Ganciclovir-resistant cytomegalovirus infections among lung transplant recipients are associated with poor outcomes despite treatment with foscarnet-containing regimens.

Ganciclovir-resistant cytomegalovirus (CMV) infections are reported infrequently among lung transplant recipients receiving extended valganciclovir prophylaxis. We performed a single-center, retrospective review of ganciclovir-resistant CMV infections in a program that employed valganciclovir prophylaxis for ≥6 months after lung transplant. CMV infections were diagnosed in 28% (170/607) of patients. UL97 mutations were detected in 9.4% (16/170) of CMV-infected patients at a median of 8.5 months posttransplant (range, 5 to 21) and despite prophylaxis for a median of 7 months (range, 4 to 21). UL97 mutations were canonical; 25% (4/16) of strains carried concurrent UL54 mutations. Ganciclovir-resistant CMV was more likely with breakthrough infections (75% [12/16] versus 19% [30/154]; P = 0.00001) and donor positive/recipient negative (D+/R-) serostatus (75% versus 45% [69/154]; P = 0.03). The median whole-blood CMV load was 4.13 log10 copies/cm(3) (range, 2.54 to 5.53), and 93% (14/15) of patients had low-moderate immune responses (Cylex Immunoknow). Antiviral therapy was successful, failed, or eradicated viremia followed by relapse in 12% (2/16), 31% (5/16), and 56% (9/16) of patients, respectively. Eighty-seven percent (14/16) of patients were treated with foscarnet-containing regimens; toxicity developed in 78% (11/14) of these. Median viral load half-life and time to viremia eradication among foscarnet-treated patients were 2.6 and 23 days, respectively, and did not correlate with protection from relapse. Sixty-nine percent (11/16) of patients developed CMV pneumonitis, and 25% (4/16) died of it. Serum viral load was independently associated with death among foscarnet-treated patients (P = 0.04). In conclusion, ganciclovir-resistant CMV infections remained a major cause of morbidity and mortality following lung transplantation. Foscarnet-based regimens often eradicated viremia rapidly but were ineffective in the long term and limited by toxicity.

Novel approaches in the treatment of Hansen's disease (Leprosy): a case series of multidrug therapy of monthly rifampin, moxifloxacin, and minocycline (RMM) in the United States.

The World Health Organization (WHO) recommends multidrug therapy (MDT) for the treatment of paucibacillary and multibacillary forms of leprosy, also known as Hansen's disease (HD). MDT combinations of dapsone, rifampin, and clofazimine have reduced the prevalence of the disease but are not without adverse effects impacting regimen adherence. Hence, an urgent need exists to consider alternative MDT regimens with an improved safety profile that promotes treatment adherence. Herein, we described a case series of 10 patients with HD (nine patients with multibacillary leprosy and one with pure neural leprosy) treated with monthly rifampin, moxifloxacin, and minocycline (RMM). The United States National Hansen's Disease Program (NHDP) diagnosed and treated patients across US institutions. All patients received a regimen of 12-24 months of RMM. We reviewed the clinical outcomes, adherence, rate of completion, and adverse events of patients treated with monthly RMM from January 2019 to August 2022. Nine patients had multibacillary leprosy, with some having type-2 reactions. One patient had pure neural leprosy with a reversal reaction. In this case series, we identified that all patients completed the RMM regimen without treatment interruptions. None of the patients experienced any skin hyperpigmentation or any significant side effects. All patients tolerated the monthly RMM regimen with rapid improvement of skin lesions and without logistic hurdles. Based on previous clinical evidence and the results of this case series, the NHDP and other programs should consider the RMM regimen as first-line therapy.

Advances in the Development of Microbicides for the Prevention of HIV Infection.

Microbicides are products that can be applied to vaginal or rectal mucosa with the intent of preventing, or at least significantly reducing, the transmission of sexually transmitted infections, including HIV-1. The past 2 or 3 years of microbicide research have generated several disappointments. Large, phase 2B/3 studies failed to demonstrate product efficacy, were stopped prematurely for futility, and in the worst-case scenario possibly demonstrated microbicide-induced harm. The most recently completed efficacy study (HPTN-035) did not reach statistical significance, but did show that use of PRO-2000 was associated with a 30% reduction in HIV acquisition. Current research focuses on much more potent targeted therapy, including reverse transcriptase inhibitors and CCR5 antagonists. Ongoing challenges include optimizing the identification of safety signals in phase 1/2 studies, defining a rationale for advancing products into efficacy studies, and identifying populations with adequate HIV seroincidence rates for these studies.

