Quality of care for children with severe disease in the Democratic Republic of the Congo

By Clarke-Deelder E, Shapira G, Samaha H, Fritsche GB, Fink G

BMC Public Health, December 2,  2019

 

Despite the almost universal adoption of Integrated Management of Childhood Illness (IMCI) guidelines for the diagnosis and treatment of sick children under the age of five in low- and middle-income countries, child mortality remains high in many settings. One possible explanation of the continued high mortality burden is lack of compliance with diagnostic and treatment protocols. We test this hypothesis in a sample of children with severe illness in the Democratic Republic of the Congo (DRC).

 

Continue reading
50 Hits
0 Comments

Effect of co-trimoxazole prophylaxis on morbidity and mortality of HIV-exposed, HIV-uninfected infants in South Africa: a randomised controlled, non-inferiority trial

By Brodie Daniels, Anna Coutsoudis, Eshia Moodley-Govender, Helen Mulol, Elizabeth Spooner, Photini Kiepiela, et al.

The Lancet Global Health, December, 2019

WHO guidelines recommend co-trimoxazole prophylaxis for HIV-exposed, HIV-uninfected infants. These guidelines date back to an era in which HIV testing of infants was impossible and mothers had poor access to antiretroviral treatment. To determine whether this guideline requires revision in the current era of effective prevention of mother-to-child transmission and early infant diagnosis programmes, we aimed to investigate whether receiving no co-trimoxazole prophylaxis is inferior to receiving co-trimoxazole prophylaxis in the resulting incidence of grade 3 or 4 common childhood illnesses or mortality in breastfed HIV-exposed, HIV-uninfected infants.

We screened 1570 mother–child pairs for study enrolment, from whom (78%) eligible infants were enrolled into the study between Oct 16, 2013, and May 23, 2018. Of the infants enrolled, 611 (50%) were randomly assigned to the co-trimoxazole group and 609 (50%) were randomly assigned to the no co-trimoxazole group. One (<1%) infant in the no co-trimoxazole group was excluded from the analysis of the final outcomes for having received traditional medicine (which only became apparent after randomisation); therefore, 611 (50%) infants in the co-trimoxazole group and 608 (50%) infants in the no co-trimoxazole group were included in the final intention-to-treat analysis. 136 (22%) infants in the co-trimoxazole group and 139 (23%) infants in the no co-trimoxazole group did not complete the 12-month study visit, predominantly because of loss to follow-up (93 [15%] infants in the co-trimoxazole group; 90 [15%] infants in the no co-trimoxazole group). The cumulative probability of the composite primary outcome was 0·114 (95% CI 0·076 to 0·147; 49 events) in the co-trimoxazole group versus 0·0795 (0·044 to 0·115; 39 events) in the no co-trimoxazole group. The risk difference (no co-trimoxazole group minus co-trimoxazole group) was −0·0319 (–0·075 to 0·011), meaning that the risk was around 3 percentage points lower in the no co-trimoxazole group on the additive scale.

Access article here.

53 Hits
0 Comments

Ambulatory Antibiotic Prescribing for Children with Pneumonia After Publication of National Guidelines: A Cross-Sectional Retrospective Study

 By Poole, N.M., Shapiro, D.J., Kronman, M.P. et al.

Infectious Diseases and Therapy, November 27, 2019.

National guidelines published in 2011 recommend amoxicillin as first-line treatment for non-hospitalized children with community-acquired pneumonia (CAP). We aimed to understand visit rates, antibiotic selection, and factors associated with amoxicillin prescribing for children with CAP since guideline publication.

We performed a cross-sectional retrospective study of patients aged 90 days–18 years with an outpatient clinic or emergency department (ED) visit from 2008 to 2015 using the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey ED data files, respectively. We estimated the incidence rates of ambulatory CAP visits, examined time trends in antibiotics prescribed at CAP visits, and determined factors independently associated with first-line guideline-recommended antibiotic prescribing using multivariable logistic regression, including patient age, setting, and US census region.

