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.

Carbapenemases in Klebsiella pneumoniae and Other Enterobacteriaceae: an Evolving Crisis of Global Dimensions

Over the past 10 years, dissemination of Klebsiella pneumoniae carbapenemase (KPC) has led to an increase in the prevalence of carbapenem-resistant Enterobacteriaceae (CRE) in the United States. Infections caused by CRE have limited treatment options and have been associated with high mortality rates. In the previous year, other carbapenemase subtypes, including New Delhi metallo-β-lactamase, have been identified among Enterobacteriaceae in the United States. Like KPC, these enzymes are frequently found on mobile genetic elements and have the potential to spread widely. As a result, preventing both CRE transmission and CRE infections have become important public health objectives. This review describes the current epidemiology of CRE in the United States and highlights important prevention strategies.

/pdf/carbapenem-resistant-enterobacteriaceae-epidemiology-and-596j8hp5nw.pdf

Carbapenem-Resistant Enterobacteriaceae: Epidemiology and Prevention

BACKGROUND In 2013, New York began requiring hospitals to follow protocols for the early identification and treatment of sepsis. However, there is controversy about whether more rapid treatment of sepsis improves outcomes in patients. METHODS We studied data from patients with sepsis and septic shock that were reported to the New York State Department of Health from April 1, 2014, to June 30, 2016. Patients had a sepsis protocol initiated within 6 hours after arrival in the emergency department and had all items in a 3‐hour bundle of care for patients with sepsis (i.e., blood cultures, broad‐spectrum antibiotic agents, and lactate measurement) completed within 12 hours. Multilevel models were used to assess the associations between the time until completion of the 3‐hour bundle and risk‐adjusted mortality. We also examined the times to the administration of antibiotics and to the completion of an initial bolus of intravenous fluid. RESULTS Among 49,331 patients at 149 hospitals, 40,696 (82.5%) had the 3‐hour bundle completed within 3 hours. The median time to completion of the 3‐hour bundle was 1.30 hours (interquartile range, 0.65 to 2.35), the median time to the administration of antibiotics was 0.95 hours (interquartile range, 0.35 to 1.95), and the median time to completion of the fluid bolus was 2.56 hours (interquartile range, 1.33 to 4.20). Among patients who had the 3‐hour bundle completed within 12 hours, a longer time to the completion of the bundle was associated with higher risk‐adjusted in‐hospital mortality (odds ratio, 1.04 per hour; 95% confidence interval [CI], 1.02 to 1.05; P<0.001), as was a longer time to the administration of antibiotics (odds ratio, 1.04 per hour; 95% CI, 1.03 to 1.06; P<0.001) but not a longer time to the completion of a bolus of intravenous fluids (odds ratio, 1.01 per hour; 95% CI, 0.99 to 1.02; P=0.21). CONCLUSIONS More rapid completion of a 3‐hour bundle of sepsis care and rapid administration of antibiotics, but not rapid completion of an initial bolus of intravenous fluids, were associated with lower risk‐adjusted in‐hospital mortality. (Funded by the National Institutes of Health and others.)

Supplement to: Time to treatment and mortality during mandated emergency care for sepsis.

https://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(14)60007-0/pdf

ESCMID guidelines for the management of the infection control measures to reduce transmission of multidrug-resistant Gram-negative bacteria in hospitalized patients

Fungal spores can account for large proportions of air particulate matter, and they may potentially influence the hydrological cycle and climate as nuclei for water droplets and ice crystals in clouds, fog, and precipitation. Moreover, some fungi are major pathogens and allergens. The diversity of airborne fungi is, however, not well-known. By DNA analysis we found pronounced differences in the relative abundance and seasonal cycles of various groups of fungi in coarse and fine particulate matter, with more plant pathogens in the coarse fraction and more human pathogens and allergens in the respirable fine particle fraction (<3 μm). Moreover, the ratio of Basidiomycota to Ascomycota was found to be much higher than previously assumed, which might also apply to the biosphere.

High Diversity of Fungi in Air Particulate Matter

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1469-0691.2012.03964.x

How to discriminate contamination from bloodstream infection due to coagulase-negative staphylococci: a prospective study with 654 patients.

Address reprint requests to Wade K. Aldous, Brooke Army Medical Center, Department of Pathology, 3851 Roger Brooke Drive, Fort Sam Houston, TX 78234-6200 (wade.aldous@us.army.mil). Received August 26, 2009; accepted September 27, 2009; electronically published February 24, 2010. Disclaimer: The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or reflecting the views of the Department of the Army, Department of Defense, or the US government. This work was prepared as part of their official duties, so no copyright is claimed.

