Sepsis 2019: What Surgeons Need to Know.

The definition of sepsis continues to be as dynamic as the management strategies used to treat this. Sepsis-3 has replaced the earlier systemic inflammatory response syndrome (SIRS)-based diagnoses with the rapid Sequential Organ Failure Assessment (SOFA) score assisting in predicting overall prognosis with regards to mortality. Surgeons have an important role in ensuring adequate source control while recognizing the threat of carbapenem-resistance in gram-negative organisms. Rapid diagnostic tests are being used increasingly for the early identification of multi-drug-resistant organisms (MDROs), with a key emphasis on the multidisciplinary alert of results. Novel, higher generation antibiotic agents have been developed for resistance in ESKCAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) organisms while surgeons have an important role in the prevention of spread. The Study to Optimize Peritoneal Infection Therapy (STOP-IT) trial has challenged the previous paradigm of length of antibiotic treatment whereas biomarkers such as procalcitonin are playing a prominent role in individualizing therapy. Several novel therapies for refractory septic shock, while still investigational, are gaining prominence rapidly (such as vitamin C) whereas others await further clinical trials. Management strategies presented as care bundles continue to be updated by the Surviving Sepsis Campaign, yet still remain controversial in its global adoption. We have broadened our temporal and epidemiologic perspective of sepsis by understanding it both as an acute, time-sensitive, life-threatening illness to a chronic condition that increases the risk of mortality up to five years post-discharge. Artificial intelligence, machine learning, and bedside scoring systems can assist the clinician in predicting post-operative sepsis. The public health role of the surgeon is key. This includes collaboration and multi-disciplinary antibiotic stewardship at a hospital level. It also requires controlling pharmaceutical sales and the unregulated dispensing of antibiotic agents globally through policy initiatives to control emerging resistance through prevention.

Death from pan-resistant superbug

Acinetobacter baumannii has emerged as a pan-resistant superbug causing fatal infections in vulnerable patients. This report is the case of an immunosuppressed transplant patient with a fatal pneumonia due to pan-resistant Acinetobacter baumannii. Alternative therapy for resistant Acinetobacter infection is currently the subject of intense interest and research. This report illustrates the features of this type of emerging infectious disease and reviews some of the novel approaches to treatment.

Bloodstream infections caused by carbapenem-resistant Acinetobacter baumannii: Clinical features, therapy and outcome from a multicenter study.

OBJECTIVES: bloodstream infections (BSI) due to multidrug-resistant (MDR) Acinetobacter baumannii (AB) have been increasingly observed among hospitalized patients. METHODS: prospective, observational study conducted among 12 large tertiary-care hospitals, across 7 Italian regions. From June 2017 to June 2018 all consecutive hospitalized patients with bacteremia due to MDR-AB were included and analyzed in the study. RESULTS: During the study period 281 episodes of BSI due to MDR-AB were observed: 98 (34.8%) episodes were classified as primary bacteremias, and 183 (65.2%) as secondary bacteremias; 177 (62.9%) of them were associated with septic shock. Overall, 14-day mortality was observed in 172 (61.2%) patients, while 30-day mortality in 207 (73.6%) patients. On multivariate analysis, previous surgery, continuous renal replacement therapy, inadequate source control of infection, and pneumonia were independently associated with higher risk of septic shock. Instead, septic shock and Charlson Comorbidity Index >3 were associated with 14-day mortality, while adequate source control of infection and combination therapy with survival. Finally, septic shock, previous surgery, and aminoglycoside-containing regimen were associated with 30-day mortality, while colistin-containing regimen with survival. CONCLUSIONS: BSI caused by MDR-AB represents a difficult challenge for physicians, considering the high rates of septic shock and mortality associated with this infection.

Eradication of Acinetobacter baumannii/Enterobacter cloacae complex in an open proximal tibial fracture and closed drop foot correction with a multidisciplinary approach using the Taylor Spatial Frame®: a case report.