Peptostreptococcus infective endocarditis and bacteremia. Analysis of cases at a tertiary medical center and review of the literature.

Peptostreptococcus infective endocarditis is rare but associated with high morbidity. We report two cases and evaluate all positive blood cultures for Peptostreptococcus at our institution, followed by a review of the literature. This organism causes a subacute presentation and cardiac valve pathology is a risk factor. Penicillin remains the treatment of choice.

Candida rugosa: a distinctive emerging cause of candidaemia. A case report and review of the literature.

Candida rugosa is a rare cause of candidaemia, but important to recognize because of frequent azole-resistance and its association with catheters and total parenteral nutrition. Recommended therapy is an echinocandin or amphotericin, and catheter discontinuation. Fluconazole might be substituted based on susceptibility testing and a clinical response to initial therapy.

Enterococcus faecalis Septicemia and Vertebral Osteomyelitis after Transrectal Ultrasound Guided Biopsy of the Prostate.

Transrectal ultrasound guided prostate biopsy (TRUS) has rarely been associated with disseminated infection, yet the occurrence appears to be increasing. Resistance to fluoroquinolones, the most commonly used prophylaxis, is one of the likely causes, with Escherichia coli being the most commonly reported cause of these infections. Herein we present what is, to our knowledge, the first case of Enterococcus faecalis septicemia and vertebral osteomyelitis after TRUS. Previously reported cases of this condition are referenced also.

Experience with linezolid for the treatment of nocardiosis in organ transplant recipients.

OBJECTIVES: Combination therapy with amikacin is recommended for treatment of nocardiosis in severely ill solid organ transplant recipients (SOT), but its use is complicated by nephrotoxicity. Linezolid has shown promise as an alternative in the empiric therapy of nocardiosis, but little is known about its effectiveness and safety in this setting. We describe the experience with linezolid for nocardiosis in SOT. METHODS: Retrospective review of cases of nocardiosis in SOT at a large center from 2006 to 2012. RESULTS: Nineteen cases were identified, 15/19 in lung transplant recipients. Median creatinine clearance at diagnosis was 56 ml/min. Eighteen patients were treated: 17/18 (94%) received trimethoprim/sulfamethoxazole and 15/18 (83%) received linezolid. Median duration of linezolid treatment was 21 days and it was discontinued in 10/15 (67%) due to side effects. Thrombocytopenia and anemia occurred in 14/15 (93%) and 9/15 (60%) of patients on linezolid, respectively, and were not different from patients not on linezolid. Cure was observed in 16/19 (84%), 33% of deaths were related to nocardiosis. CONCLUSIONS: Linezolid was acceptable as initial empiric therapy for nocardiosis. Myelosuppression was a limiting factor, but not exclusive to patients on linezolid and could have been aggravated by concomitant use of other myelosuppressive drugs.

Staphylococcus aureus infections in the early period after lung transplantation: epidemiology, risk factors, and outcomes.

BACKGROUND: Staphylococcus aureus infections among lung transplant recipients are poorly studied. METHODS: We conducted a 5-year retrospective study of the epidemiology, clinical manifestations, risk factors, and outcomes of patients infected with S aureus within the first 90 days after lung transplantation. RESULTS: An S aureus infection developed in 109 of 596 lung transplant (18%) recipients. Methicillin-susceptible S aureus (MSSA; 62%) was more common than methicillin-resistant S aureus (MRSA; 38%); however, the proportion of infections caused by MRSA increased over time. Pneumonia (48%) was the most common infection, followed by tracheobronchitis (26%), bacteremia (12%), intrathoracic infections (7%), and skin/soft tissue infections (7%). Risk factors included mechanical ventilation for > 5 days and isolation of S aureus from recipients' sterility cultures. Patients with MRSA cultured from the nares or respiratory tract at the time of transplant were at an increased risk for MRSA infection (p < 0.0001 and p = 0.02, respectively). Infected patients required longer hospital and intensive care unit stays (p < 0.0001 for both), but the 30- and 90-day mortality rates from the onset of infection were only 7% and 12%, respectively. However, infected patients had higher rates of acute and chronic rejection at 1 (p = 0.048) and 3 years (p = 0.002), and higher rates of mortality at 1 (p = 0.058) and 3 years (p = 0.009). CONCLUSIONS: S aureus infections within the first 90 days of lung transplant were associated with low short-term mortality but increased long-term rates of mortality and acute and chronic rejection. Future studies are needed to explore the utility of S aureus eradication strategies in reducing disease burden and improving outcomes.