Phenotypic and genotypic characteristics of a carbapenem-resistant Serratia marcescens cohort and outbreak: describing an opportunistic pathogen.

Serratia marcescens is an emerging opportunistic pathogen with high genetic diversity. This article describes the microbiological characteristics of isolates and the risk factors for infections caused by carbapenem-resistant S. marcescens. A retrospective study of patients colonized (n=43) and infected (n=20) with carbapenem-resistant S. marcescens over a 3-year period was conducted. Polymerase chain reaction for carbapenemase genes and molecular typing of all available strains was performed. Forty-two isolates were analysed, including three environmental samples identified during an outbreak. Thirty-five carbapenem-resistant S. marcescens carried blaKPC-2, one isolate was blaNDM-positive and four isolates carried blaOXA-101. The genomes were grouped into three clusters with 100% bootstrap; three patterns of mutations on ompC and ompF were found. The strains carried virulence genes related to invasion and haemolysis, and the environmental strains presented fewer mutations on the virulence genes than the clinical strains. Multi-variate analysis showed that previous use of polymyxin (P=0.008) was an independent risk factor for carbapenem-resistant S. marcescens infection. This study highlighted that blaKPC-2 in association with ompC or ompF mutation was the most common mechanism of resistance in the study hospital, and that previous use of polymyxin was an independent risk factor for carbapenem-resistant S. marcescens. There was a predominant clone, including the environmental isolates, suggesting that cross-transmission was involved in the dissemination of this pathogen.

Using ceftazidime-avibactam for persistent carbapenem-resistant Serratia marcescens infection highlights antimicrobial stewardship challenges with new beta-lactam-inhibitor combination antibiotics.

The newer beta-lactam-inhibitor combination (BLIC) antibiotics are available in South Africa (SA) for the treatment of carbapenem-resistant Enterobacterales infections. We describe the successful use of ceftazidime-avibactam (CA) for the treatment of a child with persistent carbapenem-resistant Serratia marcescens bacteraemia, and the challenges faced using this lifesaving antibiotic, including access to susceptibility testing, procurement process, cost and complexity of deciding when, how and for how long to use it. Furthermore, the burden of carbapenem resistance is increasing in SA, and inappropriate use of CA and other newer BLIC antibiotics, such as ceftolozane-tazobactam, will inevitably endanger their longevity. A careful balance must be struck between removing unnecessary obstacles and delays in initiating these antibiotics for life-threatening infections, and additional antimicrobial stewardship-guided interventions aimed at preserving their therapeutic use.

Exit site infection and peritonitis due to Serratia species in patients receiving peritoneal dialysis: Epidemiology and clinical outcomes.

AIM: To study the epidemiology and clinical outcomes of catheter-related infections of Serratia species in peritoneal dialysis (PD) patients. METHODS: We retrospectively reviewed the patient characteristics, antibiotics susceptibility/resistance patterns and treatment outcomes of exit site infection (ESI) and peritonitis due to Serratia in PD patients during the period of 2004 to 2017. RESULTS: One hundred and sixty-one patients had Serratia ESI, of which 10 (6.2%) progressed to tunnel tract involvement and 11 (6.8%) developed PD peritonitis. Nineteen (11.8%) patients with Serratia ESI failed to respond to medical treatment and required catheter removal. Fifty-six (34.8%) patients had repeat Serratia ESI, which occurred at 12.9 ± 13.6 months after the previous episode. Twenty-two patients had Serratia peritonitis, which accounted for 1% of peritonitis during the study period. Ten (45.5%) patients responded to medical treatment while 12 (54.5%) patients required catheter removal. Nine patients (36.4%) failed to resume PD and were converted to long-term haemodialysis. Two patients had repeat peritonitis at 2 months and 3 years, respectively, after the initial episode. Serratia species in PD patients showed high rates of resistance to ampicillin, and first- and second-generation cephalosporins, but were generally susceptible to aminoglycosides, carboxy-/ureido-penicillins and carbapenems. CONCLUSION: Our results suggest that Serratia ESI show low risk of progression to peritonitis and favourable response to medical therapy, while Serratia peritonitis was associated with high rates of catheter removal and peritoneal failure.

Dauer life stage of Caenorhabditis elegans induces elevated levels of defense against the parasite Serratia marcescens.

