Phage Therapy of Mycobacterium Infections: Compassionate Use of Phages in 20 Patients With Drug-Resistant Mycobacterial Disease.

BACKGROUND: Nontuberculous Mycobacterium infections, particularly Mycobacterium abscessus, are increasingly common among patients with cystic fibrosis and chronic bronchiectatic lung diseases. Treatment is challenging due to intrinsic antibiotic resistance. Bacteriophage therapy represents a potentially novel approach. Relatively few active lytic phages are available and there is great variation in phage susceptibilities among M. abscessus isolates, requiring personalized phage identification. METHODS: Mycobacterium isolates from 200 culture-positive patients with symptomatic disease were screened for phage susceptibilities. One or more lytic phages were identified for 55 isolates. Phages were administered intravenously, by aerosolization, or both to 20 patients on a compassionate use basis and patients were monitored for adverse reactions, clinical and microbiologic responses, the emergence of phage resistance, and phage neutralization in serum, sputum, or bronchoalveolar lavage fluid. RESULTS: No adverse reactions attributed to therapy were seen in any patient regardless of the pathogen, phages administered, or the route of delivery. Favorable clinical or microbiological responses were observed in 11 patients. Neutralizing antibodies were identified in serum after initiation of phage delivery intravenously in 8 patients, potentially contributing to lack of treatment response in 4 cases, but were not consistently associated with unfavorable responses in others. Eleven patients were treated with only a single phage, and no phage resistance was observed in any of these. CONCLUSIONS: Phage treatment of Mycobacterium infections is challenging due to the limited repertoire of therapeutically useful phages, but favorable clinical outcomes in patients lacking any other treatment options support continued development of adjunctive phage therapy for some mycobacterial infections.

Emergence of Dalbavancin, Vancomycin, and Daptomycin Nonsusceptible Staphylococcus aureus in a Patient Treated With Dalbavancin: Case Report and Isolate Characterization.

A patient with end-stage renal disease received 2 doses of dalbavancin for methicillin-resistant Staphylococcus aureus (MRSA) arteriovenous fistula infection and presented 5 weeks later with infective endocarditis secondary to vancomycin, daptomycin, and dalbavancin nonsusceptible MRSA. Resistance was associated with walK and scrA mutations, reduced long-chain lipid content, and reduced membrane fluidity.

The effect of a prospective intervention program with automated monitoring of hand hygiene performance in long-term and acute-care units at a Veterans Affairs medical center.

OBJECTIVE: To measure the impact of an automated hand hygiene monitoring system (AHHMS) and an intervention program of complementary strategies on hand hygiene (HH) performance in both acute-care and long-term care (LTC) units. DESIGN: Prospective, nonrandomized, before-and-after intervention study. SETTING: Single Veterans Affairs Medical Center (VAMC), with 2 acute-care units and 6 LTC units. METHODS: An AHHMS that provides group HH performance rates was implemented on 8 units at a VAMC from March 2021 through April 2022. After a 4-week baseline period and 2.5-week washout period, the 52-week intervention period included multiple evidence-based components designed to improve HH compliance. Unit HH performance rates were expressed as the number of dispenses (events) divided by the number of patient room entries and exits (opportunities) × 100. Statistical analysis was performed with a Poisson general additive mixed model. RESULTS: During the 4-week baseline period, the median HH performance rate was 18.6 (95% CI, 16.5-21.0) for all 8 units. During the intervention period, the median HH rate increased to 21.6 (95% CI, 19.1-24.4; P < .0001), and during the last 4 weeks of the intervention period (exactly 1 year after baseline), the 8 units exhibited a median HH rate of 25.1 (95% CI, 22.2-28.4; P < .0001). The median HH rate increased from 17.5 to 20.0 (P < .0001) in LTC units and from 22.9 to 27.2 (P < .0001) in acute-care units. CONCLUSIONS: The intervention was associated with increased HH performance rates for all units. The performance of acute-care units was consistently higher than LTC units, which have more visitors and more mobile veterans.

