levels of DAO of the control group and observation group were (4.33±0.79)U/mL, (2.19±0.47)U/mL, respectively.The levels of D-Lac of the control group and observation group after treatment were (15.88±1.95)U/mL, (8.57±1.03)U/mL, respectively.The levels of DAO and D-Lac of the observation group after treatment were significantly lower than those of the control group and before treatment(t=2.78, 3.06; 3.44, 3.78, 3.61, 4.10, all P<0.05). The levels of ET of the control group and observation group after treatment were (0.09±0.02)EU/mL, (0.04±0.01)EU/mL, respectively.The level of ET of the observation group after treatment was significantly lower than that of the control group and before treatment(t=2.49, 3.01, 3.46, all P<0.05). Conclusion Probiotics assisted with routine antibiotic regimens in the treatment of patients with bacterial peritonitis secondary to liver cirrhosis can effectively relieve the symptoms and signs, improve the mucosal barrier function and is helpful to reduce the inflammatory response. Key words: Probiotics; Peritonitis; Cirrhosis; Anti-infective ageuts

Antibiotic resistance of Helicobacter pylori in Mongolia.

The resistance of Helicobacter pylori to recently available antibiotic treatment regimens has been recognized as a growing problem. Therefore, the aim of this study was to determine the prevalence of antibiotic resistance among H. pylori strains isolated from Mongolians. All gastric biopsy specimens were obtained during upper gastrointestinal endoscopy from patients referred for the exploration of dyspepsia. The urease positive samples by rapid urease test were cultured according to standard microbiological procedures and H. pylori were grown under microaerophilic conditions on selective Pylori agar. H. pylori antibiotic sensitivity was examined using E-test. In addition, the mutations of the corresponding gene were studied by GenoType HelicoDR DNA strip testing. Three hundred twenty patients, 216 female and 104 male in the ages range of 18 to 83 years were included in this study. Rapid urease test yielded positive results for 65.9% (211/320). Among them, we have successfully obtained 72% H. pylori isolates. The antibiotic resistance rates were 35.5% for clarithromycin, 68.4% metronidazole, 23.0% amoxicillin, 25.0% tetracycline, 28.2% erythromycin and 14.5% nitrofuranton. Resistance for 2 drugs was 34.5% and that of 3 drugs was observed in 14.5% of isolates. The most prevalent mutation was A2147G followed by A2146G and D91Y. The prevalence of H. pylori infection increased among Mongolian population and the prevalence of resistance of H. pylori is very high to metronidazole, and moderate to clarithromycin. The data on antimicrobial susceptibilities provided by the present study is may assist the clinicians on the effectiveness of treatment regimens.

What is the best empiric antibiotic treatment regimen in adults hospitalized with community-acquired pneumonia?

What is the best empiric antibiotic treatment regimen in adults hospitalized with community-acquired pneumonia?

Geographically widespread honeybee‐gut symbiont subgroups show locally distinct antibiotic‐resistant patterns

How long-term antibiotic treatment affects host bacterial associations is still largely unknown. The honeybee-gut microbiota has a simple composition, so we used this gut community to investigate how long-term antibiotic treatment affects host-associated microbiota. We investigated the phylogenetic relatedness, genomic content (GC percentage, genome size, number of genes and CRISPR) and antibiotic-resistant genes (ARG) for strains from two abundant members of the honeybee core gut microbiota (Gilliamella apicola and Snodgrassella alvi). Domesticated honeybees are subjected to geographically different management policies, so we used two research apiaries, representing different antibiotic treatment regimens in their apiculture: low antibiotic usage (Norway) and high antibiotic usage (Arizona, USA). We applied whole-genome shotgun sequencing on 48G.apicola and 22 S.alvi. We identified three predominating subgroups of G.apicola in honeybees from both Norway and Arizona. For G.apicola, genetic content substantially varied between subgroups and distance similarity calculations showed similarity discrepancy between subgroups. Functional differences between subgroups, such as pectin-degrading enzymes (G.apicola), were also identified. In addition, we identified horizontal gene transfer (HGT) of transposon (Tn10)-associated tetracycline resistance (Tet B) across the G.apicola subgroups in the Arizonan honeybees, using interspace polymorphisms in the Tet B determinant. Our results support that honeybee-gut symbiont subgroups can resist long-term antibiotic treatment and maintain functionality through acquisition of geographically distinct antibiotic-resistant genes by HGT.