Host-parasite research often focuses on a single host life stage, yet different life stages may exhibit different defenses. The nematode Caenorhabditis elegans has an alternate dispersal life stage, dauer. Despite dauer's importance in nature, we know little of how it responds to parasites. Previous research indicates that non-dauer C. elegans prefer to consume the virulent bacterial parasite, Serratia marcescens, when given a choice between the parasite and benign Escherichia coli. Here, we compared the preferences of dauer individuals from six strains of C. elegans to the preferences of other life stages. We found that dauer individuals exhibited reduced preference for S. marcescens, and dauers from some strains preferred E. coli to S. marcescens. In addition to testing food preference, a mechanism of parasite avoidance, we also measured host mortality rates after direct parasite exposure to determine if life stage also altered host survival. Overall, dauer individuals exhibited reduced mortality rates. However, dauer versus non-dauer larvae mortality rates also varied significantly by host strain. Collectively, we found evidence of dauer-induced parasite avoidance and reduced mortality in the presence of a parasite, but these effects were strain-specific. These results demonstrate the importance of host life stage and genotype when assessing infection dynamics.

Outbreaks of Serratia marcescens and Serratia rubidaea bacteremia in a central Kathmandu hospital following the 2015 earthquakes.

Background: Human infections with Serratia spp. are generally limited to Serratia marcescens and the Serratia liquefaciens complex. There is little data regarding the infections caused by the remaining Serratia spp., as they are seldom isolated from clinical specimens. Methods: In this health care setting in Kathmandu, Nepal routine blood culture is performed on all febrile patients with a temperature >38°C or when there is clinical suspicion of bacteremia. During 2015 we atypically isolated and identified several Serratia spp. We extracted clinical data from these cases and performed whole genome sequencing on all isolates using a MiSeq system (Ilumina, San Diego, CA, USA). Results: Between June and November 2015, we identified eight patients with suspected bacteremia that produced a positive blood culture for Serratia spp., six Serratia rubidaea and five Serratia marcescens. The S. rubidaea were isolated from three neonates and were concentrated in the neonatal intensive care unit between June and July 2015. All patients were severely ill and one patient died. Whole genome sequencing confirmed that six Nepalese S. rubidaea sequences were identical and indicative of a single-source outbreak. Conclusions: Despite extensive screening we were unable to identify the source of the outbreak, but the inferred timeline suggested that these atypical infections were associated with the aftermath of two massive earthquakes. We speculate that deficits in hygienic behavior, combined with a lack of standard infection control, in the post-earthquake emergency situation contributed to these unusual Serratia spp. outbreaks.

Pathogenic bacteria enhance dispersal through alteration of Drosophila social communication.

Pathogens and parasites can manipulate their hosts to optimize their own fitness. For instance, bacterial pathogens have been shown to affect their host plants' volatile and non-volatile metabolites, which results in increased attraction of insect vectors to the plant, and, hence, to increased pathogen dispersal. Behavioral manipulation by parasites has also been shown for mice, snails and zebrafish as well as for insects. Here we show that infection by pathogenic bacteria alters the social communication system of Drosophila melanogaster. More specifically, infected flies and their frass emit dramatically increased amounts of fly odors, including the aggregation pheromones methyl laurate, methyl myristate, and methyl palmitate, attracting healthy flies, which in turn become infected and further enhance pathogen dispersal. Thus, olfactory cues for attraction and aggregation are vulnerable to pathogenic manipulation, and we show that the alteration of social pheromones can be beneficial to the microbe while detrimental to the insect host.Behavioral manipulation of host by pathogens has been observed in vertebrates, invertebrates, and plants. Here the authors show that in Drosophila, infection with pathogenic bacteria leads to increased pheromone release, which attracts healthy flies. This process benefits the pathogen since it enhances bacterial dispersal, but is detrimental to the host.

Serratia marcescens Bullous Cellulitis in a Splenectomized Patient: A Case Report and Review of the Literature.

Serratia marcescens is a Gram-negative bacillus belonging to the Enterobacteriaceae family. Cutaneous infection with Serratia is rare, and usually occurs in immunocompromised individuals. Primary cutaneous infections are uncommon, but they are typically severe and are associated with significant morbidity and mortality. The pathogenetic factors leading to S. marcescens infection are not fully understood, but contributing virulence factors include proteases, secreted exotoxins, and the formation of biofilm. We report a case of cellulitis occurring in a splenectomized patient, which led to multiple wound debridements and a transmetatarsal amputation. This dramatic case led us to review the published literature on soft tissue infections caused by S. marcescens.

[Corneal ulcer caused by Serratia marcescens: case report].

A case of corneal ulcer caused by Serratia marcescens is reported in a patient with history of corneal microtrauma. Biological features (pathogenicity factors, antibiotic resistance) of isolated culture were characterized. Keratitis cases caused by this agent were analyzed.

Spontaneous perforation of the tympanic membrane in the first 10 days of life.