The andes of bladder stones: Gigantic bladder calculi in a patient with bladder outlet obstruction and hyperparathyroidism.

60-year-old man with known chronic urinary retention (CUR) managed with clean intermittent catheterization (CIC); He presented with difficulty with CIC. A KUB revealed 13 cm in conglomeration bladder stones. Routine preoperative bloodwork revealed calcium >12 and a subsequent PTH was also elevated. Osteoporosis was confirmed on DEXA. Sestamibi parathyroid scan had increased uptake within one parathyroid gland. The patient underwent open suprapubic 92 gm prostatectomy with evacuation of 254 gm calcium phosphate bladder stones; this was followed by removal of the offending parathyroid gland. On follow up, the patient was voiding well with normalization of other symptoms related to hyperparathyroidism.

Xanthogranulomatous pyelonephritis - A diagnostic and therapeutic dilemma.

Xanthogranulomatous pyelonephritis (XGP) is a rare variant of chronic pyelonephritis, occurring in the setting of obstructive uropathy and recurrent urinary tract infections (UTIs). It is difficult to diagnose as it can be asymptomatic until late-stage disease. Localized symptoms such as flank pain and dysuria may be attributed to nephrolithiasis or UTIs without prompting need for further workup. Extrarenal manifestations, most notably fistula formation, may present distal to the kidney and not be readily attributed to a renal pathology. The only known definitive therapy is nephrectomy. A delay in diagnosis can lead to fulminant complications or a more technically difficult nephrectomy. We present three cases of XGP, which serve to highlight the possibility of earlier diagnosis and resultant management options, including the potential for nephron-saving strategies. Early clinical and radiologic suspicion through awareness of risk factors may play an important role in preventing disease progression, avoiding late-stage complications, and improving treatment outcomes.

Whistling Scrotum: An Unusual Presentation of Pneumomediastinum in the Setting of an Open Scrotal Wound.

BACKGROUND Pneumoscrotum is a rare clinical occurrence in which air accumulates in the scrotum. The origin of air is primarily from trauma, but spontaneous pneumoscrotum can develop from gastrointestinal or pulmonary sources. Physical examination of pneumoscrotum typically includes crepitus of the perineal region and scrotal swelling and associated findings depending on the origin of the free air. However, pneumoscrotum in the setting of a scrotal wound, which allows air to pass freely outside the body, has not been previously documented in the literature. CASE REPORT A 72-year-old man who recently underwent a scrotal incision and drainage for recurrent epididymitis presented to a local emergency room with chief concerns of "whistling scrotum" and dyspnea. The chest CT revealed bilateral pneumothoraces, pneumomediastinum, and excessive subcutaneous emphysema throughout his abdomen, perineum, and scrotum. His scrotum had a dehiscent wound without any gross edema or air trapping contained within the scrotum. He received bilateral chest tubes and subcutaneous air drains with complete resolution of his pneumothoraces. The pneumoscrotum and associated subcutaneous emphysema of the perineum and thighs resolved after a prolonged period, and necessitated additional scrotal surgery. CONCLUSIONS Prompt evaluation for source control is necessary with pneumoscrotum, as the source likely requires immediate stabilization or surgical intervention. This case report describes a unique presentation of a common entity (pneumothorax) within pulmonology/critical care in a patient with an open scrotal wound from a recent scrotal procedure, which allowed the air to escape from his abdominal compartment, and resulted in his "scrotal whistling." It is unclear how the air passing through the scrotum affected the patient's presentation, such as allowing more air to build up in the subcutaneous tissues versus developing critical illness.

Neisseria Gonorrhoeae Spontaneous Bacterial Peritonitis.