 

Continue reading
44 Hits
0 Comments

Survival benefit associated with clarithromycin in severe community-acquired pneumonia: A matched comparator study

By Evdoxia Kyriazopoulou, Dimitrios Sinapidis, Stamatios Halvatzis, Dimitrios Velissaris, Nikolaos Alexiou, Vasilios Kosmase, Maria Evangelia Adami,  Miltiades Kyprianou,  Aikaterini Kyprianou,  Aggelos Stefos,  Malvina Lada, et al.

 

International Journal of Antimicrobial Agents, November 5, 2019

 

Although analysis of retrospective studies has documented survival benefit from the addition of a macrolide to the treatment regimen for community-acquired pneumonia (CAP), no data are available to determine if there is differential efficacy between members of the macrolide family. In order to investigate this, an analysis was undertaken of data from 1174 patients with CAP who met the new Sepsis-3 definitions and were enrolled prospectively in the data registry of the Hellenic Sepsis Study Group. Four well-matched treatment groups were identified with 130 patients per group: clarithromycin and β-lactam; azithromycin and β-lactam; respiratory fluoroquinolone and β-lactam monotherapy. The primary endpoint was comparison of the effects of clarithromycin with β-lactam monotherapy on 28-day mortality. The secondary endpoint was resolution of CAP. Mortality rates for the clarithromycin, azithromycin, respiratory fluoroquinolone and β-lactam groups were 20.8%, 33.8% (P=0.026 vs clarithromycin), 32.3% (P=0.049 vs clarithromycin) and 36.2% (P=0.009 vs clarithromycin), respectively. After stepwise Cox regression analysis among all groups, clarithromycin was the only treatment modality associated with a favourable outcome (hazard ratio 0.61; P=0.021). CAP resolved in 73.1%, 65.9% (P=0.226 vs clarithromycin), 58.5% (P=0.009 vs clarithromycin) and 61.5% (P=0.046 vs clarithromycin) of patients, respectively. It is concluded that the addition of clarithromycin to the treatment regimen of patients with severe CAP leads to better survival rates.

Continue reading
45 Hits
0 Comments

The Impact of the Duration of Antibiotic Therapy in Patients With Community-Onset Pneumonia on Readmission Rates: A Retrospective Cohort Study

By Daniel M. Parshall, Julia E. Sessa, Kelly M. Conn, Lisa M. Avery

Journal of Pharmacy Practice, October 23, 2019

 

The primary objective is to evaluate the relationship between antibiotic duration and all-cause 30-day readmission rates. Secondary outcomes include pneumonia-specific 30-day readmission rate and identification of risk factors for readmission.

Patients aged ≥18 years with a primary diagnosis of pneumonia from January 1, 2016, to December 31, 2016, were included in this single-center, retrospective cohort study. Patients were categorized by antibiotic therapy duration of ≤7 days (n = 139) or >7 days (n = 286), and outcomes were analyzed in both bivariate and multivariate models. A multivariate logistic regression was used to assess the relationship between all-cause 30-day readmission and antibiotic days.

Continue reading
49 Hits
0 Comments

WHO Practical toolkit: Antimicrobial Stewardship Programmes in Health-Care Facilities in Low- and Middle-Income Countries.

Following two years of hard work, involving international AMS experts, wide consultations and feasibility studies in LMICs, WHO is  happy to share the newly published “WHO Practical Toolkit: Antimicrobial Stewardship Programmes in Health-Care Facilities in Low- and Middle-Income Countries” view full toolkit here.

102 Hits
0 Comments

The Association of Antibiotic Stewardship With Fluoroquinolone Prescribing in Michigan Hospitals: A Multi-hospital Cohort Study

By Valerie M Vaughn, Tejal Gandhi, Anna Conlon, Vineet Chopra, Anurag N Malani, Scott A Flanders. Published in Clinical Infectious Diseases. To be published October 15, 2019.   

