Association of Vancomycin AUC/MIC and Trough Concentration With Early Clinical Response in Enterococcus or Coagulase-Negative Staphylococcus Infection: A Prospective Study.

This study was condcuted to examine the association of area under the curve (AUC)/minimum inhibitory concentration (MIC) and trough concentration (Ctrough) of vancomycin with treatment outcome and nephrotoxicity in infections caused by Enterococcus spp. and coagulase-negative Staphylococci (CoNS). Peak and trough concentrations were used to calculate AUC in 89 patients receiving vancomycin for infections with Enterococcus spp. (n = 65) or CoNS (n = 24). Correlations between Ctrough, AUC/MIC, early clinical response (ECR), and nephrotoxicity were assessed and cutoff values were determined. Sixty-three (70.8%) patients showed improvement in ECR and 10 (11.2%) experienced nephrotoxicity. Enterococcus spp. infections displayed correlations between AUC/MIC and ECR for AUC0-24 h/MIC (r2 = 0.27, P ≤ .05) and AUC24-48 h/MIC (r2 = 0.28, P ≤ .05), but not for Ctrough (r2 = 0.21, P > .05). There were no correlations between Ctrough (r2 = 0.26, P > .05), AUC0-24 h/MIC (r2 = -0.12, P > .05), AUC24-48 h/MIC (r2 = 0.01, P > .05) and ECR for CoNS. In the CoNS group, a moderate correlation was found between ECR and Ctrough at a cutoff value of 6.9 µg/mL. In addition, nephrotoxicity is also moderately associated with AUC0-24 h and AUC24-48 h at 505.7 and 667.1 µg•h/mL, respectively. A strong correlation between nephrotoxicity and Ctrough was observed when the cutoff value was 18.9 µg/mL. AUC/MIC during the first 48 h was a determinant of vancomycin efficacy in Enterococcus infections but not for CoNS. Ctrough was not correlated with clinical outcome. Nephrotoxicity could be predicted using Ctrough and AUC for infections with both pathogens.

A two-arm analysis of the immune response to heterologous boosting of inactivated SARS-CoV-2 vaccines.

Several vaccine programs were introduced during the COVID-19 pandemic, which included inactivated virus, DNA viral vectors and mRNA vaccines. Booster programs are recommended, especially for those in high-risk groups. However, many of these booster programs involve heterologous vaccines. This study enrolled volunteers who first received two full-dose CoronaVac vaccinations before receiving heterologous boosters with DNA- and/or mRNA-vaccines for an additional 2 doses (n = 40) or an additional 3 doses (n = 16). Our results showed no difference in side effects, neutralizing antibodies, or T-cell responses for any of the heterologous vaccination programs. However, the neutralizing capacity and IFN-γ responses against the Omicron variant in volunteers who received 4 or 5 doses were improved. Polarization of peripheral memory T cells after stimulation in all booster groups with Omicron peptide showed an increased trend of naïve and central memory phenotypes of both CD4+ and CD8+ T cells, suggesting that exposure to Omicron antigens will drive T cells into a lymphoid resident T cell phenotype. Our data support a continuous vaccination program to maximize the effectiveness of immunity, especially in people at high risk. Furthermore, the number of boosting doses is important for maintaining immunity.

The CREPE Score: A Predictive Tool for Third-Generation Cephalosporin-Resistant Enterobacterales Pneumonia in Community Settings.

