Posts filed under ‘Meta-Análisis’

Intravenous fosfomycin-back to the future. Systematic review and meta-analysis of the clinical literature.

Clin Microbiol Infect. 2016 Dec 9. pii: S1198-743X(16)30610-3

Grabein B1, Graninger W2, Rodríguez Baño J3, Dinh A4, Liesenfeld DB5.

Author information

1 Department of Clinical Microbiology and Hospital Hygiene, Munich University Hospital, Munich, Germany.

2 Institute for Infectiology, Karl Landsteiner Society, Vienna, Austria.

3 Unidad Clínica de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospital Universitarios Virgen Macarena y Virgen del Rocío, Departamento de Medicina, Universidad de Sevilla-IBIS, Sevilla, Spain; Spanish Network for Research in Infectious Diseases, Instituto de Salud Carlos III, Madrid, Spain.

4 Infectious Disease Unit, R. Poincaré University Hospital, Garches, AP-HP, Versailles Saint Quentin University, Garches, France.

5 InfectoPharm Arzneimittel und Consilium GmbH, Heppenheim, Germany. Electronic address:



We conducted a systematic review and meta-analysis to summarize the clinical evidence and usage patterns of intravenous fosfomycin from its development to the present time.


PubMed, the Cochrane Library and local journals were searched for relevant studies reporting aggregated data of intravenous fosfomycin use in adults and children, with no restrictions regarding study design. Single case reports were excluded. Data were systematically abstracted for all included studies. Clinical and microbiological efficacy from randomized controlled and comparative observational studies were synthesized using meta-analysis to calculate pooled effect sizes.


In all, 128 studies on intravenous fosfomycin in 5527 patients were evaluated. Fosfomycin was predominantly used for sepsis/bacteraemia, urinary tract, respiratory tract, bone and joint, and central nervous system infections. No difference in clinical (OR 1.44, 95% CI 0.96-2.15) or microbiological (OR 1.28, 95% CI 0.82-2.01) efficacy between fosfomycin and other antibiotics was observed in comparative trials. The pooled estimate for resistance development during fosfomycin monotherapy was 3.4% (95% CI 1.8%-5.1%). Fosfomycin showed a favourable safety profile, with generally mild adverse events not requiring discontinuation of treatment. Included studies explored intravenous fosfomycin as an anti-staphylococcal agent in monotherapy and combination therapy, whereas studies from 1990 focused on combination therapy (fosfoymcin + β-lactams or aminoglycosides) for challenging infections frequently caused by multidrug-resistant organisms.


Intravenous fosfomycin can play a vital role in the antibiotic armamentarium, given its long history of effective and safe use. However, well-designed randomized controlled trials are still desired.


May 7, 2017 at 2:55 pm

Impact of Outpatient Neuraminidase Inhibitor Treatment in Patients Infected With Influenza A(H1N1)pdm09 at High Risk of Hospitalization: An Individual Participant Data Metaanalysis

Clin Inf Dis May 15, 2017 V.64 N.10

Sudhir Venkatesan; Puja R. Myles; Jo Leonardi-Bee; Stella G. Muthuri; Malak Al Masri …

Our findings suggest that in populations at high risk for hospital admission, patients with laboratory-confirmed or clinically diagnosed A(H1N1)pdm09 infection, NAI treatment in the community or outpatient settings is associated with reduced likelihood of subsequent hospital admission.


May 6, 2017 at 3:56 pm

Long-term outcomes of infective encephalitis in children: a systematic review and meta-analysis.

Dev Med Child Neurol. 2016 Nov;58(11):1108-1115.

 doi: 10.1111/dmcn.13197. Epub 2016 Jul 16.

Khandaker G1,2,3, Jung J4, Britton PN4,5,6, King C7, Yin JK7,8, Jones CA4,5,6.

Author information

1Discipline of Child and Adolescent Health, Sydney Medical School, University of Sydney, Sydney, NSW, Australia.

2National Centre for Immunisation Research and Surveillance, The Children’s Hospital at Westmead, Sydney, NSW, Australia.