 

Fluoroquinolones increase the risk of Clostridioides difficile infection and antibiotic resistance. Hospitals often use pre-prescription approval or prospective audit and feedback to target fluoroquinolone prescribing. Whether these strategies impact aggregate fluoroquinolone use is unknown. This study is a 48-hospital, retrospective cohort of general-care, medical patients hospitalized with pneumonia or positive urine culture between December 2015–September 2017. Hospitals were surveyed on their use of pre-prescription approval and/or prospective audit and feedback to target fluoroquinolone prescribing during hospitalization (fluoroquinolone stewardship). After controlling for hospital clustering and patient factors, aggregate (inpatient and post-discharge) fluoroquinolone (ciprofloxacin, levofloxacin, moxifloxacin) exposure was compared between hospitals with and without fluoroquinolone stewardship. There were 11 748 patients (6820 pneumonia; 4928 positive urine culture) included at 48 hospitals. All hospitals responded to the survey: 29.2% (14/48) reported using pre-prescription approval and/or prospective audit and feedback to target fluoroquinolone prescribing. After adjustment, fluoroquinolone stewardship was associated with fewer patients receiving a fluoroquinolone (37.1% vs 48.2%; P = .01) and fewer fluoroquinolone treatment days per 1000 patients (2282 vs 3096 days/1000 patients; P = .01), driven by lower inpatient prescribing. However, most (66.6%) fluoroquinolone treatment days occurred after discharge, and hospitals with fluoroquinolone stewardship had twice as many new fluoroquinolone starts after discharge as hospitals without (15.6% vs 8.4%; P = .003). Hospital-based stewardship interventions targeting fluoroquinolone prescribing were associated with less fluoroquinolone prescribing during hospitalization, but not at discharge. To limit aggregate fluoroquinolone exposure, stewardship programs should target both inpatient and discharge prescribing.

Access article here.

109 Hits
0 Comments

Mycoplasma pneumoniae Carriage With De Novo Macrolide-Resistance and Breakthrough Pneumonia.

By Ammar Saadoon Alishlash, Thomas Prescott Atkinson, Charles Schlappi, Sixto M. Leal Jr, Ken B. Waites, Li Xiao. Published in Pediatrics. Published October 1, 2019.  

 

Mycoplasma pneumoniae pneumonia is prevalent in children and can be followed by upper airway carriage for months. Treatment of M pneumoniae pneumonia with macrolides is widespread and can lead to the development of macrolide resistance. The clinical consequences of chronic M pneumoniae carriage are unknown. In this article, we describe a child with acute lymphoblastic leukemia who developed macrolide-susceptible M pneumoniae pneumonia confirmed by nasopharyngeal secretions polymerase chain reaction and culture with good response to azithromycin. Five months later, the patient developed another M pneumoniae pneumonia that was diagnosed with positive macrolide-resistant M pneumoniae polymerase chain reaction and culture from the bronchoalveolar lavage. The child responded well to fluoroquinolones and eventually was discharged from the hospital. The M pneumoniae recovered from the second pneumonia is a novel strain and is genetically identical to the M pneumoniae that caused the first pneumonia, apart from the macrolide-resistance 23S ribosomal RNA gene. Both isolates are identical in both P1 (subtype 2 with a novel variant, 2bv) and multiple-locus variable number tandem repeat analysis type (53662). This is indicative of chronic M pneumoniae carriage with de novo macrolide-resistance mutation and subsequent breakthrough pneumonia that is reported for the first time here. Children with immunosuppression may be at increased risk of life-threatening macrolide-resistant pneumonia after M pneumoniae carriage. Further studies are required to evaluate the impact of this phenomenon. This will then guide strategies to limit the associated morbidity, such as testing for macrolide resistance, treatment of M pneumoniae pneumonia in high-risk children with bactericidal antibiotics (such as fluoroquinolones), and possibly eradication protocols of M pneumoniae carriage to prevent subsequent life-threatening infections.