Purpose: To evaluate risk factors and develop a prediction score for community-acquired pneumonia caused by third-generation cephalosporin-resistant Enterobacterales (3GCR EB-CAP). Patients and Methods: A retrospective study was conducted by reviewing the medical records of patients hospitalized with community-acquired pneumonia caused by Enterobacterales (EB-CAP) between January 2015 and August 2021 at Srinagarind Hospital, Khon Kaen University, Thailand. Logistic regression was used to analyze clinical parameters associated with 3GCR EB-CAP. The coefficients of significant parameters were simplified to the nearest whole number for a prediction score, called the CREPE (third-generation Cephalosporin Resistant Enterobacterales community-acquired Pneumonia Evaluation). Results: A total of 245 patients with microbiologically confirmed EB-CAP (100 in the 3GCR EB group) were analyzed. Independent risk factors for 3GCR EB-CAP included in the CREPE score were (1) recent hospitalization within the past month (1 point), (2) multidrug-resistant EB colonization (1 point), and (3) recent intravenous antibiotic use (2 points for within the past month or 1.5 points for between one and twelve months). The CREPE score had an area under the receiver operating characteristic curve (ROC) of 0.88 (95% CI 0.84-0.93). Using a cut-off point of 1.75, the score had a sensitivity and specificity of 73.5% and 84.6%, respectively. Conclusion: In areas with high prevalence of EB-CAP, the CREPE score can assist clinicians in selecting appropriate empirical therapy and reducing overuse of broad-spectrum antibiotics.

Efficacy of Oral Ivermectin as Empirical Prophylaxis for Strongyloidiasis in Patients Treated with High-Dose Corticosteroids: A Retrospective Cohort Study.

People living in areas endemic for strongyloidiasis are at risk of latent Strongyloides stercoralis infection. Corticosteroid therapy is a well-established risk factor for life-threatening hyperinfection syndrome and disseminated disease owing to suppression of the immune system. There are limited data available on the efficacy and cost of providing oral ivermectin prophylaxis to all patients receiving high-dose corticosteroids for strongyloidiasis in endemic areas. We thus conducted this retrospective cohort study at Khon Kaen University's Srinagarind Hospital from 2015 to 2019. Inclusion criteria were as follows: age ≥ 18 years, having received ≥ 0.5 mg/kg/day of prednisolone or equivalent for at least 14 days, and hospitalization during the study period. A total of 250 patients were included in the study: 125 in the empirical prophylaxis group (prescribed ivermectin even if fecal examination results were negative or nonexistent) and the remaining patients in the definite therapy group (prescribed ivermectin only if S. stercoralis was detected by fecal examination). The prevalence of strongyloidiasis at enrollment estimated by fecal examination was 5.5%. Ivermectin was given to 125 patients (100%) in the prophylaxis group compared with 12 (9.6%) in the definite therapy group (P value < 0.001). During the 12-month follow-up period, S. stercoralis was detected in three patients, two in the prophylaxis group and one in the definite therapy group (P value = 1.000). No cases of hyperinfection syndrome or disseminated disease were found. The empirical prophylaxis strategy had a significantly higher cost than the definite therapy strategy (563 versus 254, P value < 0.001) and did not demonstrate superior efficacy in strongyloidiasis prevention.

Transmission sources and severe rat lung worm diseases in travelers: a scoping review.

BACKGROUND: Rat lung worm disease (RLWD) has several clinical forms including eosinophilic meningitis (EOM) and two severe forms, eosinophilic meningoencephalitis (EOME) and eosinophilic radiculomyelitis (EORM). It remains unclear whether transmission sources are associated with severe forms of RLWD. This study aimed to evaluate if transmission factors are related to the severity of RLWD among travelers by using a scoping review of case reports. METHODS: This was a review using five databases to retrieve case reports and case series of travelers with RLWD. Clinical data and transmission sources of reported cases diagnosed as RLWD were retrieved. The outcome of the study was occurrence of severe forms of RLWD defined as EOME, EORM, and combined EOME/EORM. RESULTS: We retrieved 1,326 articles from five databases and 31 articles were included in the analysis. There were 84 cases eligible from 15 countries. Four cases were excluded. Seventy cases were in EOM group and 10 cases had EOME or EORM. Compared with the EOM group, the EOME, EORM, and combination EOME/EORM group had similar age, sex, and risk factors of consumptions of apple snails, shrimp and prawn, and salad/vegetables. The EOME group had higher proportion of consumption of African snails than the EOM group (60% vs 13.8%). However, only one study reported the consumption of African snails and the heterogeneity between studies and the small sample size impeded direct comparisons between groups. CONCLUSIONS: RLWD in travelers can be found in most continents and mostly get infected from endemic countries of RLWD. Further studies are required to evaluate the association between transmission vectors and severity of RLWD.