Predicting the dynamics of bacterial growth inhibition by ribosome-targeting antibiotics

Understanding how antibiotics inhibit bacteria can help to reduce antibiotic use and hence avoid antimicrobial resistance—yet few theoretical models exist for bacterial growth inhibition by a clinically relevant antibiotic treatment regimen. In particular, in the clinic, antibiotic treatment is time-dependent. Here, we use a theoretical model, previously applied to steady-state bacterial growth, to predict the dynamical response of a bacterial cell to a time-dependent dose of ribosome-targeting antibiotic. Our results depend strongly on whether the antibiotic shows reversible transport and/or low-affinity ribosome binding (‘low-affinity antibiotic’) or, in contrast, irreversible transport and/or high affinity ribosome binding (‘high-affinity antibiotic’). For low-affinity antibiotics, our model predicts that growth inhibition depends on the duration of the antibiotic pulse, and can show a transient period of very fast growth following removal of the antibiotic. For high-affinity antibiotics, growth inhibition depends on peak dosage rather than dose duration, and the model predicts a pronounced post-antibiotic effect, due to hysteresis, in which growth can be suppressed for long times after the antibiotic dose has ended. These predictions are experimentally testable and may be of clinical significance.

Carbapenemase-Producing Organisms: A Global Scourge.

The dramatic increase in the prevalence and clinical impact of infections caused by bacteria producing carbapenemases is a global health concern. Carbapenemase production is especially problematic when encountered in members of the family Enterobacteriaceae. Due to their ability to readily spread and colonize patients in healthcare environments, preventing the transmission of these organisms is a major public health initiative and coordinated international effort are needed. Central to the treatment and control of carbapenemase-producing organisms (CPOs) are phenotypic (growth-/biochemical-dependent) and nucleic acid-based carbapenemase detection tests that identify carbapenemase activity directly or their associated molecular determinants. Importantly, bacterial isolates harboring carbapenemases are often resistant to multiple antibiotic classes, resulting in limited therapy options. Emerging agents, novel antibiotic combinations and treatment regimens offer promise for management of these infections. This review highlights our current understanding of CPOs with emphasis on their epidemiology, detection, treatment, and control.

Antibiotic exposure and interpersonal variance mask the effect of ivacaftor on respiratory microbiota composition

BackgroundG551D is a class III mutation of the cystic fibrosis transmembrane regulator (CFTR) that results in impaired chloride channel function in cystic fibrosis (CF). Ivacaftor, a CFTR-potentiating agent improves sweat chloride, weight, lung function, and pulmonary exacerbation rate in CF patients with G551D mutations, but its effect on the airway microbiome remains poorly characterised. MethodsTwenty CF patients with at least one G551D mutation from a single centre were recruited to a 4month double-blind, placebo-controlled, crossover study of ivacaftor with 28days of active treatment. Sputum microbiota composition was assessed by 16S rRNA gene amplicon sequencing and quantitative PCR at five key time points, along with regular clinical review, respiratory function assessment, and peripheral blood testing. ResultsNo significant difference in microbiota composition was observed in subjects following ivacaftor treatment or placebo (PERMANOVA P=0.95, square root ECV=−4.94, 9479 permutations). Microbiota composition variance was significantly greater between subjects, than within subjects over time (P<0.0001, Mann Whitney U test), and an additional within-patient paired assessment of microbiota similarity was therefore performed. Again, change in microbiota composition was not significantly greater during treatment with ivacaftor compared to placebo (Wilcoxon test, P=0.51). A significant change in microbiota composition was however associated with any change in antibiotic exposure, regardless of whether ivacaftor or placebo was administered (P=0.006). In a small, subgroup analysis of subjects whose antibiotic exposure did not change within the study period, a significant reduction in total bacterial load was observed during treatment with ivacaftor (P=0.004, two-tailed paired Student's t-test). ConclusionsThe short-term impact of ivacaftor therapy on sputum microbiota composition in patients with G551D mutations are modest compared to those resulting from antibiotic exposure, and may be masked by changes in antibiotic treatment regimen.

Applying optimization algorithms to tuberculosis antibiotic treatment regimens.