Access article here.

116 Hits
0 Comments

Oral Lefamulin vs Moxifloxacin for Early Clinical Response Among Adults With Community-Acquired Bacterial Pneumonia

By Elizabeth Alexander, Lisa Goldberg, Anita F. Das, Gregory J. Moran, Christian Sandrock, Leanne B. Gasink, Patricia Spera, Carolyn Sweeney, Susanne Paukner, Wolfgang W. Wicha, Steven P. Gelone, Jennifer Schranz. JAMA. September 27, 2019.

 

Is 5-day oral lefamulin noninferior to 7-day oral moxifloxacin in the management of community-acquired bacterial pneumonia? In this randomized clinical trial that included 738 patients, the early clinical response at 96 hours (within a 24-hour window) after the first dose of study drug was 90.8% in the lefamulin group and 90.8% in the moxifloxacin group, a difference that met the noninferiority margin of 10%. This study demonstrated the noninferiority of oral lefamulin to oral moxifloxacin for the treatment of community-acquired bacterial pneumonia.

Access article here.

View the accompanying editorial ‘Lefamulin—A New Antibiotic for Community-Acquired Pneumonia’ by Preeti N. Malani.

Continue reading
104 Hits
0 Comments

Passage Adaptation Correlates With the Reduced Efficacy of the Influenza Vaccine

By Hui Chen, Jacob Josiah Santiago Alvarez, Sock Hoon Ng, Rasmus Nielsen, Weiwei Zhai

Clinical Infectious Diseases. October 1, 2019.

 

As a dominant seasonal influenza virus, H3N2 virus rapidly evolves in humans and is a constant threat to public health. Despite sustained research efforts, the efficacy of H3N2 vaccine has decreased rapidly. Even though antigenic drift and passage adaptation (substitutions accumulated during vaccine production in embryonated eggs) have been implicated in reduced vaccine efficacy (VE), their respective contributions to the phenomenon remain controversial.

We utilized mutational mapping, a powerful probabilistic method for studying sequence evolution, to analyze patterns of substitutions in different passage conditions for an unprecedented amount of H3N2 hemagglutinin sequences (n = 32 278).

Continue reading
92 Hits
0 Comments

Seven Versus 14 Days of Antibiotic Therapy for Uncomplicated Gram-negative Bacteremia: A Noninferiority Randomized Controlled Trial

By Dafna Yahav, Erica Franceschini, Fidi Koppel, Adi Turjeman, Tanya Babich, Roni Bitterman, Ami Neuberger, Nesrin Ghanem-Zoubi, Antonella Santoro, Noa Eliakim-Raz, Barak Pertzov, Tali Steinmetz, Anat Stern, Yaakov Dickstein, Elias Maroun, Hiba Zayyad, Jihad Bishara, Danny Alon, Yonatan Edel, Elad Goldberg, Claudia Venturelli, Cristina Mussini, Leonard Leibovici, Mical Paul, Bacteremia Duration Study Group

Clinical Infectious Diseases. October 1, 2019.

 

Gram-negative bacteremia is a major cause of morbidity and mortality in hospitalized patients. Data to guide the duration of antibiotic therapy are limited.

This was a randomized, multicenter, open-label, noninferiority trial. Inpatients with gram-negative bacteremia, who were afebrile and hemodynamically stable for at least 48 hours, were randomized to receive 7 days (intervention) or 14 days (control) of covering antibiotic therapy. Patients with uncontrolled focus of infection were excluded. The primary outcome at 90 days was a composite of all-cause mortality; relapse, suppurative, or distant complications; and readmission or extended hospitalization (>14 days). The noninferiority margin was set at 10%.