BACKGROUND: Multi-drug-resistant bacteria (e.g. Carbapenem-resistant Acinetobacter baumannii, extended-spectrum betalactamase or carbapenemase-producing enterobacteriaceae) are emerging in early-onset infections. So far, there is no report describing the eradication of these bacteria in a osseous infection of an open proximal tibial fracture in combination with the hexapod technology to address both osseous consolidation and closed drop foot correction. CASE PRESENTATION: After sustaining a proximal tibial fracture (Gustilo 3B), a 41-year-old man was primarily treated with open reduction and internal fixation by a locking plate and split-thickness skin graft in the home country. At the time of admission to our hospital there was a significant anterolateral soft tissue defect covered with an already-necrotic split-thickness graft and suspicious secretion. CAT and MRI scans revealed no signs of osseous healing, intramedullary distinctive osteomyelitis, as well as a large abscess zone in the dorsal compartment. Multiple wound smears showed multi-drug-resistant bacteria: Acinetobacter baumannii (Carbapenem resistant) as well as Enterobacter cloacae complex (AmpC overexpression). After implant removal, excessive osseous and intramedullary debridements using the Reamer Irrigator Aspirator (RIA®) as well as initial negative pressure wound therapy were performed. Colistin hand-modelled chains and sticks were applied topically as well as an adjusted systemic antibiotic scheme was applied. After repetitive surgical interventions, the smears showed bacterial eradication and the patient underwent soft tissue reconstruction with a free vascularized latissimus dorsi muscle flap. External fixation was converted to a hexapod fixator (TSF®) to correct primary varus displacement, axial assignment and secure osseous healing. A second ring was mounted to address the fixed drop foot in a closed fashion without further intervention. At final follow-up, 12 months after trauma, the patient showed good functional recovery with osseous healing, intact soft tissue with satisfactory cosmetics and no signs of reinfection. CONCLUSIONS: A multidisciplinary approach with orthopaedic surgeons for debridement, planning and establishing osseous and joint correction and consolidation, plastic surgeons for microvascular muscle flaps for soft tissue defect coverage as well as clinical microbiologists for the optimized anti-infective treatment is essential in these challenging rare cases. LEVEL OF EVIDENCE: Level IV.

Treatment of ventriculoperitoneal shunt infection and ventriculitis caused by Acinetobacter baumannii: a case report.

BACKGROUND: Acinetobacter baumannii (A. baumannii) infections are a recognized problem in healthcare, causing ventriculoperitoneal shunt infection and ventriculitis. Such infections are serious intracranial infection that can lead to serious complication and death. Treatment of infection caused by A. baumannii becomes difficult because of its inclination to develop pandrug resistance to the universally used antibiotics. In this case, we focused on pediatric ventriculitis/shunt infection caused by A. baumannii in an extensive follow-up and report the subsequent treatment outcome. Very limited information regarding the therapeutic options against A. baumannii ventriculitis/shunt infection is available in our hospital. Thus, we present one such case and the problems in its treatment. CASE PRESENTATION: We reported the case of a 6-year-old Ethiopian boy who developed ventriculitis/shunt infection from the pandrug-resistant strain of A. baumannii, after decompression of a craniotomy for medulloblastoma. Following the surgical procedure, he had developed hydrocephalus and ventriculoperitoneal shunt infection/ventriculitis as he presented with persistent fever, elevated white blood cell count, reduced glucose level, and the cerebrospinal fluid culture revealed A. baumannii, which was not responding to most of commercially available antibiotics systemically. Our patient was successfully treated with intravenous ampicillin-sulbactam. CONCLUSIONS: We presented our case of pandrug-resistant A. baumannii ventriculoperitoneal shunt infection and ventriculitis successfully treated with a systemic ampicillin-sulbactam. Provision of systemic ampicillin-sulbactam should not be undermined. Therefore, this case exemplifies that intravenous administration of ampicillin-sulbactam can be a good therapeutic option against A. baumannii ventriculoperitoneal shunt infection and ventriculitis.

