Sequential Antibiotic Therapy Research Articles

Comparison of the Efficacy of Two-Week Vonoprazan Versus Lansoprazole-Based Quadruple Sequential Antibiotic Therapy in Eradicating Helicobacter pylori Infection: A Non-randomized Clinical Trial.

The prevalence of Helicobacter pylori is escalating in developing countries, exacerbated by unjustified antibiotic usage, which leads to increased resistance. This trend has been notably amplified since the COVID-19 pandemic. Consequently, the effectiveness of existing eradication regimens has been compromised. This study aimed to compare the efficacy of two weeks of vonoprazan-based quadruple sequential therapy and lansoprazole-based quadruple sequential therapy in treating H. pylori infection. Methods: A non-randomized clinical trial was conducted over 18 months at the Department of Gastroenterology, Lahore General Hospital, Lahore, Pakistan. It included patients presenting with dyspepsia, as defined by the Rome IV criteria, and who tested positive on the urea breath test. Patients were divided into two groups, i.e., Group A and Group B. Group A patients received lansoprazole 30 mg + amoxicillin + tinidazole + tab. colloidal bismuth subcitrate for the first seven days, followed by lansoprazole + levofloxacin + azithromycin + colloidal bismuth subcitrate. Group B patients received vonoprazan + amoxicillin + tinidazole + colloidal bismuth subcitrate for the first seven days, followed by vonoprazan + levofloxacin + azithromycin + colloidal bismuth subcitrate. Both regimes continued for 14 days. Four weeks after 14 days of the treatment, an early morning urea breath test was conducted to evaluate the efficacy of the treatment. Patients were scheduled for follow-up visits at seven and 14 days post-treatment initiation to record adverse events and assess compliance with the treatment regimen. Patients who lost the follow-up and remained non-compliant to the medications were excluded from the final data analysis as per standard protocols of the per-protocol analysis. Results: A total of 252 patients were included. In Group A and Group B, 6/126 (4.76%) and 8/126 (6.35%) of the patients were lost to follow-up, respectively. The non-compliance rate in Group A was 5/126 (3.97%), compared to Group B with 3/126 (2.38%). Finally, the per-protocol analysis of the resultsincluded 115 patients in each group. Baseline characteristics, including demographics, lifestyle, and clinical factors, were comparable between groups with p-values of 0.138 for age, 0.356 for gender, 0.126 for BMI, 0.495 for residence, 0.500 for water source, 0.866 for meal habit, 0.863 for smoking, 0.188 for nonsteroidal anti-inflammatory drug(NSAID) use, 0.145 for proton pump inhibitor(PPI) use, 0.213 for antibiotics, and 0.456 for treatment history. Both treatments effectively eradicated H. pylori, as determined by a negative urea breath test at four weeks post-treatment, with Group B showing a higher eradication rate of 96.5% compared to 92.2% in Group A, although the difference was not statistically significant (p = 0.153).There was no difference in adverse effects in both treatment groups (p-value > 0.05). Conclusion: The study found that while the vonoprazan-based regime exhibited a slightly higher eradication rate of H. pylori compared to lansoprazole, the difference was not statistically significant. It was concluded that both regimens demonstrated comparable efficacy and similar profiles of adverse effects in treating H. pylori infection.

Fitness Costs of Antibiotic Resistance Impede the Evolution of Resistance to Other Antibiotics.

Antibiotic resistance is a major threat to global health, claiming the lives of millions every year. With a nearly dry antibiotic development pipeline, novel strategies are urgently needed to combat resistant pathogens. One emerging strategy is the use of sequential antibiotic therapy, postulated to reduce the rate at which antibiotic resistance evolves. Here, we use the soft agar gradient evolution (SAGE) system to carry out high-throughput in vitro bacterial evolution against antibiotic pressure. We find that evolution of resistance to the antibiotic chloramphenicol (CHL) severely affects bacterial fitness, slowing the rate at which resistance to the antibiotics nitrofurantoin and streptomycin emerges. In vitro acquisition of compensatory mutations in the CHL-resistant cells markedly improves fitness and nitrofurantoin adaptation rates but fails to restore rates to wild-type levels against streptomycin. Genome sequencing reveals distinct evolutionary paths to resistance in fitness-impaired populations, suggesting resistance trade-offs in favor of mitigation of fitness costs. We show that the speed of bacterial fronts in SAGE plates is a reliable indicator of adaptation rates and evolutionary trajectories to resistance. Identification of antibiotics whose mutational resistance mechanisms confer stable impairments may help clinicians prescribe sequential antibiotic therapies that are less prone to resistance evolution.