Immunogenicity of a fractional or full third dose of AZD1222 vaccine or BNT162b2 messenger RNA vaccine after two doses of CoronaVac vaccines against the Delta and Omicron variants.

OBJECTIVES: The study aimed to compare the immunogenicity and safety of fractional (half) third doses of heterologous COVID-19 vaccines (AZD1222 or BNT162b2) to full doses after the two-dose CoronaVac and when boosting after three different extended intervals. METHODS: At 60-<90, 90-<120, or 120-180 days intervals after the two-dose CoronaVac, participants were randomized to full-dose or half-dose AZD1222 or BNT162b2, followed up at day 28, 60, and 90. Vaccination-induced immune responses to Ancestral, Delta, and Omicron BA.1 strains were evaluated by antispike, pseudovirus, and microneutralization and T cell assays. Descriptive statistics and noninferiority cut-offs were reported as geometric mean concentration or titer and concentration or titer ratios comparing baseline to day 28 and day 90 and different intervals. RESULTS: No safety concerns were detected. All assays and intervals showed noninferior immunogenicity between full doses and half doses. However, full-dose vaccines and/or longer 120-180-day intervals substantially improved the immunogenicity (measured by antispike or measured by pseudotyped virus neutralizing titers 50; P <0.001). Seroconversion rates were over 90% against the SARS-CoV-2 strains by all assays. Immunogenicity waned more quickly with half doses than full doses but remained high against the Ancestral or Delta strains. Against Omicron, the day 28 immunogenicity increased with longer intervals than shorter intervals for full-dose vaccines. CONCLUSION: Immune responses after day 28 when boosting at longer intervals after the two-dose CoronaVac was optimal. Half doses met the noninferiority criteria compared with the full dose by all the immune assays assessed.

Virological outcomes and metabolic effects after switching from ritonavir-boosted protease inhibitors to a dolutegravir-based regimen in virologically suppressed patients living with HIV.

BACKGROUND: A ritonavir-boosted protease inhibitor (PI)-based antiretroviral therapy (ART) regimen can cause abnormal lipid levels and increased incidence of cardiovascular disease. Switching to a dolutegravir (DTG)-based regimen has been shown to improve blood lipid levels, but data in the Thai population are limited. METHOD: A prospective cohort study was conducted at Srinagarind Hospital between April 28, 2021, and April 30, 2022. Patients were eligible if they (1) were over 18 years of age, 2) had received a ritonavir-boosted PI-based regimen for at least three months, and 3) had documented plasma HIV RNA levels below 50 copies/mL within six months before the enrollment. All eligible patients included in the study switched from a ritonavir-boosted PI-based ART regimen to a DTG-based regimen. The primary outcome was changes in low-density lipoprotein cholesterol (LDL-C) levels from baseline to week 24. RESULTS: Forty-six eligible patients were enrolled, 71.7% of whom were male, with a mean age of 49.4 years. Mean body weight was 62.7 kg and body mass index (BMI) was 22.86 kg/m2. The majority of patients had been on a regimen of boosted atazanavir (ATV/r; 60.9%), followed by boosted lopinavir (LPV/r; 37.0%). Six patients were withdrawn from the study. At week 24 after switching to DTG, LDL-C was significantly lower than at baseline, with a difference of -15.1 mg/dL (95% confidence interval [CI; -23.3 to -6.8]; p-value < 0.001), as were total cholesterol and triglycerides, with differences of -22.1 mg/dL (95% CI [-33.3 to -10.8]; p-value <0.001) and -67.7 mg/dL, (95% CI [-88.3 to -47.0]; p-value 0.001), respectively. There were no significant changes in body weight (0.51 kg; 95% CI [-0.37 to 1.38]; p-value 0.251) or BMI (0.17 kg/m2; 95% CI [-0.14 to 0.48]; p-value 0.284) from baseline to week 24. In addition, 39 of 40 patients (97.5%) maintained virological suppression (HIV RNA <50 copies/mL), with only one patient (2.5%) developing virological failure. Three grade 3 adverse events were observed. CONCLUSION: Switching from a boosted PI-based ART regimen to a DTG-based regimen in people living with HIV/AIDS who had attained prior virological suppression resulted in a significant reduction in total cholesterol, LDL-C, and triglyceride levels, but did not increase the patient's body weight at 24 weeks of follow-up. Furthermore, the DTG-based regimen was also highly effective in maintaining virological suppression. TRIAL REGISTRATION: Thai Clinical Trials Registry, TCTR20210625004.