We describe a case of gonococcal spontaneous bacterial peritonitis (SBP) in a 48-year-old sexually active female with alcoholic cirrhosis and chronic hepatitis B. She was admitted with fever, abdominal pain and distension without dysuria, dyspareunia, or vaginal discharge. On exam, she was icteric with features of sepsis and tense ascites. She underwent paracentesis. The ascitic fluid analysis revealed a neutrophil count of 1,050/µL, and culture grew Neisseria gonorrhoeae. Pelvic examination findings were negative for pelvic inflammatory disease; however, an endocervical swab was positive for N. gonorrhoeae by PCR. She was diagnosed with spontaneous bacterial peritonitis secondary to N. gonorrhoeae and was successfully treated with a seven-day course of IV ceftriaxone. N. gonorrhoeae spontaneous bacterial peritonitis is an extremely rare entity reported only twice despite the high prevalence of gonorrhoeae in the general population. We hypothesize that gonococcal SBP may be frequently undiagnosed since it responds to empiric antibiotics used to treat SBP. It is important for the clinician to be aware of gonococcus as a rare but potential pathogen in SBP. Future studies are needed to determine if routine gonococcal screening in SBP cases would be of clinical utility.

Reduction of central line-associated bloodstream infections in a large acute care hospital in Midwest United States following implementation of a comprehensive central line insertion and maintenance bundle.

BACKGROUND: Central line-associated bloodstream infection (CLABSI) is a preventable medical condition that results in increased patient morbidity and mortality. We describe the impact of various quality improvement interventions on the incidence of CLABSI in an 848-bed community teaching hospital from 1 January 2013 to 31 December 2017. AIM: To reduce CLABSI rates after implementation of a comprehensive central line insertion and maintenance bundle. METHODS: A comprehensive bundle of interventions was implemented incorporating the standard US Centers for Disease Control and Prevention bundle with additional measures such as root-cause analysis of all CLABSI cases, use of passive disinfection caps on vascular access ports, standardisation of weekly central venous catheter (CVC) site dressing changes, and use of antithrombotic and antimicrobial-coated CVCs with fewer lumens. A retrospective study evaluated CLABSI rates and time of CLABSI onset after CVC placement in both intensive care unit (ICU) and non-ICU settings. RESULTS: The annual number of CLABSI cases declined 68% (34 to 11 patients) from 2013 to 2017. There was a 30% decline in CVC days from years 2014 to 2017. Over the same period, CLABSI cases per 1000 CVC days decreased from 0.624 to 0.362: a 42% decline. CONCLUSION: Following the implementation of a comprehensive bundle of interventions for CVC insertion and maintenance, we found a reduction in rates of CLABSI.

A Risk-Stratified Peri-Operative Protocol for Reducing Surgical Site Infection after Cesarean Delivery.

Background: Surgical site infections (SSI) are multifaceted. Pre-operative, intra-operative, and post-operative factors influence the risk of developing an infection. Our objective was to evaluate the effectiveness of an infection risk-stratification checklist, utilizing known SSI risk factors, and a tailored surgical protocol for SSI prevention in women undergoing cesarean delivery. Patients and Methods: A prospective project to reduce SSI was conducted for women undergoing cesarean delivery on the resident staff service at a midwestern, urban tertiary care hospital. Patients were categorized according to an SSI risk-stratification checklist as high risk or low risk. The low-risk group received the local standard of care (single prophylactic dose of pre-operative intravenous antibiotics and a standard pressure dressing). In the high-risk group, prophylactic antibiotic agents were given pre-operatively and continued for the first 24 hours post-operatively. Additionally, patients at high risk received an absorbent dressing (Mepilex Ag®; Mölnlycke Health Care AB, Gothenburg, Sweden) that was applied in the operating room and worn for one week. Results: The overall rate of SSIs decreased from 6.1% (pre-study rate) to 1.4% after initiation of the protocol, a 77% reduction (p < 0.001). The low- and high-risk groups did not differ in infection rate (0% and 1.4%, respectively; p < 0.59). Both deep incisional and organ/space SSIs decreased after initiation of the protocol (91% and 62% decrease, respectively). Conclusion: Stratifying patients into high- and low-risk groups with tailored peri-operative management strategies reduced overall SSIs. The protocol incorporates known risk factors for SSI in a surgical procedure with high rates of SSI. This approach offers a structured method that can be adopted by other hospital systems for SSI prevention in patients undergoing cesarean delivery.