Comparison of the efficacies of triple, quadruple and sequential antibiotic therapy in eradicating Helicobacter pylori infection: A randomized controlled trial.

There is regional variation in the eradication rates of Helicobacter pylori (H. pylori) regimens depending on the local antibiotic resistance patterns. The aim of this study was to compare the efficacies of triple, quadruple and sequential antibiotic therapy in eradicating H. pylori infection. A total of 296 H. pylori-positive patients were randomized to receive one of the three regimens (triple, quadruple or sequential antibiotic therapy) and eradication rate was assessed by H. pylori stool antigen test. The eradication rates of standard triple therapy, sequential therapy and quadruple therapy were 93%, 92.9% and 96.4%, respectively (p = 0.57). Fourteen days of standard triple therapy, 14 days of bismuth-based quadruple therapy and 10 days of sequential therapy are equally efficacious in eradicating H. pylori and all regimens have optimum H. pylori eradication rates. ClinicalTrials.gov Identifier: CTRI/2020/04/024929.

Sequential antibiotic therapy in the laboratory and in the patient.

Laboratory experiments suggest that rapid cycling of antibiotics during the course of treatment could successfully counter resistance evolution. Drugs involving collateral sensitivity could be particularly suitable for such therapies. However, the environmental conditions in vivo differ from those in vitro. One key difference is that drugs can be switched abruptly in the laboratory, while in the patient, pharmacokinetic processes lead to changing antibiotic concentrations including periods of dose overlaps from consecutive administrations. During such overlap phases, drug-drug interactions may affect the evolutionary dynamics. To address the gap between the laboratory and potential clinical applications, we set up two models for comparison-a 'laboratory model' and a pharmacokinetic-pharmacodynamic 'patient model'. The analysis shows that in the laboratory, the most rapid cycling suppresses the bacterial population always at least as well as other regimens. For patient treatment, however, a little slower cycling can sometimes be preferable if the pharmacodynamic curve is steep or if drugs interact antagonistically. When resistance is absent prior to treatment, collateral sensitivity brings no substantial benefit unless the cell division rate is low and drug cycling slow. By contrast, drug-drug interactions strongly influence the treatment efficiency of rapid regimens, demonstrating their importance for the optimal choice of drug pairs.

TREATMENT OF COMBINED ACNE AND GENITOURINARY INFECTIONS CAUSED BY CHLAMYDIA AND MYCOPLASMAS.

The aim: To substantiate, develop and apply in clinical practice a method for the treatment of combined acne and genitourinary infections caused by chlamydia and mycoplasmas. Materials and methods: Acne was diagnosed clinically. Chlamydia trachomatis; Mycoplasma genitalium; Mycoplasma hominis; Ureaplasma urealyticum were identified using polymerase chain reaction. 30 patients with combined acne and urogenital chlamydia and/or mycoplasmas received sequential oral antibiotic therapy with josamycin (1500 mg daily) and gatifloxacin (400 mg daily) for 10 days each. Simultaneously with antibiotic therapy, concomitant symptomatic and topical treatment was provided. Results: The elimination of pathogens of urogenital chlamydia and/or mycoplasmas was achieved with 29 out of 30 patients (93.3%). At the same time a complete regression of facial rash inflammatory elements was detected at 18 (60%) treated patients, while with the remaining 12 (40%) the regression was significant. Conclusions: Antibiotic therapy was used in the treatment for both acne and urogenital chlamydia and/or mycoplasmas. An original method of complex treatment of combined acne and urogenital chlamydia and/or mycoplasmas was substantiated, developed and successfully applied. The offered method of treatment can be considered as a proof of high effectiveness both for elimination of pathogens from the genitourinary system of patients, and for complete or significant elimination of inflammatory facial rash.