Continue reading
151 Hits
0 Comments

Co-trimoxazole or multivitamin multimineral supplement for post-discharge outcomes after severe anaemia in African children: a randomised controlled trial

By Kathryn Maitland, Peter Olupot-Olupot, Sarah Kiguli, George Chagaluka, Florence Alaroker, Robert O Opoka, Ayub Mpoya, Kevin Walsh, Charles Engoru, Julius Nteziyaremye, Machpherson Mallewa, Neil Kennedy, Margaret Nakuya, Cate Namayanja, Julianne Kayaga, Eva Nabawanuka, Tonny Sennyondo, Denis Aromut, Felistas Kumwenda, Cynthia Williams Musika, Margaret J Thomason, Imelda Bates, Michael Boele von Hensbroek, Jennifer A Evans, Sophie Uyoga, Prof Thomas N Williams, Gary Frost, Elizabeth C George, Diana M Gibb, A Sarah Walker, for theTRACT trial group

The Lancet Global Health. October 1, 2019

 

Severe anaemia is a leading cause of paediatric admission to hospital in Africa; post-discharge outcomes remain poor, with high 6-month mortality (8%) and re-admission (17%). We aimed to investigate post-discharge interventions that might improve outcomes.

Within the two-stratum, open-label, multicentre, factorial randomised TRACT trial, children aged 2 months to 12 years with severe anaemia, defined as haemoglobin of less than 6 g/dL, at admission to hospital (three in Uganda, one in Malawi) were randomly assigned, using sequentially numbered envelopes linked to a second non-sequentially numbered set of allocations stratified by centre and severity, to enhanced nutritional supplementation with iron and folate-containing multivitamin multimineral supplements versus iron and folate alone at treatment doses (usual care), and to co-trimoxazole versus no co-trimoxazole. All interventions were administered orally and were given for 3 months after discharge from hospital. Separately reported randomisations investigated transfusion management. The primary outcome was 180-day mortality. All analyses were done in the intention-to-treat population; follow-up was 180 days. This trial is registered with the International Standard Randomised Controlled Trial registry, ISRCTN84086586, and follow-up is complete.

Continue reading
153 Hits
0 Comments

Impact of Antibiotic Resistance on Treatment of Pneumococcal Disease in Ethiopia: An Agent-Based Modeling Simulation.

By Hui-Han Chen, Andy Stringer, Tadesse Eguale, Gauri G. Rao and Sachiko Ozawa. Published in The American Journal of Tropical Medicine and Hygiene. Published September 16, 2019.  

 

Antimicrobial resistance (AMR) is a growing threat to global health. Although AMR endangers continued effectiveness of antibiotics, the impact of AMR has been poorly estimated in low-income countries. This study sought to quantify the effect of AMR on treatments for pediatric pneumococcal disease in Ethiopia. We developed the DREAMR (Dynamic Representation of the Economics of AMR) model that simulated children younger than 5 years who acquire pneumococcal disease (pneumonia, meningitis, and acute otitis media) and seek treatment from various health facilities in Ethiopia over a year. We examined the AMR levels of three antibiotics (penicillin, amoxicillin, and ceftriaxone), treatment failures, and attributable deaths. We used a cost-of-illness method to assess the resulting economic impact of AMR from a societal perspective by estimating the direct and indirect treatment costs and productivity losses. Findings showed that AMR against antibiotics that were used to treat pneumococcal disease led to 195,763 treatment failures, which contributed to 2,925 child deaths annually in Ethiopia. Antimicrobial resistance resulted in a first-line treatment failure rate of 29.4%. In 1 year, the proportion of nonsusceptible Streptococcus pneumoniae bacteria increased by 2.1% and 0.5% for amoxicillin and penicillin and reduced by 0.3% for less commonly used ceftriaxone. Annual costs of AMR to treat pneumococcal disease were around US$15.8 million, including US$3.3 million for ineffective first-line treatments, US$3.7 million for second-line treatments, and US$8.9 million for long-term productivity losses. Antibiotic stewardship to reduce misuse and overuse of antibiotics is essential to maintain the effectiveness of antibiotics and lessen the health and economic burden of AMR.