Twelve cases of neonates admitted to the neonatal unit of our hospital, between January 1, 2000, and December 31, 2005, because of otorrhea due to spontaneous perforation of the tympanic membrane within the first 10 days of life are presented. Data were collected retrospectively from medical records. Cultures of the middle ear exudate grew PSEUDOMONAS AERUGINOSA in 10, SERRATIA MARCENSCENS in 1, and STAPHYLOCOCCUS AUREUS in 1 neonate. Cultures of nasopharyngeal secretions grew P. AERUGINOSA in nine, S. MARCENSCENS in one, S. AUREUS in one, and STREPTOCOCCUS VIRIDANS in one neonate. Middle ear versus nasopharyngeal secretions cultures grew the same organism in 11 neonates. A 10-day course of parenteral antibiotics was administered (ampicillin-ceftazidime for all neonates except for the one neonate with the S. AUREUS otitis who received netilmicin-cloxacillin). All neonates had uneventful course and were discharged home in good clinical condition. Our findings suggest that neonates with eardrum perforation should receive antibiotics parenterally, as the most common pathogens is P. AERUGINOSA, for which there are no satisfactory antibiotics for oral use.

Clinical and histopathological features and a unique spectrum of organisms significantly associated with chronic granulomatous disease osteomyelitis during childhood.

Herein, we describe a combination of clinical, microbiologic, and histopathologic findings significantly associated with osteomyelitis in chronic granulomatous disease. When present, these features should raise the suspicion of underlying chronic granulomatous disease. In patients with these findings, anti-infective prophylactic measures aiming to cover highly prevalent microorganisms, as well as aggressive therapeutic measures, should be strongly encouraged.

A model of bacterial intestinal infections in Drosophila melanogaster.

Serratia marcescens is an entomopathogenic bacterium that opportunistically infects a wide range of hosts, including humans. In a model of septic injury, if directly introduced into the body cavity of Drosophila, this pathogen is insensitive to the host's systemic immune response and kills flies in a day. We find that S. marcescens resistance to the Drosophila immune deficiency (imd)-mediated humoral response requires the bacterial lipopolysaccharide O-antigen. If ingested by Drosophila, bacteria cross the gut and penetrate the body cavity. During this passage, the bacteria can be observed within the cells of the intestinal epithelium. In such an oral infection model, the flies succumb to infection only after 6 days. We demonstrate that two complementary host defense mechanisms act together against such food-borne infection: an antimicrobial response in the intestine that is regulated by the imd pathway and phagocytosis by hemocytes of bacteria that have escaped into the hemolymph. Interestingly, bacteria present in the hemolymph elicit a systemic immune response only when phagocytosis is blocked. Our observations support a model wherein peptidoglycan fragments released during bacterial growth activate the imd pathway and do not back a proposed role for phagocytosis in the immune activation of the fat body. Thanks to the genetic tools available in both host and pathogen, the molecular dissection of the interactions between S. marcescens and Drosophila will provide a useful paradigm for deciphering intestinal pathogenesis.

Prostaglandins, not lipoxygenase products, mediate insect microaggregation reactions to bacterial challenge in isolated hemocyte preparations.

Nodulation is the predominant cellular defense reaction to bacterial challenge in insects. Eicosanoids mediate several steps in the nodulation process, including formation of hemocyte microaggregations. Isolated hemocyte preparations synthesize and secrete eicosanoids, which mediate hemocytic immune reactions. Two major groups of eicosanoids are prostaglandins (products of cyclooxygenase pathways) and various products of lipoxygenase pathways. In this study, we test the hypothesis that prostaglandins, but not lipoxygenase products, mediate hemocyte microaggregation reactions in response to bacterial challenge. Our results indicate that isolated hemocyte preparations pretreated with the cyclooxygenase inhibitors indomethacin and naproxen yielded fewer microaggregates than untreated control groups (3.7 x 10(5) microaggregates/ml hemolymph vs. 11.0 x 10(5) microaggregates/ml hemolymph). These inhibitors influence hemocyte microaggregate formation in a dose-dependent manner in treatments ranging from 0 to 200 microM. The lipoxygenase inhibitors esculetin and caffeic acid did not impact the formation of microaggregates in this system. The influence of the phospholipase A(2) inhibitor dexamethasone was reversed by amending experimental (dexamethasone-treated) preparations with prostaglandin H(2), but not prostaglandin D(2), prostaglandin E(2), nor 5(S)-hydroperoxy-6E,8Z,11Z,14Z-eicosatetraenoic acid, a product of the lipoxygenase pathway. We infer that prostaglandins are the primary mediators of microaggregation reactions to bacterial challenge in insect hemocyte preparations.

Eicosanoid involvement in the regulation of behavioral fever in the desert locust, Schistocerca gregaria.