Development and Use of Personalized Bacteriophage-Based Therapeutic Cocktails To Treat a Patient with a Disseminated Resistant Acinetobacter baumannii Infection.

Widespread antibiotic use in clinical medicine and the livestock industry has contributed to the global spread of multidrug-resistant (MDR) bacterial pathogens, including Acinetobacter baumannii We report on a method used to produce a personalized bacteriophage-based therapeutic treatment for a 68-year-old diabetic patient with necrotizing pancreatitis complicated by an MDR A. baumannii infection. Despite multiple antibiotic courses and efforts at percutaneous drainage of a pancreatic pseudocyst, the patient deteriorated over a 4-month period. In the absence of effective antibiotics, two laboratories identified nine different bacteriophages with lytic activity for an A. baumannii isolate from the patient. Administration of these bacteriophages intravenously and percutaneously into the abscess cavities was associated with reversal of the patient's downward clinical trajectory, clearance of the A. baumannii infection, and a return to health. The outcome of this case suggests that the methods described here for the production of bacteriophage therapeutics could be applied to similar cases and that more concerted efforts to investigate the use of therapeutic bacteriophages for MDR bacterial infections are warranted.

The role of surgery in necrotizing otitis externa.

This retrospective case review describes a subset of 5 patients with necrotizing otitis externa (NOE) with a refractory disease course who underwent surgery as part of their management plan between 2008 and 2013. Surgery promoted the cure of 4 of the 5 patients, and a fungal pathogen was recovered in 4 of 5 surgical samples. We conclude that surgery may be a necessary diagnostic and treatment adjunct in selective cases of NOE, especially in patients with a refractory disease course or with a suspected fungal etiology.

Potential of a lytic bacteriophage to disrupt Acinetobacter baumannii biofilms in vitro.

AIM: The ability of Acinetobacter baumannii to form biofilms and develop antibiotic resistance makes it difficult to control infections caused by this bacterium. In this study, we explored the potential of a lytic bacteriophage to disrupt A. baumannii biofilms. MATERIALS & METHODS: The potential of the lytic bacteriophage to disrupt A. baumannii biofilms was assessed by performing electron microscopy, live/dead bacterial staining, crystal violet staining and by determining adenosine triphosphate release. RESULTS: The bacteriophage inhibited the formation of and disrupted preformed A. baumannii biofilms. Results of disinfection assay showed that the lytic bacteriophage lysed A. baumannii cells suspended in blood or grown on metal surfaces. CONCLUSION: These results suggest the potential of the lytic bacteriophage to disrupt A. baumannii biofilms.

Characteristics and Outcomes of Acinetobacter baumannii Infections in Critically Ill Patients with Cancer: A Matched Case-Control Study.

AIM: To describe the characteristics and outcomes of Acinetobacter baumannii (AB) infections in critically ill cancer patients and to evaluate the impact of AB on mortality and length of stay (LOS). RESULTS: In a 4-year case-control study of critically ill cancer patients, we identified 161 patients with AB infections and 232 matched patients who were treated in the intensive care unit (ICU) during the same time period, but had no AB cultures. The case and control groups were matched for APACHE II, age, gender, type of malignancy, and mechanical ventilation. Most AB isolates were carbapenem-resistant (n=142, 88.2%). The majority of positive cultures were collected from the respiratory tract (58%) and blood (21.8%). The median ICU LOS and mortality rate for patients with AB infections were higher than those for the control group (12 days [IQR 6-23] vs. 3 days [IQR 1-7], p<0.0001 and 73.3% vs. 61.5%, p=0.015, respectively). AB infection was independently associated with ICU LOS and mortality: OR 1.108 (95% CI, 1.077-1.139), OR 1.658 (95% CI, 1.017-2.703), respectively. CONCLUSION: AB infections in critically ill cancer patients were independently associated with increased mortality and increased ICU LOS. Measures to improve the outcomes of critically ill cancer patients infected with AB are necessary.