Nocardia spp. Pneumonia in a Solid Organ Recipient: Role of Linezolid.

We describe a rare infection with Nocardia spp. (N. pseudobrasiliensis species identification based on high-performance liquid chromatography analysis) in a 68-year-old renal transplant recipient. He presented with pneumonia complicated by hypoxic respiratory failure. He was allergic to sulphonamides. He was initially successfully treated with linezolid. However, he suffered severe sensory neuropathy after 4 months of therapy, necessitating linezolid cessation and completion of treatment with azithromycin. He had clinical and radiological resolution of his pneumonia and was disease free at subsequent follow-up 4 years later. This case highlights the need for alternative therapies for nocardiosis for patients that cannot be treated with sulphonamides due to allergies or/and infection with multidrug-resistant pathogens. It also illustrates the treatment limiting side effects of long-term therapy with linezolid.

Comparing interferon- gamma release assay with tuberculin skin test readings at 48-72 hours and 144-168 hours with use of 2 commercial reagents.

BACKGROUND: Despite widespread use, the tuberculin skin test (TST) has many limitations, including a requirement for a second visit between 48 and 72 hours. The goal of this study was to determine the reliability of a TST reading between 144 and 168 hours. METHODS: Tuberculin antigen was applied into both forearms (Aplisol in one arm and Tubersol in the other, from single lots of each product) by the Mantoux method. Blood samples were obtained for interferon- gamma release assay. Subjects were seen at 48-72 hours for the initial (day 2) TST reading and returned at 144-168 hours for a second (day 7) reading. RESULTS: A total of 116 subjects at increased risk for tuberculosis were studied; 25 (22%) had positive results at day 2 with Tubersol and 27 (23%) had positive results at day 2 with Aplisol. Overall agreement between Tubersol and Aplisol at day 2 was 93% (kappa = 0.80) and at day 7 was 94% (kappa = 0.76). Overall agreement between day 2 and day 7 was 89% for Tubersol and 86% for Aplisol. Discordant results between day 2 and day 7 occurred mostly in persons with a history of bacille Calmette-Guerin vaccination. CONCLUSIONS: Subjects who fail to present at 48-72 hours for TST reading may still have a reliable TST reading at up to 168 hours. Aplisol and Tubersol reagents produce comparable results when compared with the interferon- gamma release assay.

New Therapies for Hepatitis C Virus.

Hepatitis C virus (HCV), the major etiologic agent of "non-A, non-B hepatitis" was discovered 26 years ago. Even before its discovery, interferon-α (IFN) was already being used for treatment of this infection. The next two decades saw a series of incremental improvements of the IFN therapies by extending the duration of therapy, using IFN in combination with oral ribavirin, using pegylated IFN with ribavirin, and most recently adding oral compounds that inhibit the HCV replication (directly acting antivirals - DAAs) to that regimen. DAAs target multiple steps in the HCV life cycle and are now used in combination to treat HCV infection without the need of IFN. These IFN-free, oral DAAs regimens are highly efficacious, have minimal toxicity and are given for short duration. Approved DAAs can cure more then 90% of persons with chronic HCV infection, thereby reducing the risk of death from cirrhosis and hepatocellular carcinoma. However, these drugs are very expensive, and currently their exorbitant cost significantly restricts the access to this therapy for many HCV infected patients.

Cutaneous zygomycosis following attempted radial artery cannulation.