Prophylactic sequential antibiotic therapy for recurrent liver/biliary sepsis

Background and AimsRecurrent liver/biliary sepsis are rare and can occur in different situations. Curative treatment of acute septic episodes is based on antibiotics. Nevertheless, recurrent sepsis can be life-threatening, and the treatment of the underlying disease could be complex, and eventually not possible. The aim of the present study was to report our experience on prophylactic sequential antibiotic therapy for recurrent liver/biliary sepsis in a large cohort of patients with long follow-up. MethodsAll patients who received a prophylactic sequential antibiotic therapy for recurrent liver/biliary sepsis in our institution from 2005 to 2020 were included. Prophylactic sequential antibiotic therapy was based on per os antibiotics with expected antibacterial activity on digestive bacteria, mainly Gram-negative bacilli. The primary end-point was the reduction of the number of septic episodes to 1 or less episode per year, and not severe (not requiring hospitalization). ResultsWere included 33 adult patients and the main initial disease/condition leading to prophylaxis was history of hepaticojejunostomy (78.8%). The majority of septic episodes required hospitalization (57.6%). First line prophylactic sequential antibiotic therapy was weekly ciprofloxacin in all cases. First line therapy was successful in the long-term in 19 patients (57.6%), with a median follow-up of 92 months (range: 25-206). Global efficacy (first-second-third lines) was 28/33 (84.8%). ConclusionsThe results of the present study with very long follow-up suggest that prophylactic sequential antibiotic therapy can successfully prevent recurrent liver/biliary sepsis with good tolerance.

Role of cefuroxime as antibiotic prophylaxis for general surgery: An expert opinion

Surgical site infections (SSIs) are serious postoperative complications reported globally, which lead to perioperative antibiotics use during routine practice in surgical procedures. Selection of appropriate antibiotic/s for prophylaxis is a vital step in the management and care of invasive surgical procedures. This expert opinion review was developed based on expert discussion and literature search on scientific databases with special emphasis on cefuroxime in surgical prophylaxis for general surgeries. Cephalosporins are globally considered to be the drugs of choice for surgical prophylaxis in general surgeries owing to good safety, bactericidal activity, penetration to critical tissues, and proven efficacy in clinical trials. Cefuroxime, a 2nd generation cephalosporin, is an effective, safe and low-cost antibiotic for surgical prophylaxis in general surgeries, in particular for patients who need sequential antibiotic therapy. Cefuroxime can be administered alone or in combination with other classes of antibiotics based on clinical characteristics of individual patients and surgeon’s discretion to reduce the risk of postoperative SSIs, abscess, septicemia, and microbial growth.Cefuroxime can be administered alone or in combination with other classes of antibiotics based on clinical characteristics of individual patients and surgeon’s discretion to reduce the risk of postoperative SSIs, abscess, septicemia, and microbial growth.

Efficacy and safety of decamethoxin in complex treatment of patients with group III viral-bacterial community-acquired pneumonia

BACKGROUND. There are many unsolved medical problems and, of course, pneumonia is one of them. Communityacquired pneumonia (CAP) is a multifactorial disease, but the role of viruses as causative agents is constantly growing. Specific antiviral therapy for CAP is limited. Therefore, the search for drugs with virucidal activity remains relevant. An antimicrobial agent with a broad spectrum of action – decamethoxin – is successfully used today for treatment of patients with infectious exacerbations of bronchial asthma and chronic bronchitis. At the same time efficacy of decamethoxin in CAP patients was not studied. OBJECTIVE. To evaluate the effectiveness and safety of the inhaled antimicrobial drug decamethoxin in the complex treatment of patients with group III viral-bacterial CAP. MATERIALS AND METHODS. There was enrolled 62 patients with group III viral-bacterial CAP. All patients received the same sequential antibiotic therapy: protected aminopenicillin with macrolide or III generation cephalosporin with macrolide. Patients of the main group were prescribed inhalations through a nebulizer of the antiseptic drug decamethoxin in addition to antibacterial therapy from the first day of treatment for 5-7 days. RESULTS AND DISCUSSION. No adverse events were detected in any of the patients during treatment. In all cases, recovery was diagnosed. At the same time, the term of achieving positive results in the main group was 12.2±0.7 days, and in the control – 17.2±0.7 (р <0,05). The average duration of antibiotic use was different in main and control groups: respectively 9.4±0.4 and 10.7±0.4 days (р <0,05). There were no infectious complications in the patients of the main group, while 24 (72 %) patients of the control group were diagnosed with acute rhinopharyngitis (47.0 % of cases), lateral pharyngitis (13 %) and sinusitis (9 %), other complications (otitis, infectious exudative pericarditis). In 22 (66 %) cases there was one complication and in 2 (6 %) cases there were two complications. CONCLUSIONS. For patients with group III viral-bacterial CAP additional inclusion in the empirical sequential antibiotic therapy of inhaled decamethoxin can significantly reduce the frequency of infectious complications, duration of antibiotic therapy, as well as the duration of positive treatment results.