3Marie Bashir Institute for Infectious Diseases and Biosecurity Institute (MBI), University of Sydney, Sydney, NSW, Australia.

4Discipline of Child and Adolescent Health, Sydney Medical School, University of Sydney, Sydney, NSW, Australia.

5Marie Bashir Institute for Infectious Diseases and Biosecurity Institute (MBI), University of Sydney, Sydney, NSW, Australia.

6Department of Infectious Diseases and Microbiology, The Children’s Hospital at Westmead, Sydney, NSW, Australia.

7National Centre for Immunisation Research and Surveillance, The Children’s Hospital at Westmead, Sydney, NSW, Australia.

8Sydney School of Public Health, University of Sydney, Sydney, NSW, Australia.



The long-term outcomes of childhood infective encephalitis are variable and not well quantified. We aimed to systematically review the literature and undertake meta-analyses on predetermined outcomes to address this knowledge gap and identify areas for future research.


We searched electronic databases, performed complementary reviews of references of fully extracted articles, and made contact with experts on infective encephalitis. Articles published up until April 2016 were selected for screening.


We evaluated sequelae of 1018 survivors of childhood infective encephalitis (934 with complete follow-up) from 16 studies. Mean age during acute encephalitis episodes was 5 years 3.6 months (range 1.2mo-17y), 57.6% were male (500/868), and mean follow-up period was 4 years 1.2 months (range 1-12y). Incomplete recovery was reported in 312 children (42.0%; 95% confidence interval [CI] 31.6-53.1% in pooled estimate). Among the other sequelae, developmental delay, abnormal behaviour, motor impairment, and seizures were reported among 35.0% (95% CI 10.0-65.0%), 18.0% (95% CI 8.0-31.0%), 17.0% (95% CI 10.0-26.0%), and 10.0% (95% CI 6.0-14.0%) respectively.


Almost half of childhood infective encephalitis survivors report incomplete recovery in the long-term; most commonly developmental delay, behavioural abnormality, and neurological impairments (i.e. seizure). Well designed, large-scale prospective studies are needed to better quantify neurodevelopmental sequelae among childhood encephalitis survivors.


February 24, 2017 at 12:22 pm

Safety, tolerability, and efficacy of repeated doses of dihydroartemisinin-piperaquine for prevention and treatment of malaria: a systematic review and meta-analysis

Lancet Infectious Diseases February 2017 V.17 N.2 P.184–193

Julie Gutman, MD,  Stephanie Kovacs, PhD, Prof Grant Dorsey, MD, Prof Andy Stergachis, PhD, Prof Feiko O ter Kuile, MD


Intermittent preventive treatment (IPT) for malaria is used in infants, children, adults, and pregnant women. Dihydroartemisinin-piperaquine (DP) is an effective, well tolerated artemisinin-based combination therapy. The long half-life of piperaquine makes it attractive for IPT. We conducted a systematic review and meta-analysis to establish the efficacy and safety of repeated treatment with DP.


Following PRISMA guidelines, we searched multiple databases on Sept 1, 2016, with the terms: “human” AND “dihydroartemisinin-piperaquine” OR “DHA-PPQ”. Studies were eligible if they were randomised controlled trials (RCTs) or prospective cohort studies involving repeat exposures to standard 3-day courses of DP for either seasonal malaria chemoprevention, mass drug administration, or treatment of clinical malaria, conducted at any time and in any geographic location. Random-effects meta-analysis was used to generate pooled incidence rate ratios and relative risks, or risk differences.


11 studies were included: two repeat treatment studies (one in children younger than 5 years and one in pregnant women), and nine IPT trials (five in children younger than 5 years, one in schoolchildren, one in adults, two in pregnant women). Comparator interventions included placebo, artemether-lumefantrine, sulfadoxine-pyrimethamine (SP), SP+amodiaquine, SP+piperaquine, SP+chloroquine, and co-trimoxazole. Of 14 628 participants, 3935 received multiple DP courses (2–18). Monthly IPT-DP was associated with an 84% reduction in the incidence of malaria parasitaemia measured by microscopy compared with placebo. Monthly IPT-DP was associated with fewer serious adverse events than placebo, daily co-trimoxazole, or monthly SP. Among 56 IPT-DP recipients (26 children, 30 pregnant women) with cardiac parameters, all QTc intervals were within normal limits, with no significant increase in QTc prolongation with increasing courses of DP.