SUCCESSFUL TREATMENT OF MULTIDRUG-RESISTANT ACINETOBACTOR BAUMANII BLISTERS ON THE KNEE.

Acinetobacter baumannii (A. baumannii), nosocomial infections, especially those due to multi-drug resistant (MDR) strains, are increasingly detected. This study reports the case of a 50-year-old man with blisters on the right knee for 8 months, first admitted through the outpatient department for incisional biopsy. Microbiological and histo-pathological examination confirmed the diagnosis of blisters extending deeply up to the knee joint caused by MDR- A. baumannii. A broad spectrum antibiotic therapy was administered and later readjusted according to the results of microbiological culture and biopsy report. Intensive hemodynamic support was required. An extensive surgical debridement was promptly performed and repeated until complete control of the infection with intravenous colistins. Blisters were excised; wounds were dressed daily with chlorhexidine dressings and polymyxine-impregnated dressing. Wounds were finally covered with split-thickness skin grafts. The infection was overcome 120 days after admission. The graft take was 40%. Postoperative rehabilitation was required because of the functional limitation of lower limb movements at the knee joint. Follow-up at 8 months showed no functional deficit and an acceptable aesthetic result. AB-MDR affecting soft tissues is a life-threatening disease, especially in patients with poor immunity and limited access to health facilities, whose clinical diagnosis may sometimes be challenging. Early recognition and treatment represent the most important factors influencing survival.

Bacterial infections following non-ablative fractional laser treatment: a case series and discussion.

Non-ablative fractional laser procedures have become increasingly popular since their introduction in 2004. The fractional 1,927 nm thulium laser is a non-ablative device that penetrates up to 300 µm in the skin and the 1,550 nm erbium:glass laser penetrates up to 1,400 µm. These procedures are considered minimally invasive with a high safety profile; therefore, infectious complications are exceedingly rare. However, we report five recent cases of bacterial infection with both gram-positive and gram-negative organisms following treatment with the fractional 1550/1927 nm laser approximately 1 day to 1 week post-procedure. One patient had a rapidly progressing pustular eruption with symptoms of sepsis. These patients were seen immediately, cultures were obtained and empiric antibiotic therapy was initiated. They recovered without long-term complications. Rapid-onset bacterial infections following non-ablative laser resurfacing with the 1550/1927 nm laser have not been previously reported in the literature. The infections can progress quickly and lead to serious sequelae, including systemic illness and severe scarring, if not identified and appropriately treated. We present these cases to highlight the importance of close surveillance and when appropriate, rapid intervention, following non-ablative fractional procedures, especially when patients present with atypical symptoms and signs.

Pulsed electric fields for burn wound disinfection in a murine model.

Emerging bacterial resistance renders many antibiotics ineffective, making alternative strategies of wound disinfection important. Here the authors report on a new, physical burn wound disinfection method: pulsed electric fields (PEFs). High voltage, short PEFs create nonthermal, permanent damage to cell membranes, possibly by irreversible electroporation. In medicine, PEF technology has recently been used for nonthermal ablation of solid tumors. The authors have expanded the spectrum of PEF applications in medicine to burn wound disinfection. A third-degree burn was induced on the dorsal skin of C57BL/6 mice. Immediately after the injury, the burn wound was infected with Acinetobacter baumannii expressing the luxCDABE operon. Thirty minutes after infection, the infected areas were treated with 80 pulses delivered at 500 V/mm, 70 µs, 1 Hz. The authors used bioluminescence to quantify bacteria on skin. Three animals were used for each experimental condition. PEFs were effective in the disinfection of infected burned murine skin. The bacterial load reduction correlated with the number of delivered pulses. Forty pulses of 500 V/mm led to a 2.04 ± 0.29 Log10 reduction in bacterial load; 80 pulses led to the immediate 5.53 ± 0.30 Log10 reduction. Three hours after PEF, the bacterial reduction of the skin treated with 500 V/mm, 80 pulses was 4.91 ± 0.71 Log10. The authors introduce a new method of wound disinfection using high voltage, short PEFs. They believe that PEF technology may represent an important alternative to antibiotics in addressing bacterial contamination of wounds, particularly those contaminated with multidrug-resistant bacteria.

