SUMMARY The spread of Enterobacteriaceae , primarily Klebsiella pneumoniae , producing KPC, VIM, IMP, and NDM carbapenemases, is causing an unprecedented public health crisis. Carbapenemase-producing enterobacteria (CPE) infect mainly hospitalized patients but also have been spreading in long-term care facilities. Given their multidrug resistance, therapeutic options are limited and, as discussed here, should be reevaluated and optimized. Based on susceptibility data, colistin and tigecycline are commonly used to treat CPE infections. Nevertheless, a review of the literature revealed high failure rates in cases of monotherapy with these drugs, whilst monotherapy with either a carbapenem or an aminoglycoside appeared to be more effective. Combination therapies not including carbapenems were comparable to aminoglycoside and carbapenem monotherapies. Higher success rates have been achieved with carbapenem-containing combinations. Pharmacodynamic simulations and experimental infections indicate that modification of the current patterns of carbapenem use against CPE warrants further attention. Epidemiological data, though fragmentary in many countries, indicate CPE foci and transmission routes, to some extent, whilst also underlining the lack of international collaborative systems that could react promptly and effectively. Fortunately, there are sound studies showing successful containment of CPE by bundles of measures, among which the most important are active surveillance cultures, separation of carriers, and assignment of dedicated nursing staff.

VIM-1-producing Klebsiella pneumoniae (VPKP) is an emerging pathogen. A prospective observational study was conducted to evaluate the importance of VIM production on outcome of patients with K. pneumoniae bloodstream infections (BSIs). Consecutive patients with K. pneumoniae BSIs were identified and followed up until patient discharge or death. A total of 162 patients were included in the analysis; 67 (41.4%) were infected with VPKP, and 95 were infected with non-VPKP. Fourteen of the patients infected with VPKP were carbapenem resistant (Carb r ) (MIC > 4 g/ml), whereas none of the non-VPKP exhibited carbapenem resistance. The patients infected with a Carb r organism were more likely (odds ratio, 4.08; 95% confidence interval [CI], 1.29 to 12.85; P ‫؍‬ 0.02) to receive inappropriate empirical therapy. The all-cause 14-day mortality rates were 15.8% (15 of 95) for patients infected with VIM-negative organisms, 18.9% (10 of 53) for those infected with VIM-positive carbapenem-susceptible organisms, and 42.9% (6 of 14) for those infected with VIM-positive Carb r organisms (P ‫؍‬ 0.044). In Cox regression analysis, age (hazard ratio [HR], 1.03; 95% CI, 1.01 to 1.06; P ‫؍‬ 0.021), rapidly fatal underlying disease (HR, 2.84; 95% CI, 1.26 to 6.39; P ‫؍‬ 0.012), and carbapenem resistance (HR, 2.83; 95% CI, 1.08 to 7.41; P ‫؍‬ 0.035) were independent predictors of death. After adjustment for inappropriate empirical or definitive therapy, the effect of carbapenem resistance on outcome was reduced to a level of nonsignificance. In patients with K. pneumoniae BSIs, carbapenem resistance, advanced, age, and severity of underlying disease were independent predictors of outcome, whereas VIM production had no effect on mortality. The higher mortality associated with carbapenem resistance was probably mediated by the failure to provide effective therapy.Over the last few years, the reliance on carbapenems has been challenged owing to the wide spread of acquired metallo-␤-lactamases [MBLs] (2,11,20,25,31). Two dominant groups of acquired MBLs have been recognized: the IMP and VIM types. This class of enzymes is characterized by the ability to hydrolyze carbapenems and all available ␤-lactams with the exception of aztreonam. Moreover, since the MBL genes are linked to other resistance determinants within the same integron or plasmid, MBL-producing organisms are commonly multidrug resistant, further compromising our therapeutic options (8,26,28).MBLs have spread throughout the world with an overall trend moving from Pseudomonas aeruginosa into Enterobacteriaceae (9,10,14,16,18,22,23,28). Recently, there have been several reports on the emergence of VIM-producing Klebsiella pneumoniae (VPKP), mainly in Southern Europe (16,20). In Greece, VPKP isolates are endemic in various hospitals and cause life-threatening infections (5,8,29). Based on previous reports (30) and on the National Surveillance System for Antibiotic Resistance Database (www.mednet.gr/whonet/top .htm), the dissemination of such isolates appears to have occurred in a r...

BackgroundDuring 2011, a dramatic increase (1600%) of reported HIV-1 infections among injecting drug users (IDUs) was noted in Athens, Greece. We herein assess the potential causal pathways associated with this outbreak.MethodsOur study employed high resolution HIV-1 phylogenetic and phylogeographic analyses. We examined also longitudinal data of ecological variables such as the annual growth of gross domestic product (GDP) of Greece in association with HIV-1 and HCV sentinel prevalence in IDUs, unemployment and homelessness rates and HIV transmission networks in Athens IDUs before and during economic recession (2008–2012).ResultsIDU isolates sampled in 2011 and 2012 suggested transmission networks in 94.6% and 92.7% of the cases in striking contrast with the sporadic networking (5%) during 1998–2009. The geographic origin of most HIV-1 isolates was consistent with the recently documented migratory waves in Greece. The decline in GDP was inversely correlated with annual prevalence rates of HIV and HCV and with unemployment and homelessness rates in IDUs (all p<0.001). The slope of anti-HCV prevalence in the sentinel populations of IDUs and in “new” drug injectors was found 120 and 1.9-fold (p = 0.007, p = 0.08 respectively) higher in 2008–2012 (economic recession) compared with 2002–2006. The median (25th, 75th) size of transmission networks were 34 (12, 58) and 2 (2, 2) (p = 0.057) in 2008–2012 and 1998–2007, respectively. The coverage of harm reduction services was low throughout the study period.ConclusionsScaling-up harm reduction services and addressing social and structural factors related to the current economic crisis should be urgently considered in environments where HIV-1 outbreaks may occur.

Seven immunocompetent patients aged > 50 years old presented with herpes zoster (HZ) infection in a median of 9 days (range 7–20) after vaccination against SARS-CoV-2. The occurrence of HZ within the time window 1–21 days after vaccination defined for increased risk and the reported T cell-mediated immunity involvement suggest that COVID-19 vaccination is a probable cause of HZ. These cases support the importance of continuing assessment of vaccine safety during the ongoing massive vaccination for the COVID-19 pandemic and encourage reporting and communication of any vaccination-associated adverse event.