SUMMARYThe treatment of bacterial infections suffers from two major problems: spread of multidrug-resistant (MDR) or extensively drug-resistant (XDR) pathogens and lack of development of new antibiotics active against such MDR and XDR bacteria. As a result, physicians have turned to older antibiotics, such as polymyxins, tetracyclines, and aminoglycosides. Lately, due to development of resistance to these agents, fosfomycin has gained attention, as it has remained active against both Gram-positive and Gram-negative MDR and XDR bacteria. New data of higher quality have become available, and several issues were clarified further. In this review, we summarize the available fosfomycin data regarding pharmacokinetic and pharmacodynamic properties, thein vitroactivity against susceptible and antibiotic-resistant bacteria, mechanisms of resistance and development of resistance during treatment, synergy and antagonism with other antibiotics, clinical effectiveness, and adverse events. Issues that need to be studied further are also discussed.

We aimed to assess the accuracy of measuring serum or plasma (1→3)-β-D-glucan (BDG) for the diagnosis of invasive fungal infections (IFIs) by means of a meta-analysis of relevant studies. We searched in bibliographic databases for relevant cohort or case-control studies. We primarily compared BDG between patients with proven or probable IFIs (excluding Pneumocystis jirovecii infections), according to the criteria of the European Organization for Research and Treatment of Cancer/Mycoses Study Group or similar criteria, and patients without IFIs (excluding healthy individuals as controls). A total of 2979 patients (594 with proven or probable IFIs), included in 16 studies, were analyzed. The pooled sensitivity of BDG was 76.8% (95% confidence interval [CI], 67.1%-84.3%), and the specificity was 85.3% (95% CI, 79.6%-89.7%). The area under the summary receiver operating characteristic curve was 0.89. Marked statistical heterogeneity was noted. BDG has good diagnostic accuracy for distinguishing proven or probable IFIs from no IFIs. It can be useful in clinical practice, if implemented in the proper setting and interpreted after consideration of its limitations.

Fosfomycin represents a potential last-resort treatment option for infections with certain multidrug-resistant (MDR) Gram-negative pathogens. We evaluated double-drug combinations of fosfomycin with imipenem, meropenem, doripenem, colistin, netilmicin, and tigecycline for in vitro synergy against 100 MDR Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa clinical isolates, using the Etest method. Synergy was defined as a fractional inhibitory concentration index ≤ 0.5. The isolates were consecutively collected at a university hospital in Greece from various clinical specimens. Against 50 serine carbapenemase-producing K. pneumoniae isolates, synergy of fosfomycin with imipenem, meropenem, doripenem, colistin, netilmicin, and tigecycline was observed for 74.0%, 70.0%, 74.0%, 36.0%, 42.0%, and 30.0% of the isolates, respectively. Against 14 extended-spectrum β-lactamase (ESBL)-producing K. pneumoniae isolates, synergy of fosfomycin with imipenem, meropenem, doripenem, colistin, netilmicin, and tigecycline was observed for 78.6%, 42.9%, 42.9%, 7.1%, 42.9%, and 21.4%, respectively; for 20 ESBL-producing E. coli isolates, the corresponding values were 55.0%, 25.0%, 30.0%, 15.0%, 25.0%, and 25.0%; and for 15 MDR P. aeruginosa isolates, the corresponding values were 46.7%, 53.3%, 73.3%, 13.3% , 13.3%, and 13.3%. Antagonism was not observed for any of the combinations tested. Further studies are needed in order to confirm the clinical relevance of the above findings.

Our findings suggest that serum PCT at presentation has very good diagnostic accuracy (AUC = 0.87) for the diagnosis of neonatal sepsis. However, in view of the marked observed statistical heterogeneity, along with the lack of a uniform definition for neonatal sepsis, the interpretation of these findings should be done with appropriate caution.

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