Risk factors for nosocomial burn wound infection caused by multidrug resistant Acinetobacter baumannii.

Acinetobacter baumannii infections in burn patients may lead to delays in wound healing, graft losses, and development of sepsis. Determining the risk factors for multidrug resistant A. baumannii (MDR-AB) infections is essential for infection control. In the present study, the authors aimed to evaluate risk factors for wound infections caused by A. baumannii in burn patients. The study was conducted at Dicle University Hospital Burn Center, from April 2011 to July 2012, to investigate the risk factors for MDR-AB infections. The data of both the case and control group patients and the result of wound cultures were recorded on a daily basis, on individual forms given for each patient, and analyzed. A total of 30 cases infected with MDR-AB, and 60 uninfected control patients, were included in the study. The mean age (±SD) was 7.7 ± 15.4 years in infected patients and 11.4 ± 16.5 years in uninfected patients. The mean total burn surface area was 13.5 ± 10.9% in uninfected patients and 34.7 ± 16.2% in infected patients. The mean total burn surface area, the abbreviated burn severity index, acute physiological and chronic health evaluation II score, day of admission to hospital, length of hospital stay, first excision day, prior usage of third-generation cephalosporins, and stay in intensive care unit of the infected patients were significantly higher (P < .001) than those of patients without infection. Univariate analysis found that high acute physiological and chronic health evaluation II score, first excision time of wound, invasive device usage, admission day to hospital, and prior usage of broad-spectrum antibiotics were risk factors for nosocomial infections. This study showed that multiple factors contribute to multidrug resistance in A. baumannii. A combination of an early diagnosis of wound infections, appropriate antimicrobial treatments, surgical debridement, and early wound closure may be effective in the management.

[Lower respiratory tract infections related to Stenotrophomonas maltophilia and Acinetobacter baumannii]. / Infections bronchopulmonaires à Stenotrophomonas maltophilia et à Acinetobacter baumannii.

Stenotrophomonas maltophilia and Acinetobacter baumannii are both non-fermenting ubiquitous Gram-negative bacilli. The incidence of lower respiratory tract infections related to these microorganisms is increasing, especially in intensive care units. Their capacity to acquire resistance against several antimicrobials is challenging for clinicians and microbiologists. Despite their low virulence, these pathogens are responsible for colonization and infection in patients with comorbidities, immunosuppression, and critically ill patients. S. maltophilia and A. baumannii are mainly identified in nosocomial infections: ventilator-associated pneumonia, bacteremia and surgical wound infection. Infections related to these microorganism are associated with high mortality and morbidity. Trimethoprime-sulfamethoxazole and carbapenem are the first line treatment for infections related to S. maltophilia and A. baumannii respectively. However, the increasing rate of resistance against these agents results in difficulties in treating patients with infections related to these pathogens. New antimicrobial agents and further randomized studies are needed to improve the treatment of these infections. Prevention of spared of these multidrug-resistant bacteria is mandatory, including hand-hygiene, environment cleaning, and limited usage of large spectrum antibiotics.

[CSF otorrhea: case report and management]. / Le cas clinique du mois. Otorrhée cérébro-spinale: a partir d'un cas clinique, du diagnostic au traitement.

Mr G, sixty-seven years old, was admitted to our hospital for a liver transplant. He suffered from a cirrhosis due to an HBV infection, complicated by an hepatocellular carcinoma. During the perioperative care, a left otorrhea was discovered. According to the clinical history, this otorrhea had been present for six weeks and followed the completion of a myringotomy. The myringotomy had been performed with a view to place a transtympanic ventilation tube for the treatment of a serous otitis media inducing a conductive hearingloss. Clinical, biological, and radiological explorations revealed a CSF leak caused by the fact that the myringotomy had been done in a temporal meningo-encephalocele. A conservative treatment allowed to stop the otorrhea. We present a short discussion about temporal meningoencephalocele and, more generally, about CSF otorrhea.