Access article here.

79 Hits
0 Comments

Predictors of time to cough resolution in children with chronic wet cough treated with antibiotics after bronchoscopy.

By Oi Yin Wong, Julie M. Marchant, Stephanie T. Yerkovich, Anne B. Chang. Published in Pediatric Pulmonology. Published September 9, 2019.  

 

Chronic wet cough is common in pediatric pulmonology practice and is clinically important. Guidelines recommend treatment with antibiotics as their effectiveness has been proven. However, factors associated with duration of cough in response to antibiotics in children with chronic wet cough have not been prospectively examined. To determine if demographic, clinical and/or bronchoalveolar lavage (BAL) factors are associated with “time to cough resolution” in children with chronic wet cough treated with antibiotics after bronchoscopy. Data from children with chronic wet cough treated with antibiotics after bronchoscopy were extracted from a prospective cohort study database. Cough dairies were used to determine when the cough resolved. Associations between various factors with “time to cough resolution” were examined using regression. The median age of the 133 children was 2.4 years (interquartile range, 1.4‐4.9). Duration of prior cough at bronchoscopy was significantly positively related with “time to cough resolution” (β = .010; 95% confidence interval, 0.004‐0.017; P = .002). This translated to; for each month of prior cough, it took an extra 1.02 days to achieve cough resolution while on antibiotic treatment. Gender, age, diagnosis, tobacco smoke exposure, pneumonia history, blood cellularity, and BAL cellular and microbiology profiles were not significantly associated with time to cough resolution. In children with chronic wet cough, duration of cough before antibiotic treatment is a small but significant determinant of “time to cough resolution.” Research using standardized antibiotic regimes is required to provide clinical and/or biomarkers that can further identify factors associated with the response of chronic cough to antibiotic treatment.

Access article here.

74 Hits
0 Comments

Analysis of serious adverse events in a paediatric fast breathing pneumonia clinical trial in Malawi.

By Evangelyn Nkwopara, Robert Schmicker, Tisungane Mvalo, Melda Phiri, Ajib Phiri, Mari Couasnon, Eric D. McCollum, and Amy Sarah Ginsburg. Published in BMJ Open Respiratory Research. Published September 3, 2019.  

 

Pneumonia is the leading infectious killer of children. We conducted a double-blind, randomised controlled non-inferiority trial comparing placebo to amoxicillin treatment for fast breathing pneumonia in HIV-negative children aged 2–59 months in Malawi. Occurrence of serious adverse events (SAEs) during the trial were examined to assess disease progression, co-morbidities, recurrence of pneumonia and side effects of amoxicillin. Enrolled children with fast breathing for age and a history of cough <14 days or difficult breathing were randomised to either placebo or amoxicillin for 3 days, and followed for 14 days to track clinical characteristics and outcomes. Medical history, physical exam, laboratory results and any chest radiographs collected at screening, enrolment and during hospitalisation were evaluated. All SAE reports were reviewed for additional information regarding hospitalisation, course of treatment and outcome. In total, 102/1126 (9.0%) enrolled children with fast breathing pneumonia were reported to have a SAE. Seventy-five per cent (n=77) of SAEs were pneumonia-related (p<0.01). Children<2 years of age represented the greatest proportion (61/77, 79.2%) of those with a pneumonia-related SAE. In the amoxicillin group, there were 46 SAEs and 5 (10.9%) cases were identified as possibly related to study drug (4 gastroenteritis and 1 fever). There were no life-threatening pneumonia SAEs or deaths in either group, and by the time of exit from the study, all children recovered without sequelae. In this fast breathing pneumonia clinical trial, SAEs occurred infrequently in both the amoxicillin and placebo groups, and amoxicillin was well tolerated.

Access article here.

98 Hits
0 Comments

Antibiotic Resistance Profiles of Haemophilus influenzae Isolates from Children in 2016: A Multicenter Study in China.