Phenotypic and functional changes of T cell subsets after CoronaVac vaccination.

BACKGROUND: The pandemic coronavirus disease 2019 (COVID-19) is a major global public health concern and several protective vaccines, or preventive/therapeutic approaches have been developed. Sinovac-CoronaVac, an inactivated whole virus vaccine, can protect against severe COVID-19 disease and hospitalization, but less is known whether it elicits long-term T cell responses and provides prolonged protection. METHODS: This is a longitudinal surveillance study of SARS-CoV-2 receptor binding domain (RBD)-specific IgG levels, neutralizing antibody levels (NAb), T cell subsets and activation, and memory B cells of 335 participants who received two doses of CoronaVac. SARS-CoV-2 RBD-specific IgG levels were measured by enzyme-linked immunosorbent assay (ELISA), while NAb were measured against two strains of SARS-CoV-2, the Wuhan and Delta variants. Activated T cells and subsets were identified by flow cytometry. Memory B and T cells were evaluated by enzyme-linked immune absorbent spot (ELISpot). FINDINGS: Two doses of CoronaVac elicited serum anti-RBD antibody response, elevated B cells with NAb capacity and CD4+ T cell-, but not CD8+ T cell-responses. Among the CD4+ T cells, CoronaVac activated mainly Th2 (CD4+ T) cells. Serum antibody levels significantly declined three months after the second dose. INTERPRETATION: CoronaVac mainly activated B cells but T cells, especially Th1 cells, were poorly activated. Activated T cells were mainly Th2 biased, demonstrating development of effector B cells but not long-lasting memory plasma cells. Taken together, these results suggest that protection with CoronaVac is short-lived and that a third booster dose of vaccine may improve protection.

The comparative accuracy of pooled vs. individual blood culture sampling methods for diagnosis of catheter-related bloodstream infection.

BACKGROUND: Catheter-related bloodstream infection (CRBSI) is associated with increased morbidity, mortality, and cost of treatment in critically ill patients. A differential time to positivity (DTP) of 120 min or more between blood cultures obtained through the catheter vs. peripheral vein is an indicator of CRBSI with high sensitivity and specificity. However, it is no clear whether pooled sampling would be as efficient as individual sampling in order to reduce costs, contamination, or anemia. METHODS: This was a prospective diagnostic study conducted at the medical ICU and semi-ICU of Khon Kaen University's Srinagarind Hospital in Thailand from May 2020 to November 2021. Fifty patients with triple-lumen central venous catheters (CVCs) who were clinically suspected of CRBSI were enrolled. 15 mL of blood was drawn through each catheter lumen, 10 mL of which was inoculated into three blood culture bottles, and the remaining 5 mL was pooled into a single bottle. Sensitivity, specificity, accuracy, and time to positivity of the pooled blood cultures were calculated using individual blood cultures as a reference. RESULTS: Of the 50 patients enrolled, 14 (28%) were diagnosed with CRBSI, 57.9% of whom were infected with gram-negative bacteria as the causative pathogen (57.9%). Extensively drug-resistant (XDR) Klebsiella pneumoniae was the most common organism. Sensitivity and specificity of the pooled blood sampling method were 69.23% (95% CI [0.44-0.94]) and 97.3% (95% CI [0.92-1.02]), respectively. The area under the ROC curve (AUC) was 0.83 (95% CI [0.68-0.99]). A paired T-Test to compare time to positivity of the pooled blood bottle and the first positive culture from the individual bottles indicated statistical significance (14.9 and 12.4 h, respectively). The mean difference was 2.5 [0.9-4.1] h, with a 95% CI and a p-value of 0.006. CONCLUSION: Pooled blood sampling results in a lower sensitivity and longer time to positivity for CRBSI diagnosis in patients with triple-lumen CVCs than individual lumen sampling. Trial registration Retrospectively registered at Thai Clinical Trials Registry. The study was reviewed and approved on 08/03/2022. TCTR identification number is TCTR20220308002.