The benefits and safety of oral sequential antibiotic therapy in non-complicated and complicated Staphylococcus aureus bacteremia

BackgroundTreatment optimization for serious infections, such as Staphylococcus aureus bacteremia (SAB), is a challenge for antimicrobial stewardship teams. Currently, SAB guidelines recommend a completely intravenous therapy (CIT). ObjectivesThe objective of the study was to analyze the usefulness and safety of oral sequential therapy (OST) in SAB. Patients and methodsWe conducted a retrospective, observational study in a tertiary teaching hospital in Spain. The inclusion criteria were complicated and non-complicated monomicrobial SAB and an adequate duration of therapy, with patients classified into OST or CIT. The primary endpoint was the 90-day recurrence of S. aureus infection. We also analyzed the mortality, the length of the hospital stay, and the duration of the intravenous antibiotic administration. ResultsOf a total of 201 patients with SAB, 125 (62%) underwent OST. The most commonly administered oral antibiotic was trimethoprim-sulfamethoxazole (66% of patients). Of those administered OST, 43% had complicated bacteremia (most with an osteoarticular source of infection), and 6% had an intravascular device. The 90-day recurrence rate was 4%, with no differences between the two groups. The duration of the therapy (22 [16–28] vs. 13 days [8–17] for CIT and OST, respectively; p < 0.001) and the hospital stay (36 [27–71] vs. 18 days [13–29] for CIT and OST, respectively; p < 0.001) were shorter for OST. MRSA was related with mortality (OR 4.4, 95% CI [1.67−11.37]; p = 0.003). ConclusionsOST for properly selected patients with SAB could be a safe therapeutic option and can reduce their use of CIT and their hospital stay.

Study of Small Intestinal Bacterial Overgrowth in a Cohort of Patients with Abdominal Symptoms Who Underwent Bariatric Surgery.

Small intestinal bacterial overgrowth (SIBO) is a common complication of bariatric surgery. Digestive decontamination treatments with oral antibiotic therapy vary and are not codified. This retrospective study was conducted to analyse the characteristics of bariatric surgery patients who underwent a glucose breath test (GBT) and to analyse the effectiveness of the antibiotic decontamination therapy. A total of 101 operated patients (Roux-en-Y bypass (RYB), omega bypass (ΩB) and sleeve gastrectomy (SG)) who underwent a GBT (75g/250mL) were included. Anthropometric data, symptoms of SIBO, type of surgery, use of proton pump inhibitors (PPIs) and antibiotic therapy were analysed. The effectiveness of the antibiotic treatment, defined by improvement of the symptoms, was evaluated during the follow-up. Of the 85 women and 16 men included (48.5 ± 3.6years old), 63 underwent RYB, 31 underwent ΩB and 7 underwent SG. The GBT was positive in 83% of the patients. A positive test was associated with age (p < 0.001), female sex (p < 0.01) and PPI use (p < 0.01), but there was no significant difference according to the type of surgery. Sixty-one percent of patients treated with gentamicin/metronidazole sequential antibiotic therapy and 58% of patients treated with metronidazole alone achieved treatment efficacy (with no significant difference in efficacy between these treatments). SIBO should be systematically considered in the context of abdominal symptoms in bariatric surgery patients, regardless the type of surgery, particularly in patients who are older or female and after PPI treatment. Digestive decontamination appears to be similar between gentamycin/metronidazole and metronidazole treatments.