The Inguinal Skin: An Important Site of Colonization with Extended‐Spectrum β‐Lactamase–Producing Enterobacteriaceae

Nosocomial fungal infections are gaining increased attention from infectiologists. An adequate investigation into the levels of airborne Aspergillus and other fungal spores in hospital settings, under normal conditions, is largely unknown. We monitored airborne spore contamination in a Swiss hospital building in order to establish a seasonally-dependent base-line level. Air was sampled using an impaction technique, twice weekly, at six different locations over one year. Specimens were seeded in duplicate on Sabouraud agar plates. Grown colonies were identified to genus levels. The airborne Aspergillus spore concentration was constantly low throughout the whole year, at a median level of 2 spores/m3 (inter-quartile range = IQR 1–4), and displayed no seasonal dependency. The median concentration of other fungal spores was higher and showed a distinct seasonal variability with the ambient temperature change during the different seasons: 82 spores/m3 (IQR 26–126) in summer and 9 spores/m3 (IQR 6–15) in winter. The spore concentration varied considerably between the six sampling sites in the building (10 to 26 spores/m3). This variability may explain the variability of study results in the literature.

Non-Seasonal Variation of Airborne Aspergillus Spore Concentration in a Hospital Building.

Bloodstream infections (are associated with high mortality. The incidence of bloodstream infections is increasing worldwide, with a shift towards multiresistant pathogens such as methicillin-resistant Staphylococcus aureus, enterococci and Candida spp. This study analysed retrospectively 1814 episodes of bacteraemia from 1993 to 1997 at a single tertiary care centre. True bloodstream infections was defined as clinical sepsis and positive blood culture without evidence for contamination of skin bacteria. Of the 1814 episodes, 380 (20.9%) were contaminated, resulting in 1434 true episodes of bloodstream infection. 42% were nosocomial bloodstream infections and one fourth were primary bloodstream infections. The incidence of bloodstream infections increased from 13.0/10,000 patient-days (1993) to 15.8/10,000 patient-days (1997). Mortality increased from 15.4% (1993) to 21% (1997) (p = 0.059). The five most frequently isolated microorganisms were Escherichia coli, Staphylococcus aureus, Streptococcus pneumoniae, coagulase-negative staphylococci and streptococci. The distribution of bacteria did not change over time from 1993 to 1998. Multiresistant bacteria such as methicillin-resistant Staphylococcus aureus, enterococci, Pseudomonas spp. and yeasts were isolated in less than 5% of episodes. In addition, there is a trend towards decreasing resistance, in contrast to most other institutions in Southern Europe and the US. Further analyses and studies are necessary to answer questions raised by this retrospective study.

Epidemiology of septicemias in a university hospital over 5 yeaars

Purpose Staphylococcus aureus bloodstream infections (SA BSI) are associated with substantial mortality. The rapid emergence of methicillin-resistant S. aureus (MRSA), known to be associated with worse outcome, may blur advances made regarding mortality attributed to SA BSI caused by methicillin-sensitive S. aureus (MSSA) strains. In the unusual setting of a very low MRSA prevalence institution, we investigated incidence, mortality and trends of BSI caused by MSSA over the last 20 years. Objective To evaluate and demonstrate trends in incidence and mortality of MSSA BSI as well as risk factors for mortality. Methods Retrospective, observational analysis of the prospective bloodstream infection cohort at the University Hospital Basel between January 1993 and December 2013. All patients with blood cultures positive for MSSA were included. All patients were analysed regarding pertinent demographic, clinical and antimicrobial treatment data. We calculated incidence, temporal trends and mortality of MSSA BSI. Results 1328 episodes of MSSA BSI were identified, accounting for a yearly incidence ranging from 2.1 to 4.5 per 10 000 patient-days (p = 0.2 for trend). Overall mortality was 19.3% and did not improve over time. Community-acquired MSSA BSI significantly increased over time, while nosocomial cases decreased (p Conclusions Mortality related to MSSA BSI remains high and unchanged over the last 20 years. Despite advances in treatment and supportive care in medicine during the last 20 years survival did not improve and, therefore, new approaches are required to lower mortality in MSSA BSI.

Reto Laffer

Papers

How to discriminate contamination from bloodstream infection due to coagulase-negative staphylococci: a prospective study with 654 patients.

The Inguinal Skin: An Important Site of Colonization with Extended‐Spectrum β‐Lactamase–Producing Enterobacteriaceae

Non-Seasonal Variation of Airborne Aspergillus Spore Concentration in a Hospital Building.

Epidemiology of septicemias in a university hospital over 5 yeaars

Survival from methicillin-sensitive Staphylococcus aureus bloodstream infections over 20 years: a cohort of 1328 patients.