By Hong-Jiao Wang, Chuan-Qing Wang, Chun-Zhen Hua, Hui Yu, Ting Zhang, Hong Zhang, Shi-Fu Wang, Ai-Wei Lin, Qing Cao, Wei-Chun Huang, Hui-Ling Deng, Shan-Cheng Cao, and Xue-jun Chen. Published in The Canadian Journal of Infectious Diseases and Medical Microbiology. Published August 14, 2019.

 

Haemophilus influenzae (HI) is a common cause of community-acquired pneumonia in children. In many countries, HI strains are increasingly resistant to ampicillin and other commonly prescribed antibiotics, posing a challenge for effective clinical treatment. This study was undertaken to determine the antibiotic resistance profiles of HI isolates from Chinese children and to provide guidelines for clinical treatment. Our Infectious Disease Surveillance of Pediatrics (ISPED) collaboration group includes six children's hospitals in different regions of China. The same protocols and guidelines were used by all collaborators for the culture and identification of HI. The Kirby–Bauer method was used to test antibiotic susceptibility, and a cefinase disc was used to detect β-lactamase activity. We isolated 2073 HI strains in 2016: 83.9% from the respiratory tract, 11.1% from vaginal secretions, and 0.5% from blood. Patients with respiratory isolates were significantly younger than nonrespiratory patients (P < 0.001). Of all 2073 strains, 50.3% were positive for β-lactamase and 58.1% were resistant to ampicillin; 9.3% were β-lactamase-negative and ampicillin-resistant. The resistance rates of the HI isolates to trimethoprim-sulfamethoxazole, azithromycin, cefuroxime, ampicillin-sulbactam, cefotaxime, and meropenem were 71.1%, 32.0%, 31.2%, 17.6%, 5.9%, and 0.2%, respectively. More than half of the HI strains isolated from Chinese children were resistant to ampicillin, primarily due to the production of β-lactamase. Cefotaxime and other third-generation cephalosporins could be the first choice for the treatment of ampicillin-resistant HI infections.\

Access article here.

76 Hits
0 Comments

Excess Antibiotic Treatment Duration and Adverse Events in Patients Hospitalized With Pneumonia: A Multihospital Cohort Study

By Valerie M. Vaughn, Scott A. Flanders, Ashley Snyder, Anna Conlon, Mary A.M. Rogers, Anurag N. Malani, Elizabeth McLaughlin, Sarah Bloemers, Arjun Srinivasan, Jerod Nagel, Scott Kaatz, Danielle Osterholzer, Rama Thyagarajan, Lama Hsaiky, Vineet Chopra, Tejal N. Gandhi

Annals of Internal Medicine, August 6, 2019

 

Randomized trials demonstrate no benefit from antibiotic treatment exceeding the shortest effective duration.The primary outcome was the rate of excess antibiotic treatment duration (excess days per 30-day period). Excess days were calculated by subtracting each patient's shortest effective (expected) treatment duration (based on time to clinical stability, pathogen, and pneumonia classification [community-acquired vs. health care–associated]) from the actual duration. Negative binomial generalized estimating equations (GEEs) were used to calculate rate ratios to assess predictors of 30-day rates of excess duration. Patient outcomes, assessed at 30 days via the medical record and telephone calls, were evaluated using logit GEEs that adjusted for patient characteristics and probability of treatment.

Two thirds (67.8% [4391 of 6481]) of patients received excess antibiotic therapy. Antibiotics prescribed at discharge accounted for 93.2% of excess duration. Patients who had respiratory cultures or nonculture diagnostic testing, had a longer stay, received a high-risk antibiotic in the prior 90 days, had community-acquired pneumonia, or did not have a total antibiotic treatment duration documented at discharge were more likely to receive excess treatment. Excess treatment was not associated with lower rates of any adverse outcomes, including death, readmission, emergency department visit, or Clostridioides difficile infection. Each excess day of treatment was associated with a 5% increase in the odds of antibiotic-associated adverse events reported by patients after discharge.