Clinical outcome of extended trochanteric osteotomy in two-stage revision of periprosthetic hip infection

Objective To investigate the efficacy of using an extended trochanteric osteotomy as part of a two-stage exchange procedure for periprosthetic hip infection. Methods We retrospectively analyzed 16 patients (16 hips) including 9 males and 7 females who had extended trochanteric osteotomy as part of two-stage revision procedure for periprosthetic hip infection from January 2008 to January 2012, the average age was 65.2±6.4 years at the time of operation. The two-stage revision protocol included taking out of all implants using extended trochanteric osteotomy, meticulous debridement, restoration of the osteotomies and fixed with cerclage wiring, implantation of antibiotic bone cement spacer in first stage. After sequential therapy of antibiotics through peripheral vein and enteral prescription, the prosthesis was implanted in the second stage. Harris hip score was used to evaluate the hip function. X-ray radiograph was conducted to evaluate the healing of osteotomy, eradication of infection, prosthesis stability, displacement and looseness. Results All patients were followed-up for 24-90 months (53.4±7.2 months on the average). The interval between the first and second surgery was 8.6±2.1 months with a range from 5-18 months. All osteotomies healed uneventfully, with the average heal time 13.2 ± 1.3 weeks (range from 8 to 16 weeks). The infection was eradicated in 15 hips (93.8%) at the second surgery. One hip with staphylococcus epidermidis infection was confirmed by bacterial culture of synovial fluid in second surgery. Infection symptom disappeared after sequential antibiotic therapy. At the last follow-up, all patients had successful eradication of infection, with Harris score improved from 38.6 ± 5.4 preoperatively to 86.4 ± 3.2. Thirteen patients achieved bone ingrowths, while the other 3 patients had fibrous ingrowths. Two cases had intraoperative fracture, 2 had postoperative spacer dislocation. Conclusion Extended trochanteric osteotomy as part of a two-stage exchange arthroplasty can be performed safely and effectively in periprosthetic hip infection, with reliable osteotomy healing. Furthermore, it does not influence the effects of infection treatment and component stability. Key words: Arthroplasty, replacement, hip; Osteotomy; Prosthesis-related infections; Reoperation

Sequential (as Opposed to Simultaneous) Antibiotic Therapy Improves Helicobacter pylori Eradication in the Pediatric Population: A Meta-Analysis.

Helicobacter pylori is a common infection associated with many gastrointestinal diseases. Triple or quadruple therapy is the current recommendation for H pylori eradication in children but is associated with success rates as low as 50%. Recent studies have demonstrated that a 10-day sequential therapy regimen, rather than simultaneous antibiotic administration, achieved eradication rates of nearly 95%. This meta-analysis found that sequential therapy increased eradication rates by 14.2% (relative risk [RR] = 1.142; 95% confidence interval [CI] = 1.082-1.207; P < .001). Ten-day sequential therapy significantly improved H pylori eradication rates compared to the 7-day standard therapy (RR = 1.182; 95% CI = 1.102-1.269; p < .001) and 10-day standard therapy (RR = 1.179; 95% CI = 1.074-1.295; P = .001), but had lower eradication rates compared to 14-day standard therapy (RR = 0.926; 95% CI = 0.811-1.059; P = .261). The use of sequential therapy is associated with increased H pylori eradication rates in children compared to standard therapy of equal or shorter duration.

Su1140 Sequential (As Opposed to Simultaneous) Antibiotic Therapy Improves Helicobacter pylori Eradication in the Pediatric Population: A Meta-Analysis

Su1140 Sequential (As Opposed to Simultaneous) Antibiotic Therapy Improves Helicobacter pylori Eradication in the Pediatric Population: A Meta-Analysis

Optimizing antibiotic therapy of group IV community-acquired pneumonia patients.