The desert locust Schistocerca gregaria behaviorally thermoregulates in order to try and maintain a favoured "set point" body temperature. Locusts infected with the deuteromycete fungal pathogen Metarhizium anisopliae var acridumchoose a significantly elevated temperature. This "behavioral fever" greatly delays the progress of mycosis. We have confirmed this phenomenon and shown that desert locusts also fever when infected with the bacterial pathogen Serratia marcescens. Elevation in the prefered environmental temperature occurs also upon injection with laminarin and lipopolysaccharide (microbial cell wall components). Since such treatments also stimulate the immune system it would appear that "behavioral fever" is probably a feature of the immune response. The eicosanoid biosynthesis inhibitor dexamethasone prevented laminarin invoked fever. This effect was reversable by arachidonic acid. Therefore in common with the febrile response in mammals behavioral fever in insects may be mediated locally by circulating eicosanoids.

Eicosanoids act in nodulation reactions to bacterial infections in newly emerged adult honey bees, Apis mellifera, but not in older foragers.

Nodulation is the first, and qualitatively predominant, cellular defense reaction to bacterial infections in insects. We tested the hypothesis that eicosanoids also mediate nodulation reactions to bacterial challenge in adults of a social insect, the honey bee, Apis mellifera. Treating newly-emerged experimental bees with the eicosanoid biosynthesis inhibitor, dexamethasone, impaired nodulation reactions to bacterial infections, and the influence of dexamethasone was reversed by treating infected insects with arachidonic acid, an eicosanoid precursor. Several other eicosanoid biosynthesis inhibitors, including the cyclooxygenase inhibitor, indomethacin, and the dual cyclooxygenase/lipoxygenase inhibitor, phenidone, also impaired the ability of experimental honeybees to form nodules in reaction to bacterial challenge. The influence of phenidone on nodulation was expressed in a dose-dependent manner. However, in experiments with older honey bees foragers, similar bacterial challenge did not evoke nodulation reactions. We infer from our results that while eicosanoids mediate cellular immune responses to bacterial infections in newly emerged honey bees, and more broadly, in most insect species, nodulation reactions to bacterial challenge probably do not occur in all phases of insect life cycles.

Protective effect of a lipoxygenase inhibitor, nordihydroguaretic acid, on the ileal motor disturbances induced by Serratia marcescens endotoxin in rats.

This study was conducted to examine the effects of peptidoleukotrienes on the ileal contractility disturbances induced by Serratia marcescens endotoxin in rats. Thirty-two male Wistar rats were divided into four groups (n = 8 each). The first group was given only an anesthetic agent (control group); the second group was given the endotoxin (endotoxin group); the third group was given a lipoxygenase inhibitor, nordihydroguaretic acid (NDGA); and the fourth group was given NDGA 10 min before administration of the endotoxin (NDGA+endotoxin group). The isolated ileum response was recorded in each group. Normal contractile activity was seen in the control group. After the endotoxin was given. the isolated ileum did not respond to 497acetylcholine (ACh) in the endotoxin group, but the contractile results of isolated ileum to ACh were similar to the control group results in both the NDGA and endotoxin+NDGA groups. The results of this study demostrate that leukotrienes may play a role in endotoxin-induced ileal contractility disturbances, and that the lipoxygenase inhibitor, NDGA, could be useful for the treatment of ileal motility disturbances induced by endotoxin.

Endophthalmitis caused by Serratia marcescens.

BACKGROUND AND OBJECTIVE: To describe the clinical features and treatment outcomes of 10 patients with culture-proven Serratia marcescens endophthalmitis. PATIENTS AND METHODS: Records from the microbiology laboratory for the period from January 1980 through June 1993 were reviewed. Ten patients were identified who had positive anterior chamber or vitreous cultures and clinical signs of endophthalmitis. The medical records for these 10 patients were reviewed, and the patients were contacted for reexamination when possible. RESULTS: All 10 cases of S. marcescens endophthalmitis occurred after ocular surgery. Eight eyes received intraocular antibiotics and 2 eyes were primarily enucleated or eviscerated. All organisms were sensitive to aminoglycosides and to ceftazidime. Repeat vitreous cultures were positive in 5 cases despite appropriate initial therapy with intravitreal and intravenous antibiotics. Final visual acuity was 20/400 or better in 4 of 10 eyes. A total of 4 eyes were enucleated or eviscerated at final follow-up. Eyes with light perception or better visual acuity had a mean follow-up of 23 months. CONCLUSION: S. marcescens can cause persistent endophthalmitis despite appropriate intravitreal and systemic antibiotic therapy. Eyes with S. marcescens endophthalmitis have a poor visual prognosis.

Spontaneous healing of a massive tibial cortical defect.

This case report describes the spontaneous healing of a 20-cm massive tibial cortical defect. The defect was created during debridement of necrotic bone and soft tissue in a low-velocity gunshot wound of the tibia that became infected in a skeletally mature patient. The patient was treated in an external fixator and had a soleus flap to provide soft-tissue coverage. He had refused any surgical reconstructive options. Despite the absence of surgical reconstruction, his tibia healed, and he returned to full activity without any orthotic device 9 months after the original injury.