Monthly DP appears well tolerated and effective for IPT. Additional data are needed in pregnancy and to further explore the cardiac safety with monthly dosing.


Bill & Melinda Gates Foundation and NIH.



February 1, 2017 at 2:09 pm

Is β-Lactam Plus Macrolide More Effective than β-Lactam Plus Fluoroquinolone among Patients with Severe Community-Acquired Pneumonia?: a Systemic Review and Meta-Analysis.

J Korean Med Sci. 2017 Jan;32(1):77-84. doi: 10.3346/jkms.2017.32.1.77.

Lee JH1, Kim HJ2, Kim YH3.

Author information

1Department of Internal Medicine, Jeju National University Hospital, Jeju, Korea.

2Institute for Evidence-based Medicine, Department of Preventive Medicine, Korea University College of Medicine, Seoul, Korea.

3Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kyung Hee University Hospital at Gangdong, Seoul, Korea.


Adding either macrolide or fluoroquinolone (FQ) to β-lactam has been recommended for patients with severe community-acquired pneumonia (CAP).

However, due to the limited evidence available, there is a question as to the superiority of the two combination therapies. The MEDLINE, EMBASE, Cochrane Central Register, Scopus, and Web of Science databases were searched for systematic review and meta-analysis.

A total of eight trials were analyzed. The total number of patients in the β-lactam plus macrolide (BL-M) and β-lactam plus fluoroquinolone (BL-F) groups was 2,273 and 1,600, respectively. Overall mortality of the BL-M group was lower than that of the BL-F group (19.4% vs. 26.8%), which showed statistical significance (odds ratio [OR], 0.68; 95% confidence interval [CI], 0.49 to 0.94; P = 0.02). Length of hospital stay was reduced in the BL-M group compared to the BL-F group (mean difference, -3.05 days; 95% CI, -6.01 to -0.09; P = 0.04).

However, there was no significant difference in length of intensive care unit (ICU) stay between the two groups.

Among patients with severe CAP, BL-M therapy may better reduce overall mortality and length of hospital stay than BL-F therapy.

However, we could not elicit strong conclusions from the available trials due to high risk of bias and methodological limitations.


January 15, 2017 at 3:46 pm

Prognostic implications of aspiration pneumonia in patients with community acquired pneumonia: A systematic review with meta-analysis.

Sci Rep. 2016 Dec 7;6:38097.

Komiya K1,2,3, Rubin BK1, Kadota JI2, Mukae H4, Akaba T1, Moro H5, Aoki N5, Tsukada H6, Noguchi S7, Shime N8, Takahashi O9, Kohno S4.

Author information

1Department of Pediatrics, Virginia Commonwealth University School of Medicine, 1217 East Marshall Street: KMSB, Room 215 Richmond, Virginia 23298, USA.

2Respiratory Medicine and Infectious Diseases, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Yufu, Oita, 879-5593, Japan.

3Clinical Research Center of Respiratory Medicine, Tenshindo Hetsugi Hospital, 5956 Nihongi, Nakahetsugi, Oita, 879-7761, Japan.

4Second Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.

5Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences, 757 Asahi-machi, Chuo-ku, Niigata, 951-8510, Japan.

6Department of Respiratory Medicine/Infectious Disease, Niigata City General Hospital, 463-7 Shumoku, Chuo-ku, Niigata, 950-1197, Japan.

7Department of Respiratory Medicine, University of Occupational and Environmental Health, 1-1 Idaigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan.

8Department of Emergency and Critical Care Medicine, Institute of Biomedical &Health Sciences, Hiroshima University Advanced Emergency and Critical Care Center, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8553, Japan.

9Center for Clinical Epidemiology, St. Luke’s Life Science Institute, 10-1 Akashicho, Chuo-ku, Tokyo, 104-0044, Japan.