The aim of the study was to evaluate the clinical and economical effectiveness of differentiated antibacterial therapy of group IV patients with community-acquired pneumonia (CAP). Materials and methods. 42 patients, admitted to the hospital with severe CAP without risk factors for P. aeruginosa infection were randomized in three groups in 1:1:1 ratio. All patients received sequential antibacterial therapy with i.v. amoxicillin/clavulanate or ceftriaxone, or ertapenem in combination with azithromycin switched to oral amoxicillin/clavulanate, cefuroxime axetil in combination with oral azithromycin or levofloxacin, respectively, after initial improvement in 3–4 days. A comparative effectiveness analysis was performed based on clinical, laboratory and economic data. Results. Treatment outcomes in all subgroups of patients were similar: in 1st subgroup the cure rate was (28,6 ± 12,1) %, improvement – in (49,4 ± 13,2) % of patients; in 2nd and 3rd subgroups the cure/improvement rates were (35,7 ± 12,8) and (42,9± 13,2) %, respectively (р > 0,05). Conclusion. Antibacterial therapy, always empiric and differentiated depending on severity of disease, con­comitant conditions and previous use of antibiotics within 3 months of the onset of the disease, is a milestone of treatmet of CAP patients. A sequential antibiotic therapy with either aminopenicillin (amoxicillin/clavulanate) of 3rd generation cephalosporin (ceftriaxone/cefuroxime axetil) in combination with macrolide (azithromycin) or carbapenem (ertapenem, followed by levofloxacin) is recommended in hospitalized clinical group IV CAP patients without risk factors for P. aeruginosa infection. In current group of patients pharmacoeconomic analysis confirmed the expediency of administration a sequential antibiotic therapy with parenteral amoxicillin/clavulanat or ceftriaxone in combination with azithromycin, followed by oral amoxicillin/clavulanat or cefuroxime axetil in combination with azithromycin upon stabilization of patient’s condition.

Minimally invasive endoscopic treatment for lumbar infectious spondylitis: a retrospective study in a tertiary referral center

BackgroundSpinal infections remain a challenge for clinicians because of their variable presentation and complicated course. Common management approaches include conservative administration of antibiotics or aggressive surgical debridement. The purpose of this study was to evaluate the efficacy of percutaneous endoscopic debridement with dilute betadine solution irrigation (PEDI) for treating patients with lumbar infectious spondylitis.MethodsFrom January 2005 to July 2010, a total of 32 patients undergoing PEDI were retrospectively enrolled in this study. The surgical indications of the enrolled patients included single-level infectious spondylodiscitis, postoperative infectious spondylodiscitis, advanced infection with epidural abscess, psoas muscle abscess, pre-vertebral or para-vertebral abscess, multilevel infectious spondylitis, and recurrent infection after anterior debridement and fusion. Clinical outcomes were assessed by careful physical examination, Macnab criteria, regular serologic testing, and imaging studies to determine whether continued antibiotics treatment or surgical intervention was required.ResultsCausative bacteria were identified in 28 (87.5%) of 32 biopsy specimens. Appropriate parenteral antibiotics for the predominant pathogen isolated from infected tissue biopsy cultures were prescribed to patients. Twenty-seven (84.4%) patients reported satisfactory relief of their back pain after PEDI. Twenty-six (81.3%) patients recovered uneventfully after PEDI and sequential antibiotic therapy. No surgery-related major complications were found, except 3 patients with transient paresthesia in the affected lumbar segment.ConclusionsPEDI was successful in obtaining a bacteriologic diagnosis, relieving the patient’s symptoms, and assisting in the eradication of lumbar infectious spondylitis. This procedure could be an effective alternative for patients who have a poor response to conservative treatment before a major open surgery.