In vitro susceptibility of Burkholderia pseudomallei isolates from Thai patients to ceftolozane/tazobactam and ceftazidime/avibactam.

OBJECTIVES: Treatment options are limited for melioidosis patients who develop nosocomial infections due to extensively drug-resistant (XDR) Gram-negative bacilli. Ceftolozane/tazobactam (C/T) and ceftazidime/avibactam (CZA), which have activity against XDR Gram-negative bacteria, are two potential options. Data regarding the susceptibility of Burkholderia pseudomallei to these agents are limited, especially from Thailand, which is an endemic area for melioidosis. METHODS: A total of 28 B. pseudomallei isolates from melioidosis patients in northeast Thailand were tested for susceptibility to C/T and CZA by Etest and the disk diffusion method. Minimum inhibitory concentrations (MICs) for other antibiotics commonly used in melioidosis, including trimethoprim/sulfamethoxazole (SXT), ceftazidime (CAZ), imipenem (IPM) and meropenem, were also determined. RESULTS: The MIC of C/T was very low for all isolates, ranging from 0.75 µg/mL to 1.0 µg/mL. For CZA, wide inhibitory zones ranging from 34-35 mm and MICs at 0.5 µg/mL were found. All isolates were also susceptible to SXT, CAZ and IPM based on Clinical and Laboratory Standards Institute (CLSI) breakpoints. CONCLUSION: C/T and CZA exhibited excellent in vitro activity against B. pseudomallei. Further studies are required to prove efficacy in human subjects.

Insertion of a Clinical Pathway Pop-Up Window into a Computer-Based Prescription System: A Method to Promote Antibiotic Stewardship in Upper Respiratory Tract Infection.

Outpatient antibiotics are most frequently prescribed for upper respiratory tract infection (URI); however, most such prescriptions are inappropriate. We aimed to determine the effect of an electronic clinical pathway on the rates of overall and rational prescription of antibiotics in patients with URI. A pilot quasi-experimental study was conducted in a university hospital and two of its nearby primary care units (PCU) in northeast Thailand from June to September 2020. Clinical pathway pop-up windows were inserted into the hospital's computer-based prescription system. Care providers were required to check the appropriate boxes before they were able to prescribe amoxicillin or co-amoxiclav. We examined a total of 675 visits to the outpatient department due to URI at three points in time: pre-intervention, immediately post-intervention, and 6 weeks post-intervention. Patients in the latter group tended to be younger and visits were more likely to be general practitioner-related and to the student PCU than in the other two groups. In addition, the rate of antibiotic prescription was significantly lower at 6 weeks after intervention than at either of the other time periods (32.0% vs 53.8% pre-intervention and 46.2% immediately post-intervention; p < 0.001), and the proportion of rational antibiotic prescriptions increased significantly after implementation. Antibiotic prescription rates were lower at the community primary care unit and higher when the physician was a resident or a family doctor. The deployment of an electronic clinical pathway reduced the rate of unnecessary antibiotic prescriptions. The effect was greater at 6 weeks post-implementation. However, discrepancy of patients' baseline characteristics may have skewed the findings.