Aspiration pneumonia is thought to be associated with a poor outcome in patients with community acquired pneumonia (CAP). However, there has been no systematic review regarding the impact of aspiration pneumonia on the outcomes in patients with CAP.

This review was conducted using the MOOSE guidelines

Patients: patients defined CAP.


aspiration pneumonia defined as pneumonia in patients who have aspiration risk. Comparison: confirmed pneumonia in patients who were not considered to be at high risk for oral aspiration.


mortality, hospital readmission or recurrent pneumonia. Three investigators independently identified published cohort studies from PubMed, CENTRAL database, and EMBASE. Nineteen studies were included for this systematic review. Aspiration pneumonia increased in-hospital mortality (relative risk, 3.62; 95% CI, 2.65-4.96; P < 0.001, seven studies) and 30-day mortality (3.57; 2.18-5.86; P < 0.001, five studies). In contrast, aspiration pneumonia was associated with decreased ICU mortality (relative risk, 0.40; 95% CI, 0.26-0.60; P < 0.00001, four studies). Although there are insufficient data to perform a meta-analysis on long-term mortality, recurrent pneumonia, and hospital readmission, the few reported studies suggest that aspiration pneumonia is also associated with these poor outcomes. In conclusion, aspiration pneumonia was associated with both higher in-hospital and 30-day mortality in patients with CAP outside ICU settings.


January 15, 2017 at 3:44 pm

Efficacy of polymyxins in the treatment of carbapenem-resistant Enterobacteriaceae infections: a systematic review and meta-analysis.

Braz J Infect Dis. 2015 Mar-Apr;19(2):170-80.

Ni W1, Cai X1, Wei C1, Di X2, Cui J3, Wang R2, Liu Y1.

Author information

1Department of Respiratory Diseases, Chinese People’s Liberation Army General Hospital, Beijing, China.

2Department of Clinical Pharmacology, Chinese People’s Liberation Army General Hospital, Beijing, China.

3Department of Respiratory Diseases, Chinese People’s Liberation Army General Hospital, Beijing, China. Electronic address:


In recent years, carbapenem-resistant Enterobacteriaceae has become endemic in many countries. Because of limited treatment options, the abandoned “old antibiotics”, polymyxins, have been reintroduced to the clinic.

To evaluate the clinical efficacy of polymyxins in the treatment of infections caused by carbapenem-resistant Enterobacteriaceae, we systemically searched the PubMed, Embase, and Cochrane Library databases and analyzed the available evidence.

The Preferred Reporting Items for Systematic reviews and Meta-Analysis statement were followed, and the I(2) method was used for heterogeneity. Nineteen controlled and six single-arm cohort studies comprising 1086 patients met the inclusion criteria.

For controlled studies, no significant difference was noted for overall mortality (OR, 0.79; 95% CI, 0.58-1.08; p=0.15), clinical response rate (OR, 1.24; 95% CI, 0.61-2.54; p=0.55), or microbiological response rate (OR, 0.59; 95% CI, 0.26-1.36; p=0.22) between polymyxin-treated groups and the control groups.

Subgroup analyses showed that 28-day or 30-day mortality was lower in patients who received polymyxin combination therapy than in those who received monotherapy (OR, 0.36; 95% CI, 0.19-0.68; p<0.01) and the control groups (OR, 0.49; 95% CI, 0.31-0.75; p<0.01).

The results of the six single-arm studies were in accordance with the findings of controlled studies. One controlled and two single-arm studies that evaluated the occurrence of nephrotoxicity reported a pooled incidence rate of 19.2%.

Our results suggest that polymyxins may be as efficacious as other antimicrobial therapies for the treatment of carbapenem-resistant Enterobacteriaceae infection. Compared to polymyxin monotherapy, combination regimens may achieve lower 28-day or 30-day mortality.

Future large-volume, well-designed randomized control trials are required to determine the role of polymyxins in treating carbapenem-resistant Enterobacteriaceae infections.


December 30, 2016 at 7:52 am

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