Tuberculosis (TB), one of the most common infectious diseases, requires treatment with multiple antibiotics taken over at least 6 months. This long treatment often results in poor patient-adherence, which can lead to the emergence of multi-drug resistant TB. New antibiotic treatment strategies are sorely needed. New antibiotics are being developed or repurposed to treat TB, but as there are numerous potential antibiotics, dosing sizes and potential schedules, the regimen design space for new treatments is too large to search exhaustively. Here we propose a method that combines an agent-based multi-scale model capturing TB granuloma formation with algorithms for mathematical optimization to identify optimal TB treatment regimens. We define two different single-antibiotic treatments to compare the efficiency and accuracy in predicting optimal treatment regimens of two optimization algorithms: genetic algorithms (GA) and surrogate-assisted optimization through radial basis function (RBF) networks. We also illustrate the use of RBF networks to optimize double-antibiotic treatments. We found that while GAs can locate optimal treatment regimens more accurately, RBF networks provide a more practical strategy to TB treatment optimization with fewer simulations, and successfully estimated optimal double-antibiotic treatment regimens. Our results indicate surrogate-assisted optimization can locate optimal TB treatment regimens from a larger set of antibiotics, doses and schedules, and could be applied to solve optimization problems in other areas of research using systems biology approaches. Our findings have important implications for the treatment of diseases like TB that have lengthy protocols or for any disease that requires multiple drugs.

Treatment strategies for chronic osteomyelitis in low- and middle-income countries: systematic review.

To identify a standard treatment regime or highly successful procedure for chronic osteomyelitis in low- and middle-income countries. Systematic review following PRISMA guidelines. The initial search resulted in 102 studies of which nine met the inclusion criteria and were analysed qualitatively. The included studies involved 1173 patients from Africa and Asia. All patients were diagnosed with chronic osteomyelitis. Surgical and antibiotic treatment regimens differed substantially. No better judgement than moderate risk of selection bias could be made due to the study designs. The evidence is not sufficiently robust to identify the most effective treatment, or to even allow a recommendation of the best suitable treatment of chronic osteomyelitis in low-income countries.

Wolf’s Panniculitis

A 28-year-old male patient, presented with a one-week history of pain and itching on the skin of the left upper leg. Erythematous indurated, warm and painful on palpation, subcutaneous plaques and nodules were clinically observed, affecting the skin of the left upper leg, within a recent black-wolf tattoo. The diagnosis of traumatic panniculitis with superposed bacterial infection, provoked by a wolf tattoo was made. The patient underwent 7-days systemic antibiotic treatment regimen and topical application of iodine povidone unguent under occlusion for 7 days. Significant alleviation of the subjective complaints was achieved within the first week, with a total clinical resolution of the symptoms. The role of the procedure as a source of trauma for subcutaneous inflammation (traumatic panniculitis) and the contamination of the equipment or the staff (infective panniculitis) in simultaneously triggering of the pathogenetic chain of the reported Wolf’s panniculitis could be present.

P140 A need to reinforce the importance of pregnancy testing and correct antibiotic regimen: a re-audit of pid management against bashh guidelines

IntroductionBASHH guidelines (2011) for the management of pelvic inflammatory disease (PID) recommend one of two antibiotic regimens for outpatient treatment. In addition, patients should be offered a pregnancy test and full screening for sexually transmitted infections (STI).Aim(s)/objectivesTo review PID management across the sexual health clinics, comparing it to the previous year’s audit and BASHH guidelines.MethodsData was retrospectively collected from December 2015 until March 2016. Data collected included whether pregnancy was excluded, STI screening, antibiotic regimen used, provision of written information, partner notification, and outcome at any follow up.Results51 patients were identified, 2 were excluded due to treatment by their GP. 100% of cases had at least one sign or symptom suggestive of PID. 47/49 (96%) of cases had STI screening; 41/49 (84%) had a HIV screen as part of this. Pregnancy was excluded in 22/49 (45%) of cases. A BASHH recommended antibiotic regimen was used in 28/49 (57%) of cases. Of the 21 of non-compliant cases, only 4/21 had a documented allergy or intolerance that precluded standard treatment.DiscussionSince the last audit, recommended antibiotic treatment for PID has improved, but remains low at 57%. Pregnancy exclusion was low at 45%, compared with 70% at the last audit. Differences in how healthcare professionals record information on the electronic system could partially account for this. Actions have been taken to improve treatment and pregnancy testing by giving individual feedback to the clinicians, with a re-audit planned to assess the outcome of these interventions.

