In the Literature

ENTEROCOCCI : HOW THEY GOT THAT WAY

Lebreton F, Manson AL, Saavedra JT, Straub TJ, Earl AM, Gilmore MS. Tracing the enterococci from Paleozoic origins to the hospital. Cell 2017; 169:849–61.

Although enterococci ordinarily account for <0.1% of the human gastrointestinal microbiota, they have managed to emerge as the perhaps the best hospital-adapted multidrug-resistant pathogens among all their companions. Lebreton and colleagues have examined the evolutionary history of these organisms to explain this success.

The investigators examined 2 dozen enterococcal species representing all the major phylogenetic branches of the genus. Using modern isolates, they utilized molecular clock estimation and also examined their distribution in the environment, phenotypic diversity, and host fossil records. They concluded that enterococci first emerged 425–500 million years ago from ancestral Vagococcus lutrae—more than 200 million years before the appearance of dinosaurs, but about the same time that land-adapted animals appeared.

Since their divergence from their common ancestor, enterococci acquired 126 genes in the core genome that are related to “hardening” of its cell wall and response to stress, and were presumably selected as a consequence of stress exposures in a new environment. Phenotypic analysis demonstrated that a characteristic distinguishing these organisms from their common ancestor is their survival under harsh conditions including exposure to solvents, detergents, antibiotics, and biocides as well as resistance to desiccation and starvation. These characteristics undoubtedly contribute to the persistence of enterococci in the hospital environment. Notably, Enterococcus faecium was the most tolerant to starvation among all the species.

Enterococci are widely distributed among land animals, including birds, mammals, reptiles, and even insects, and their speciation paralleled the evolutionary diversification of these hosts. Genetic evidence indicated that a major driver of speciation in enterococci was changing carbohydrate utilization in terrestrial host gastrointestinal tracts.

Thus, the investigators conclude that the modern success of enterococci began with events >400 million years ago. Their successful colonization of the gastrointestinal tracts of terrestrial animals, together with genetic evolution enabling survival in the environment into which it was constantly shed from the fecal stream of those animals, foreshadowed its survival in hospital environments as well as its ability to resist antibiotics.

CEREBROSPINAL FLUID NEUTROPHILIC PLEOCYTOSIS IN VIRAL INFECTIONS OF THE CENTRAL NERVOUS SYSTEM: DOES IT MATTER?

Jaijakul S, Salazar L, Wootton SH, et al. The clinical significance of neutrophilic pleocytosis in cerebrospinal fluid in patients with viral central nervous system infections. Int J Infect Dis 2017; 59:77–81.

Neutrophilic cerebrospinal fluid (CSF) pleocytosis is ordinarily associated with bacterial causes of meningitis, but this finding may also be encountered in viral meningitis, particularly early in the course. In one report, while 38 patients with central nervous system (CNS) infections due to varicella zoster virus (one-fourth with encephalitis) in whom the median total white blood cell count (WBC) was 150 cells/mm³, the median proportion that were neutrophils was only 3% (interquartile range [IQR], 1–32) [1]. Those with enterovirus infection, in contrast, had a median of 30% neutrophils (IQR, 10–69) of a total median CSF WBC of 105 cells/mm³—an expected finding because of a known propensity toward CSF neutrophilic pleocytosis in enteroviral meningitis. Enterovirus, however, is not alone in this regard. Tyler and colleagues found that in 174 patients with meningitis due to this West Nile virus, there were >50% neutrophils in 45.6% of cases [2]. In fact, 17.2% had >75% of neutrophils.

The presence of CSF neutrophilic pleocytosis in patients with viral meningitis complicates their initial management and may lead to unnecessary and inordinately prolonged antibacterial administration. Jaijakul and colleagues examined another aspect of this issue by assessing whether neutrophilic pleocytosis is associated with adverse outcomes in patients with viral CNS infection.

In their retrospective analysis, the investigators examined the records of 182 patients with viral CNS infections and found that 45 (24.7%) had CSF neutrophilic pleocytosis, defined as >50% of WBC being neutrophils. Neutrophilic pleocytosis was seen in 64% of enterovirus infections, 20% of those due to herpesviruses (herpes simplex and varicella zoster), and in 16% of arbovirus (West Nile and St Louis encephalitis virus) infections. An adverse outcome occurred in 29 (15.9%) patients. The only independent risk factor for an adverse outcome was the presence of encephalitis; neutrophilic pleocytosis was not a predictor of adverse outcomes.