Presentations of chronic cavitary pulmonary histoplasmosis mimic infected cystic bronchiectasis in an immunocompetent host: A case report.

BACKGROUND: Chronic cavitary pulmonary disease and laryngeal involvement are unusual manifestations of Histoplasmosis capsulatum infection, particularly in patients who are not immunocompromised. The presence of fibro-cavitary lesions has been reported as a radiologic presentation of chronic histoplasmosis in patients with pre-existing lung disease. However, there have been few reports of extensive basal predominant cavitary lesions that mimic cystic-bronchiectasis. CASE PRESENTATION: A 65-year-old previously healthy Thai male presented with productive cough, hoarseness, low-grade fever, and weight loss for 6 months. There was no history of significant exposure to Histoplasmosis capsulatum. Tests for HIV and anti-IFN- γ antibody were negative. Chest CT revealed multifocal thick wall cavities, which were distributed in a peri-bronchial pattern, and some areas of consolidation in both basal lungs. Laryngoscopy revealed an ulcerative lesion of the false vocal cords. Histopathological study of false vocal cords and lung tissue showed granulomatous inflammation with mixed inflammatory cell infiltration and aggregation of histiocytes containing round intracytoplasmic organisms. GMS-staining was positive, but negative mucicarmine-staining was negative. A real-time PCR assay of the lung tissue was positive for Histoplasmosis capsulatum. The final diagnosis was chronic cavitary pulmonary histoplasmosis with laryngeal involvement. CONCLUSION: Chronic cavitary pulmonary histoplasmosis is rare, as is laryngeal involvement. However, there have been such cases in endemic areas, even in immunocompetent patients. Chronic histoplasmosis should be considered in patients who present with the extensive basal predominant cavitary-pulmonary lesions that mimic cystic bronchiectasis.

Case Report: Angiostrongylus cantonesis Myelitis in Thailand.

A 67-year-old man presented with headache, middle back pain that radiated to both legs, and paresthesia in the right leg for 1 day. He had eaten raw shrimp 1 week previously. Over the next week after admission, he developed urinary retention and weakness in both legs. The numbness in his right leg expanded to below the umbilicus. Magnetic resonance imaging of the spinal cord showed myelopathy with minimal cord swelling at T9 to the conus medullaris and a hemorrhagic lesion from T10 to T11. A complete blood count on day 28 after the onset of symptoms revealed leukocytosis without eosinophilia and no white blood cells in his cerebrospinal fluid. Results of an immunochromatographic test kit were positive for Angiostrongylus cantonesis but negative for Gnathostoma spinigerum. After a 4-week course of albendazole combined with a tapering dose of dexamethasone, he achieved nearly complete recovery.

Differences in Duration and Degree of Cytomegalovirus DNAemia Observed With Two Standardized Quantitative Nucleic Acid Tests and Implications for Clinical Care.

Cytomegalovirus (CMV) viral loads overall were 0.29 log IU/mL higher with cobas CMV for use on the cobas 6800/8800 System (cobas CMV) compared with Cobas AmpliPrep/Cobas TaqMan CMV Test (CAP/CTM CMV). Cytomegalovirus DNAemia was detected 11.5 days earlier by cobas CMV, whereas clearance was delayed by 12.8 days. Cytomegalovirus remained detectable by cobas CMV in 44.2% of patients at the time of viral clearance as determined by CAP/CTM CMV. Undetectable viral load by cobas CMV at end of treatment was associated with reduced risk for retreatment (odds ratio, 0.26; 95% confidence interval, 0.04-0.99; P = .05). The use of different quantitative cytomegalovirus nucleic acid tests may affect direct patient care as a result of significant differences in reporting the degree of CMV DNAemia and the time to first detection and clearance of CMV DNAemia.