Outcomes associated with antibiotic regimens for treatment of Mycobacterium abscessus in cystic fibrosis patients

BackgroundMycobacterium abscessus infection is associated with declining lung function in cystic fibrosis (CF), but there is little evidence on clinical efficacy to guide treatment. MethodsRetrospective review of 37 CF patients treated for M. abscessus respiratory infection at a single center from 2006 to 2014. Outcomes included change in FEV1 at 30, 60, 90, 180, and 365days after treatment and clearance of M. abscessus from sputum cultures. ResultsLung function was significantly improved after 30 and 60days of treatment, but not at later time points. Gains were inversely related to starting lung function. Antibiotic choices did not influence outcomes except for greater clearance with clarithromycin. ConclusionsTreatment of M. abscessus resulted in short term improvement in lung function that is inversely related to pre-treatment FEV1.

Retrospective survey and evaluation of first-line antibiotics for chemotherapy-induced febrile neutropenia in patients with acute myeloid leukemia.

ABSTRACTPatients with acute leukemia are susceptible to chemotherapy-induced severe myelosuppression, and therefore are at a high risk for febrile neutropenia (FN). In such cases, the use of broad-spectrum antibiotics such as fourth-generation cephalosporins and carbapenems is recommended as first-line antimicrobial treatment; however, the effectiveness of these agents in patients with acute myeloid leukemia (AML) has not been investigated in detail. We retrospectively examined and evaluated the effectiveness of first-line antibiotic treatment regimens for chemotherapy-induced FN in patients with AML in Japanese Red Cross Nagoya Daiichi Hospital. The evaluated first-line treatment regimens were as follows: cefozopran (CZOP) + amikacin (AMK) in 38 cases, cefepime (CFPM) alone in 2 cases, CFPM + AMK in 2 cases, piperacillin (PIPC) + AMK in 2 cases, and CZOP alone in 1 case. Additionally, prophylactic antifungal agents were administered in all cases. Markedly effective, effective, moderately effective, and ineffective responses occurred in 31.1%, 8.9%, 8.9%, and 51.1%, respectively, of the treated cases. The response rate, defined as the combination of markedly effective and effective outcomes, was 40.0%. In 11 cases, impairment of renal functions were observed, and they were associated with combination treatments including AMK; nine of these were associated with a glycopeptide. The combination of CZOP with AMK (84.4%) was the most commonly used first-line treatment for FN in patients with AML; carbapenem or tazobactam/PIPC has never been used for treatment of such cases. Our findings demonstrate that fourth-generation cephems will be an effective first-line treatment for FN in patients with AML in our hospital.

Current practice of antibiotic prophylaxis for surgical fixation of closed long bone fractures: a survey of 297 members of the Orthopaedic Trauma Association

BackgroundThe risk of postoperative surgical site infection after long bone fracture fixation can be decreased with appropriate antibiotic use. However, there is no agreement on the superiority of a single- or multiple-dose perioperative regimen of antibiotic prophylaxis. The purpose of this study is to determine the following: 1) What are the current practice patterns of orthopaedic trauma surgeons in using perioperative antibiotics for closed long bone fractures? 2) What is the current knowledge of published antibiotic prophylaxis guidelines among orthopaedic trauma surgeons? 3) Are orthopaedic surgeons willing to change their current practices?MethodsA questionnaire was distributed via email between September and December 2015 to 955 Orthopaedic Trauma Association members, of whom 297 (31%) responded.ResultsMost surgeons (96%) use cefazolin as first-line infection prophylaxis. Fifty-nine percent used a multiple-dose antibiotic regimen, 39% used a single-dose regimen, and 2% varied this decision according to patient factors. Thirty-six percent said they were unfamiliar with Centers for Disease Control and Prevention (CDC) antibiotic prophylaxis guidelines; only 30% were able to select the correct CDC recommendation from a multiple-choice list. However, 44% of surgeons said they followed CDC recommendations. Fifty-six percent answered that a single-dose antibiotic prophylaxis regimen was not inferior to a multiple-dose regimen. If a level-I study comparing a single preoperative dose versus multiple perioperative antibiotic dosing regimen for treatment of closed long bone fractures were published, most respondents (64%) said they would fully follow these guidelines, and 22% said they would partially change their practice to follow these guidelines.ConclusionThere is heterogeneity in the use of single- versus multiple-dose antibiotic prophylaxis for surgical repair of closed long bone fractures. Many surgeons were unsure of current evidence-based recommendations regarding perioperative antibiotic use. Most respondents indicated they would be receptive to high-level evidence regarding the single- versus multiple-dose perioperative prophylactic antibiotics for the treatment of closed long bone fractures.