Impact of an intervention in the use of sequential antibiotic therapy in a Brazilian university hospital

Sequential antibiotic therapy (SAT) is safe and economical. However, the unnecessary use of intravenous (IV) administration usually occurs. The objective of this work was to get to know the effectiveness of an intervention to implement the SAT in a teaching hospital in Brazil. This was a prospective and interventional study, historically controlled, and was conducted in the Hospital de Clínicas, Universidade Federal de Uberlândia, State of Minas Gerais, Brazil, a high complexity teaching hospital having 503 beds. In each of the periods, from 04/04/05 to 07/20/05 (pre-intervention) and from 09/24/07 to 12/20/07 (intervention), 117 patients were evaluated. After the pre-intervention period, guidelines were developed which were implemented during the intervention period along with educational measures and a reminder system added to the patients' prescription. In the pre-intervention and intervention periods, the IV antibiotics were used as treatment for a average time of 14.8 and 11.8 days, respectively. Ceftriaxone was the antibiotic most prescribed in both periods (23.4% and 21.6% respectively). Starting from the first prescription of antibiotics, the average length of hospitalization time was 21.8 and 17.5 days, respectively. The SAT occurred only in 4 and 5 courses of treatment, respectively, and 12.8% and 18.8% of the patients died in the respective periods. Under the presented conditions, the evaluated intervention strategy is ineffective in promoting the exchange of the antibiotic administration from IV to oral treatment (SAT).

Diffuse duodenal nodular lymphoid hyperplasia: a large cohort of patients etiologically related to Helicobacter pyloriinfection

BackgroundNodular lymphoid hyperplasia of gastrointestinal tract is a rare disorder, often associated with immunodeficiency syndromes. There are no published reports of its association with Helicobacter pylori infection.MethodsFrom March 2005 till February 2010, we prospectively followed all patients with diffuse duodenal nodular lymphoid hyperplasia (DDNLH). Patients underwent esophagogastroduodenoscopy with targeted biopsies, colonoscopy, and small bowel video capsule endoscopy. Duodenal nodular lesions were graded from 0 to 4 based on their size and density. Patients were screened for celiac sprue (IgA endomysial antibody), immunoglobulin abnormalities (immunoglobulin levels & serum protein electrophoresis), small intestine bacterial overgrowth (lactulose hydrogen breath test), and Helicobacter pylori infection (rapid urease test, and histological examination of gastric biopsies). Patients infected with Helicobacter pylori received sequential antibiotic therapy and eradication of infection was evaluated by 14C urea breath test. Follow up duodenoscopies with biopsies were performed to ascertain resolution of nodular lesions.ResultsForty patients (Males 23, females 17; mean age ± 1SD 35.6 ± 14.6 years) with DDNLH were studied. Patients presented with epigastric pain, vomiting, and weight loss. Esophagogastroduodenoscopy showed diffuse nodular lesions (size varying from 2 to 5 mm or more) of varying grades (mean score ± 1SD 2.70 ± 0.84) involving postbulbar duodenum. Video capsule endoscopies revealed nodular disease exclusively limited to duodenum. None of the patients had immunoglobulin deficiency or small intestine bacterial overgrowth or positive IgA endomysial antibodies. All patients were infected with Helicobacter pylori infection. Sequential antibiotic therapy eradicated Helicobacter pylori infection in 26 patients. Follow up duodenoscopies in these patients showed significant reduction of duodenal nodular lesions score (2.69 ± 0.79 to 1.50 ± 1.10; p < 0.001). Nodular lesions showed complete resolution in 5 patients and significant resolution in remaining 21 patients. Patients with resistant Helicobacter pylori infection showed no significant reduction of nodular lesions score (2.71 ± 0.96 to 2.64 ± 1.15; p = 0.58). Nodules partially regressed in score in 2 patients, showed no interval change in 10 patients and progressed in 2 patients.ConclusionsWe report on a large cohort of patients with DDNLH, etiologically related to Helicobacter pylori infection.

Sequential antibiotic therapy in the treatment of hospitalized children with community-acquired pneumonia