Clinical Correlation of Cytomegalovirus Infection With CMV-specific CD8+ T-cell Immune Competence Score and Lymphocyte Subsets in Solid Organ Transplant Recipients.

BACKGROUND: Control of cytomegalovirus (CMV) infection after solid organ transplantation (SOT) requires a functional immune system. We assessed the association between quantitation and function of CMV-specific CD8+ T cells and CMV infection in SOT recipients. METHODS: During a 10-year period, selected kidney, heart, lung, pancreas, liver, and composite tissue recipients were tested for CMV-specific CD8+ T cells immune competence (CMV-CD8+), as measured by enumeration, interferon-gamma production, and CD107a/b degranulation. Quantitative and functional data were used to assemble T-cell immune competence (TIC) score. CMV infection was diagnosed by polymerase chain reaction in blood and other samples or histopathology. RESULTS: Of 130 patients tested, 59 had CMV infection or disease. The median onset to CMV infection was 10.5 months (interquartile range [IQR], 5.5-18.7). Gastrointestinal disease (28.8%), pneumonia (20.3%), and CMV syndrome (17%) were most common presentation. An impaired nonspecific or CMV-CD8+ TIC score was associated with tissue-invasive disease (hazard risk, 2.84, 95% confidence interval, 1.03-11.81; P = 0.04). Patients with impaired CMV-CD8+ TIC score had longer viremia duration (42.4 days vs 18.8 d; P < 0.001). Patients with impaired nonspecific or CMV-CD8+ TIC score had higher risk of relapse (68.8% vs 27.9%; hazard risk, 2.56; 95% confidence interval, 1.09-5.89; P = 0.03). Patients with CMV infection or disease had lower median absolute lymphocyte count (380 [IQR, 240-540] vs 940 [IQR, 551-1210] cells/mm; P < 0.0001) and CD4+ T cell count (29 cells/mm [IQR, 1.3-116.0] vs 325.5 cells/mm [IQR, 151.5-589.8]; P < 0.0001). CONCLUSIONS: Nonspecific and CMV-specific CD8+ T-cell function correlated with the course of CMV after SOT, and measuring these has the potential to assist in its clinical management.

Absolute Lymphocyte Count Thresholds: A Simple, Readily Available Tool to Predict the Risk of Cytomegalovirus Infection After Transplantation.

This study of 64 solid organ and hematopoietic stem cell transplant recipients found that peripheral blood absolute lymphocyte count of <610 and <830/µL, respectively, correlated with cytomegalovirus infection. In an era when sophisticated measures of CMV-specific T cells are emerging, we emphasize the utility of the inexpensive and readily-available absolute lymphocyte count.

New Developments in the Management of Cytomegalovirus Infection After Transplantation.

Cytomegalovirus (CMV) continues to be one of the most important pathogens that universally affect solid organ and allogeneic hematopoietic stem cell transplant recipients. Lack of effective CMV-specific immunity is the common factor that predisposes to the risk of CMV reactivation and clinical disease after transplantation. Antiviral drugs are the cornerstone for prevention and treatment of CMV infection and disease. Over the years, the CMV DNA polymerase inhibitor, ganciclovir (and valganciclovir), have served as the backbone for management, while foscarnet and cidofovir are reserved for the management of CMV infection that is refractory or resistant to ganciclovir treatment. In this review, we highlight the role of the newly approved drug, letermovir, a viral terminase inhibitor, for CMV prevention after allogeneic hematopoietic stem cell transplantation. Advances in immunologic monitoring may allow for an individualized approach to management of CMV after transplantation. Specifically, the potential role of CMV-specific T-cell measurements in guiding the need for the treatment of asymptomatic CMV infection and the duration of treatment of CMV disease is discussed. The role of adoptive immunotherapy, using ex vivo-generated CMV-specific T cells, is highlighted. This article provides a review of novel drugs, tests, and strategies in optimizing our current approaches to prevention and treatment of CMV in transplant recipients.