Lebanese Registry in the Management of Antibiotic Associated Diarrhea in Children: Observational Study in Daily Practice

Background: Antibiotic-associated diarrhea (AAD) is a common complication in patients prescribed antibiotics, and represents an economic and health burden. Evidence that probiotics may be beneficial for the prevention of AAD is increasing. The aims of this registry were to assess the prevalence of probiotic prescriptions in pediatric patients for whom an antibiotic treatment regimen was prescribed, and to explore the potential health benefits that such an administration may provide. Methods: This longitudinal, multicenter, observational study enrolled 249 pediatric patients prescribed an antibiotic treatment for 5 - 14 days, with or without a concomitant probiotic. The number of probiotic-administered patients, and AAD incidence rates throughout the 15-day follow-up period, were assessed. Results: Of the 246 patients who met inclusion/exclusion criteria in Lebanon, the investigators had prescribed an additional probiotic treatment to 118 (48%) of them, while, the other 128 (52%) did not receive such additional treatment. A significantly higher number of patients in the probiotic group were at high risk of developing diarrhea (probiotic: 27.1% vs. no probiotic: 6.3%; P < 0.001). Among high risk patients, the frequency of diarrhea was doubled in the group with no probiotics (probiotic: 21.9% (n = 7) vs. no probiotic: 50.0% (n = 4); P = 0.182). Despite the significantly larger number of probiotic-administered patients that were at high risk of developing diarrhea, the proportion of patients who reported developing diarrhea was not statistically different between the two groups (probiotic: n = 22 (18.6%) vs. no probiotic: n = 24 (18.8%); P = 0.983). Conclusions: In conclusion, this Lebanese disease registry demonstrated that almost half of pediatric patients with mild to moderate infections were prescribed probiotics in combination with antibiotics to decrease the risk of AAD. This observation was particularly significant in the high risk population as per the treating physicia n’ s judgment. Int J Clin Pediatr. 2017;6(1-2):8-19 doi: https://doi.org/10.14740/ijcp269w

Outcomes associated with antibiotic regimens for treatment of Mycobacterium abscessus in cystic fibrosis patients

Outcomes associated with antibiotic regimens for treatment of Mycobacterium abscessus in cystic fibrosis patients

Intralesional epidermal growth factor therapy fordiabetic foot ulcers: an evaluation of 15 cases

Background/aim: Intralesional recombinant epidermal growth factor (EGF) is a new treatment approach for diabetic foot ulcer, approved in 2006. EGF therapy is given as an adjunct to the standard treatment regimen of antibiotics, surgery, and hyperbaric oxygen. EGF accelerates the healing of diabetic foot ulcers and reduces healing time. This single-center study was conducted to evaluate the outcomes of intralesional EGF therapy in patients with diabetic foot ulcers.Materials and methods: We present the data of the follow-up patients treated in our clinics. Fifteen patients with diabetic foot ulcers or infections, who had been followed up and treated in our clinics, were included in this retrospective study. All patients were administered intralesional injections of 75 μg of EGF after treatment for infection on their diabetic foot ulcers, three times a week on alternate days. The patients were monitored with respect to treatment response and side effects of EGF.Results: Thirteen patients (86.7%) developed new granulation tissue, 10 patients (66.7%) had complete wound closure, and three patients (20%) showed partial wound closure. No serious side effects requiring discontinuation of EGF therapy were observed. A total of twenty-one bacterial agents were isolated in thirteen patients, and no bacterial growth was observed in the tissue cultures of two patients. Pseudomonas aeruginosa was the most common isolated infectious agent in the tissue cultures (n: 6, 28%). Conclusion: Intralesional injection of EGF on top of the standard treatment regimen appears to be a useful adjuvant therapy option in selected patients.