Objective: Evaluate the efficacy, time and the cost of hospitalization using sequential therapy (short IV course + oral antibiotics) in hospitalized children with community acquire bacterial pneumonia without pleural effusion and compared to conventional IV therapy. Methods: Prospective, randomized, open trial, admitting patients with community acquire bacterial pneumonia that fulfilled all the following criteria: (1) Toxemia; (2) Fever 38°C; (3) Abnormal physical exam; (4) Blood leukocytes >15,000); (5) PCR 48mg/l; (6) Chest X-Ray compatible with bacterial infection. Patients were excluded if they had wheezing on chest auscultation or had any associated systemic disease. On admission, patient severity was documented by Pediatric Risk of Mortality score (PRISM). Patients were randomized to conventional treatment (group C) or sequential treatment (group S). Children 3 month to six years old received intravenous ampycillin and those older than six years intravenous penicillin G. Patients in group C received IV therapy for 10 days or after 24 hours without fever. In group S, oral replaced IV antibiotic when at least three out of six clinical admission criteria improved. Results: 258 patients were analyzed, 130 of then (50.4%) in group C and 128 (49.6%) in group S. There was no difference between both groups, in relation of age, sex, onset of symptoms, (PRISM) score, and previous use of ATB. The time of IV ATB was significantly shorter in group S (3 versus 4 days; p < 0,001) There was a direct correlation with PRISM score and number of days hospitalized. Time of hospitalization were significantly decreased in group S (5 versus 6 days p < 0.01) with hospital cost 19.7% lower when compared with group C (p < 0,02). There was no difference in treatment failure between the two groups (p = 0.48). Conclusion: Our study suggests that bacterial pneumonia treatment using oral sequential ATB is safe and effective when compare with prolonged IV antibiotic treatment, with shorter hospitalization time and lower cost.

Acute septic arthritis revisited: a prospective study in 93 patients correlating C-reactive protein levels with duration of intravenous antibiotic therapy, clinical and radiological outcomes

Septic arthritis is the most dreaded affection of the joints in children. Early diagnosis, urgent arthrotomy and intravenous antibiotic therapy, however, are essential factors in treatment of septic arthritis to prevent devastating complications. However, the optimal duration of intravenous antibiotic therapy for acute septic arthritis after surgical drainage is not well defined. We performed a prospective study in 93 patients with age less than 5 years who presented with acute septic arthritis and treated with arthrotomy and sequential antibiotic therapy based on determination of serial quantitative CRP levels correlating radiological and clinical outcome. Majority of the subjects (84%) had CRP values more than or equal to 96 mg/dl at the time of presentation. More than half of the subjects had CRP values reverted to normal by the seventh day of treatment. By the 21st day of treatment, all the subjects had CRP values at baseline levels. “The clinical and radiological outcome was excellent in 85% of the cases where the CRP normalized by 7 days compared to 25% where the CRP had not normalized by 21 days.” The difference was found to be statistically significant. We conclude from our study that CRP levels decreases consistently during the antibiotic therapy and patients in whom CRP values return to normal earlier have good clinical and radiological outcomes. We also conclude that intravenous antibiotics should be stopped and switched over to oral therapy once CRP levels return to normal in cases of acute septic arthritis.

The Impact of Different Antibiotic Regimens on the Emergence of Antimicrobial-Resistant Bacteria

BackgroudThe emergence and ongoing spread of antimicrobial-resistant bacteria is a major public health threat. Infections caused by antimicrobial-resistant bacteria are associated with substantially higher rates of morbidity and mortality compared to infections caused by antimicrobial-susceptible bacteria. The emergence and spread of these bacteria is complex and requires incorporating numerous interrelated factors which clinical studies cannot adequately address.Methods/Principal FindingsA model is created which incorporates several key factors contributing to the emergence and spread of resistant bacteria including the effects of the immune system, acquisition of resistance genes and antimicrobial exposure. The model identifies key strategies which would limit the emergence of antimicrobial-resistant bacterial strains. Specifically, the simulations show that early initiation of antimicrobial therapy and combination therapy with two antibiotics prevents the emergence of resistant bacteria, whereas shorter courses of therapy and sequential administration of antibiotics promote the emergence of resistant strains.Conclusions/SignificanceThe principal findings suggest that (i) shorter lengths of antibiotic therapy and early interruption of antibiotic therapy provide an advantage for the resistant strains, (ii) combination therapy with two antibiotics prevents the emergence of resistance strains in contrast to sequential antibiotic therapy, and (iii) early initiation of antibiotics is among the most important factors preventing the emergence of resistant strains. These findings provide new insights into strategies aimed at optimizing the administration of antimicrobials for the treatment of infections and the prevention of the emergence of antimicrobial resistance.