References

ANTIBIOTIC RESISTANCE: THE POTENTIAL ROLE OF BACTERIOPHAGE “SUPERSPREADERS”

Keen EC, Bliskovsky VV, Malagon F, et al. Novel “superspreader” bacteriophages promote horizontal gene transfer by transformation. MBio 2017; 8. doi:10.1128/mBio.02115-16.

Bacteriophages commonly carry genes encoding antibiotic resistance and are known to transfer that resistance to bacteria by transduction. As an example, the primary means of acquisition of antibiotic resistance genes (as well as virulence genes) by Staphylococcus are transduction and conjugation [1]. Resistance genes may also be acquired by transformation, a mechanism by which bacteria acquire DNA directly from their environment. Upon lysis by bacteriophage, bacteria release their contents, including plasmids, into their surroundings, but it has been unknown whether the plasmids, many of which may carry antibiotic resistance genes, are degraded or are released intact. In the case of the release of intact plasmids, there is an opportunity for uptake by other bacteria by transformation, potentially resulting in the horizontal transfer of resistance.

Keen and colleagues examined this issue, beginning with their evaluation of a library of lytic phages that are capable of infecting Escherichia coli strain MG1655. Among these, they identified 2 that promoted extensive plasmid transformation (indicating uptake of intact plasmids) in vitro and sequenced their entire genomes. Further evidence suggests that this bacteriophage “superspreader” phenotype may be the consequence of the absence of genes encoding hydrolytic endonucleases with the result that plasmid (and chromosomal) DNA is left intact.

Individual bacteriophages generally have highly restricted host ranges. The mechanism described by Keen and colleagues, however, overcomes this restriction, potentially facilitating the spread of antimicrobial resistance by release of intact plasmids to potential uptake by a wide range of bacteria, depending not on the host range of the phage but by that of the released plasmids.

The investigators point out that the phenomenon of superspreaders has significant implications for the ever-emerging field of phage therapy. They recommend that phages being considered for therapeutic use first be screened to eliminate any superspreader phage.

Reference

CASE VIGNETTE: HEATER-COOLER SYSTEMS STRIKE AGAIN—LEFT VENTRICULAR ASSIST DEVICE INFECTIONS WITH MYCOBACTERIUM CHIMAERA

Balsam LB, Louie E, Hill F, et al. Mycobacterium chimaera left ventricular assist device infections. J Card Surg 2017; 32:402–4.

A 70-year-old man underwent placement of a left ventricular assist device (LVAD) via a median sternotomy on normothermic cardiopulmonary bypass and then underwent repeat sternotomy 5 weeks later because of a mechanical LVAD complication. Seventeen months after LVAD implantation, he presented with 3 areas of fluctuance in the upper and mid-abdominal wall with fluid collections contiguous with the device within the pump pocket. He underwent drainage and debridement; routine bacterial cultures were negative. Despite administration of vancomycin and piperacillin-tazobactam and coverage with an omental flap, he returned 1 month later with an additional abdominal wall fluid collection from which Mycobacterium chimaera was recovered several weeks later. Treatment was changed to azithromycin, ethambutol, and rifampin with control for the subsequent several months of follow-up.

At the same hospital, a 53-year-old man also underwent LVAD placement via median sternotomy while on normothermic cardiopulmonary bypass. The original LVAD was exchanged 4 years after insertion and 1 year after this exchange he presented with a drive-line infection. The contiguous fluid collection was drained percutaneously and microscopic detection of acid-fast bacilli led to initiation of therapy with azithromycin, ethambutol, and rifampin; M. chimaera was subsequently recovered in culture. He underwent surgical debridement with delayed flap coverage of hardware but had recurrence within several weeks necessitating drainage.

The international outbreak of M. chimaera infections in patients who had undergone cardiovascular surgery while on cardiopulmonary bypass has been firmly traced to contamination of heater-cooler systems (LivaNova, formerly Sorin) during manufacture at a single production facility. Prevention involves using alternative heater-cooler systems and, if not possible, applying a number of recommended mitigations [1].

LVAD infections due to M. chimaera have previously been reported as part of case series but have not been described in detail [1]. These infections raise some important management issues, such as the potential value of device exchange. Also important is whether LVAD infection with M. chimaera should preclude cardiac transplantation.

References