Glomerular and Tubular Renal Function after Repeated Once-Daily Tobramycin Courses in Cystic Fibrosis Patients.

Introduction. Antibiotic treatment regimens against Pseudomonas aeruginosa lung infection in cystic fibrosis (CF) patients often include aminoglycoside antibiotics that may cause chronic renal failure after repeated courses. Aminoaciduria is an early marker of acute aminoglycoside-induced renal tubular dysfunction. We hypothesized that urinary amino acid reabsorption is decreased after repeated once-daily tobramycin therapies. Methods. In this prospective cross-sectional study creatinine clearance was estimated by the Schwartz and the Cockcroft-Gault formula. Tubular amino acid reabsorption was determined by ion exchange chromatography in 46 patients with CF who received multiple tobramycin courses (6.3 ± 10.1 (1–57)) in a once-daily dosing regimen and 10 who did not. Results. Estimated creatinine clearance employing the Cockcroft-Gault was mildly reduced in 17/46 (37%) of the patients who received tobramycin and 5/10 (50%) of the patients who did not but in none using the Schwartz formula. No association with lifetime tobramycin courses was found. Tubular amino acid reabsorption was not influenced by the amount of once-daily tobramycin courses. Conclusion. Clinically not significant reduction of eCCL occurred in a minority of CF patients. However, chronic tubular dysfunction was not present in patients with CF repeatedly treated with tobramycin in the once-daily dosing scheme.

Simplified antibiotic regimens for treatment of clinical severe infection in the outpatient setting when referral is not possible for young infants in Pakistan (Simplified Antibiotic Therapy Trial [SATT]): a randomised, open-label, equivalence trial.

SummaryBackgroundParenteral antibiotic therapy for young infants (aged 0–59 days) with suspected sepsis is sometimes not available or feasible in countries with high neonatal mortality. Outpatient treatment could save lives in such settings. We aimed to assess the equivalence of two simplified antibiotic regimens, comprising fewer injections and oral rather than parenteral administration, compared with a reference treatment for young infants with clinical severe infection.MethodsWe undertook the Simplified Antibiotic Therapy Trial (SATT), a three-arm, randomised, open-label, equivalence trial in five communities in Karachi, Pakistan. We enrolled young infants (aged 0–59 days) who either presented at a primary health-care clinic or were identified by a community health worker with signs of clinical severe infection. We included infants who were not critically ill and whose family refused admission. We randomly assigned infants to either intramuscular procaine benzylpenicillin and gentamicin once a day for 7 days (reference); oral amoxicillin twice daily and intramuscular gentamicin once a day for 7 days; or intramuscular procaine benzylpenicillin and gentamicin once a day for 2 days followed by oral amoxicillin twice daily for 5 days. The primary outcome was treatment failure within 7 days of enrolment and the primary analysis was per protocol. We judged experimental treatments as efficacious as the reference if the upper bound of the 95% CI for the difference in treatment failure was less than 5·0. This trial is registered at ClinicalTrials.gov, number NCT01027429.FindingsBetween Jan 1, 2010, and Dec 26, 2013, 2780 infants were deemed eligible for the trial, of whom 2453 (88%) were enrolled. Because of inadequate clinical follow-up or treatment adherence, 2251 infants were included in the per-protocol analysis. 820 infants (747 per protocol) were assigned the reference treatment of procaine benzylpenicillin and gentamicin, 816 (751 per protocol) were allocated amoxicillin and gentamicin, and 817 (753 per protocol) were assigned procaine benzylpenicillin, gentamicin, and amoxicillin. Treatment failure within 7 days of enrolment was reported in 90 (12%) infants who received procaine benzylpenicillin and gentamicin (reference), 76 (10%) of those given amoxicillin and gentamicin (risk difference with reference −1·9, 95% CI −5·1 to 1·3), and 99 (13%) of those treated with procaine benzylpenicillin, gentamicin, and amoxicillin (risk difference with reference 1·1, −2·3 to 4·5).InterpretationTwo simplified antibiotic regimens requiring fewer injections are equivalent to a reference treatment for young infants with signs of clinical severe infection but without signs of critical illness. The use of these simplified regimens has the potential to increase access to treatment for sick young infants who cannot be referred to hospital.FundingThe Saving Newborn Lives initiative of Save the Children, through support from the Bill & Melinda Gates, and by WHO and USAID.