A 70-year-old man was seen in a hospital consultation for evaluation of cellulitis of the left arm. The patient had multiple medical problems, including advanced liver disease due to alcohol, diabetes mellitus, congestive heart failure, atrial fibrillation, chronic renal in sufficiency, and hypopituitarism requiring steroid replacement. Most recently, he was admitted to the intensive care unit, where he required intubation and mechanical ventilation support following respiratory failure secondary to pneumonia. At that time, an attempt was also made to place an arterial line in the left radial artery. The patient had multiple areas of ecchymosis on both arms. A large bulla was found on the lateral aspect of the left wrist several days after the attempted arterial line placement. Subsequently, the lesion drained serosanguineous fluid, and, during the next 2 days, it ulcerated with necrosis extending around the wrist and to the elbow. He was started on ampicillin/sulbactam and clindamycin for presumed necrotizing fasciitis. The surgical service performed a very limited debridement,which was partially limited by his coagulopathy from liver disease. The initial tissue culture was positive only for Enterococcus faecium. At the time of the consultation, his temperature was 95' F (35 degrees C), pulse 82 bpm, respirations 16 BPM, and blood pressure 101/56 mmHg. He was awake but not oriented or responsive. His cardiopulmonary exam was unremarkable. Abdominal exam disclosed ascites. His extremities were all grossly edematous with multiple ecchymoses. His left forearm had a circumferential area of ecchymosis and necrosis with macerated margins, sparing only the lateral ulnar epicondyle, and involving deeper structures of subcutaneous fat and muscle(Figures 1-2 showing evolution of the lesion in a period of 1 week). Small tissue clippings were taken from the edge of the lesion and placed on culture plates. By the next morning, the patient's tissue culture grew a mold, later identified as Rhizopus. Amphotericin B was initiated. Surgical intervention (wide debridement with potential conversion to amputation of the left arm) was considered to offer little benefit in view of the patient's multiple and severe comorbidities and his poor prognosis. Amphotericin B was then stopped; the patient died within a week from his multiple medical complications. The family refused an autopsy.

Acute limb ischemia due to Candida lusitaniae aortic valve endocarditis.

We present a case of a 35-year-old male with history of intravenous heroin use, who presented with acute limb ischemia and was found to have Candida lusitaniae endocarditis. After an urgent intervention to salvage the right lower extremity, successful outcome of his infection was achieved by a combined surgical and antifungal treatment.

Infection Related Glomerulonephritis Associated with Staphylococcus epidermidis in the Absence of Prosthetic Material.

We report a case of a 72-year-old diabetic male who developed infection-related glomerulonephritis (IRGN) in the setting of severe Staphylococcus epidermidis infection. He required renal replacement therapy for 6 weeks, but had full recovery of his kidney function with aggressive treatment of the infection. While this pathogen has been previously implicated as the cause of shunt nephritis, it is exceptionally rare to be associated with IRGN in the absence of a shunt or other prosthetic material.

Challenges in the management of infections due to carbapenem-resistant Enterobacteriaceae.

Carbapenem-resistant Enterobacteriaceae (CRE) infections are increasing and are associated with considerable morbidity and mortality. Members of the Emerging Infections Network treating CRE encountered difficulties in obtaining laboratory results and struggled with limited treatment options. In addition, many treated patients experienced an alarming degree of drug toxicity from CRE therapies.

The use of ivacaftor in an adult with severe lung disease due to cystic fibrosis (ΔF508/G551D).

We report on an adult with cystic fibrosis (ΔF508/G551D) with severe lung disease (forced expiratory volume (FEV1) in one second 24% predicted) who was admitted for a pulmonary exacerbation. He was managed with maximal medical therapy, but did not have significant improvement until after he was started on ivacaftor on hospital day 15. He subsequently had significant improvement in lung function with normalization of hypercarbia, oxygen saturation on room air, and increase in FEV1 to 36% predicted. Prior to use of ivacaftor he was being assessed for a lung transplant. However, after ivacaftor therapy for 6 months, he is no longer considering this treatment modality due to his improvement of lung function and functional status.