Continue reading
130 Hits
0 Comments

Early Clinical Response in Community-acquired Bacterial Pneumonia: From Clinical Endpoint to Clinical Practice

By Julio A Ramirez,  Evan Tzanis,  Marla Curran,  Robert Noble,  Surya Chitra,  Amy Manley, Courtney Kirsch,  Paul C McGovern

Clinical Infectious Diseases, August 1, 2019

 

Early clinical response (ECR) is a new endpoint to determine whether a drug should be approved for community-acquired bacterial pneumonia in the United States. The Omadacycline for Pneumonia Treatment In the Community (OPTIC) phase III study demonstrated noninferiority of omadacycline to moxifloxacin using this endpoint. This study describes the performance of the ECR endpoint and clinical stability relative to a posttreatment evaluation (PTE) of clinical success.

ECR was defined as symptom improvement 72–120 hours after the first dose of study drug (ECR window), no use of rescue antibiotics, and patient survival. Clinical success at PTE was an investigator assessment of success. Clinical stability was defined based on vital sign stabilization, described in the American Thoracic Society and Infectious Diseases Society of America community-acquired pneumonia treatment guidelines.

Continue reading
110 Hits
0 Comments

Risk Factors for Unnecessary Antibiotic Therapy: A Major Role for Clinical Management

By Pierre-Marie Roger,  Eve Montera,  Diane Lesselingue,  Nathalie Troadec,  Patrick Charlot, Agnès Simand,  Agnès Rancezot,  Olivier Pantaloni,  Thomas Guichard, Véronique Dautezac,  Cécile Landais,  Frédéric Assi,  Thierry Levent,  Collaborators

Clinical Infectious Diseases, To be Published August 1, 2019

 

Assessment of antimicrobial use places an emphasis on therapeutic aspects of infected patients. Our aim was to determine the risk factors for unnecessary antibiotic therapy (UAT).

This was a prospective, multicenter study evaluating all curative antibiotic therapies prescribed over 2 consecutive days through the same electronic medical records. Each item that could participate in these prescriptions was collected from the computerized file (reason for hospitalization, comorbid conditions, suspected or definitive diagnosis of infection, microbial analyses). UAT was defined as the recognition of noninfectious sydromes (NIS), nonbacterial infections, use of redundant antimicrobials, and continuation of empirical broad-spectrum antimicrobials.

Continue reading
150 Hits
0 Comments

Comparison of 3 Days Amoxicillin Versus 5 Days Co-Trimoxazole for Treatment of Fast-breathing Pneumonia by Community Health Workers in Children Aged 2–59 Months in Pakistan: A Cluster-randomized Trial

By Salim Sadruddin,  Ibad ul Haque Khan,  Matthew P Fox,  Abdul Bari,  Attaullah Khan, Donald M Thea,  Amanullah Khan,  Inamullah Khan,  Ijaz Ahmad,  Shamim A Qazi

Clinical Infectious Diseases, To be Published August 1, 2019

 

Globally, most deaths due to childhood pneumonia occur at the community level. Some countries are still using oral co-trimoxazole, despite a World Health Organization recommendation of oral amoxicillin for the treatment of fast-breathing pneumonia in children at the community level.

We conducted an unblinded, cluster-randomized, controlled-equivalency trial in Haripur District, Pakistan. Children 2–59 months of age with fast-breathing pneumonia were treated with oral amoxicillin suspension (50 mg/kg/day) for 3 days in 14 intervention clusters and oral co-trimoxazole suspension (8 mg trimethoprim/kg and 40 mg sulfamethoxazole/kg/day) for 5 days in 14 control clusters by lady health workers (LHW). The primary outcome was treatment failure by day 4 for intervention clusters and by day 6 for control clusters. The analysis was per protocol.

Continue reading
104 Hits
0 Comments