Luminescent-activated transfected killer cells to monitor leukocyte trafficking during systemic bacterial and fungal infection.

BACKGROUND: Activated transfected killer (ATAK) cells are immortal phagocytes transfected with a luminescence reporter that effectively treat lethal infections in neutropenic mice. Their in vivo trafficking, lifespan, and immunogenicity are unknown. METHODS: Mice were made neutropenic; infected or not with Staphylococcus aureus, Acinetobacter baumannii, Candida albicans, or Aspergillus fumigatus; and treated intraperitoneally with ATAK cells. Cell trafficking and lifespan were assessed by in vivo imaging and reverse transcription-polymerase chain reaction. RESULTS: In uninfected neutropenic mice, ATAK cells spread from the mesentery into visceral organs on days 1-3. Splenic accumulation of ATAK cells increased at day 1 after infection with S. aureus and A. baumannii, and kidney accumulation increased in mice infected with C. albicans. Lung accumulation was seen at day 3 in mice infected by inhalation with A. fumigatus. By day 8, coincident with increasing anti-ATAK antibodies, luminescence signal was lost and there was no detectable mRNA transcription from ATAK cells. CONCLUSIONS: ATAK cells accumulated in target organs with distinct profiles, depending on the microbial etiology of infection. Finally, generation of an anti-ATAK immune response may provide an important safety mechanism that helps clear the cells from the host as the marrow recovers.

Novel therapies for treatment of multi-drug resistant Acinetobacter baumannii skin infections.

The Gram-negative coccobacillus Acinetobacter baumannii (Ab) has become an increasingly prevalent cause of hospital-acquired infections during the last two decades primarily resulting in pneumonia and complicated infections, including wound infections in troops injured in Afghanistan and Iraq. Moreover, the majority of clinical Ab isolates display high-level resistance to commonly utilized antimicrobial drugs, which severely compromises our capacity to care for patients with Ab disease. Thus, radically new approaches are urgently needed. This review focuses on novel therapies that can challenge the evolving ability of Ab to develop resistance and cause disease.

Management of an unfortunate triad after breast reconstruction: pyoderma gangrenosum, full-thickness chest wall defect and Acinetobacter Baumannii Infection.

If diagnosed late, post-surgical pyoderma gangrenosum (PSPG) is a rare, tricky and potentially life-threatening complication. Once diagnosed, immunosuppressive agents may provoke further complications. Well-intentioned extensive serial debridement may cause deep skin and soft-tissue defects, requiring skin grafting and possible flap surgery. The combination of necessary immunosuppressive treatment, protracted hospital stay and broad-spectrum systemic antimicrobial therapy may encourage serious acquired multidrug resistance (MDR). We report an unfortunate triad following breast reconstruction of PSPG, full-thickness chest wall defect and MDR with Acinetobacter baumannii infection. Interdisciplinary treatment using free flap surgery and negative-pressure wound therapy with instillation therapy (V.A.C.Instill(R) Wound Therapy) enabled survival and complete wound closure.

Septic arthritis of the knee caused by antibiotic-resistant Acinetobacter baumannii in a gout patient: a rare case report.

Over recent years, the incidence of infection caused by antibiotic-resistant Acinetobacter baumannii (a conditional pathogenic bacterium) has showed an increasing trend in such hospital departments as ICUs. Infections caused by antibiotic-resistant A. baumannii have drawn much attention from the medical professionals because it is difficult to manage such infections, and because the mortality related to such infections is high. To date, no cure of gouty arthritis and septic arthritis meanwhile complicated by antibiotic-resistant A. baumannii infection has been reported. We cured such a patient of intractable knee infection caused by A. baumannii resistant to all conventional antibiotics including imipenem by taking comprehensive measures including surgery, and infection did not recur during the 14-month follow-up.