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Tuberculous lymphadenitis is one of the most common extrapulmonary manifestation of tuberculosis. Lymphadenitis due to Listeria monocytogenes is rarely described. We present a case of a 59-year-old woman from Mexico presented to the Emergency Department with a 2-week history of erythematous and painful swelling in the right retromandibular area. An ultrasound-guided bedside needle aspiration of the lump was performed by an infectious diseases specialist and a diagnosis of Listeria monocytogenes and tuberculous coinfection was done. To our knowledge this is the first case of tuberculous and Listeria-associated lymphadenitis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

BACKGROUND SARS-CoV-2 infection can persist in immunocompromised patients with hematological malignancies, despite antiviral treatment. This report is of a 67-year-old man with chronic lymphocytic leukemia (CLL), secondary hypogammaglobulinemia, and thrombocytopenia on maintenance therapy with ibrutinib, with persistent SARS-CoV-2 infection unresponsive to antiviral treatment, including remdesivir, nirmatrelvir/ritonavir (Paxlovid), and tixagevimab/cilgavimab (Evusheld). CASE REPORT The patient was admitted to our hospital 3 times. During his first hospitalization, he was treated with 5-day course of remdesivir and intravenous steroids; however, antigen and molecular nasopharyngeal swabs were persistently positive, and he was discharged home. Due to respiratory worsening, he was rehospitalized, and despite being treated initially with tixagevimab/cilgavimab, and subsequently with a remdesivir course of 5 days, SARS-CoV-2 tests remained persistently positive. During his third hospital stay, our patient was subjected to combined therapy with remdesivir and nirmatrelvir/ritonavir for 5 days, obtaining a significant reduction of viral load at both antigen and molecular testing. As an ultimate attempt to achieve a negative status before discharge, a 10-day course of combined remdesivir and nirmatrelvir/ritonavir was administered, with a temporary reduction of viral load, followed by a sudden increase immediately after the discontinuation of Paxlovid. Due to worsening hematological disease and bacterial over-infections, the patient gradually worsened until death. CONCLUSIONS This is an emblematic case of correlation between persistent SARS-CoV-2 infection and immunosuppression status in hematological hosts. In these patients, the viral load remains high, favoring the evolution of the virus, and the immunodeficiency makes it difficult to identify the appropriate therapeutic approach.

External ventricular drain-related cerebrospinal fluid infection represents a fearsome complication of neurosurgical interventions. Although vancomycin represents the standard of care for methicillin-resistant CoNS healthcare-associated ventriculitis, resistance phenomena have been described. We reported a case of a persistent external ventricular fluid drain infection after device removal by pandrug-resistant Staphylococcus epidermidis successfully treated with intravenous ceftaroline in combination with fosfomycin and vancomycin. No evidence regarding pandrug-resistant S. epidermidis therapy currently exists to our knowledge. In this case, the S. epidermidis phenotype emerged during the therapy course, possibly due to initial device retention, biofilm formation and the host immune impaired response. Despite being poorly studied in vivo, ceftaroline may be considered an option when other alternatives are unavailable, thanks to its described activity against CoNS in vitro. This case extends the experience with ceftaroline for central nervous system infections suggesting it could also be used in high antimicrobial resistance settings for immunocompromised people., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: Biofilm formation (BF) by fungal isolates may dramatically complicate infection. We determined the ability of Candida parapsilosis isolates from single fungaemia episodes to form biofilms and we analysed biofilm subgroups for antifungal susceptibility and pathogenic potential. We then correlated BF with clinical characteristics and outcomes of the episodes., Methods: BF was measured using the crystal violet biomass assay. Antifungal susceptibility of preformed biofilms was assessed, and virulence was studied using the Galleria mellonella model. A retrospective analysis of patients' clinical records was performed., Results: Of 190 patient-unique isolates, 84, 38 and 68 were identified as having high BF (HBF), moderate BF (MBF) or low BF (LBF), respectively. Among 30 randomly selected isolates, nine (eight HBF and one MBF), six (all HBF) and one (HBF) isolates had elevated sessile minimum inhibitory concentrations to fluconazole, anidulafungin or amphotericin B; all HBF and MBF isolates had elevated voriconazole sessile minimum inhibitory concentrations. G. mellonella killing rates of HBF isolates were significantly greater than MBF (or LBF) isolates (50% vs. 20%, 2 days from infection). By comparing HBF/MBF (106 patients) and LBF (84 patients) groups, we found that HBF/MBF patients had more central venous catheter-related fungaemias (62/106 (58.5%) vs. 29/84 (34.5%), p 0.001) and were more likely to die at 30 days from fungaemia onset (61/106 (57.5%) vs. 28/84 (33.3%), p 0.01). In the HBF/MBF group, azole antifungal therapy and central venous catheter removal were significantly associated with a higher and lower 30-day mortality rate, respectively., Conclusions: C. parapsilosis BF influences the clinical outcome in patients with fungaemia., (Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objectives: Infections caused by Klebsiella pneumoniae (Kp) carbapenemase (KPC)-producing strains of Kp have become a significant threat in recent years. To assess their outcomes and identify risk factors for 14 day mortality, we conducted a 4 year (2010-13) retrospective cohort study in five large Italian teaching hospitals., Methods: The cohort included 661 adults with bloodstream infections (BSIs; n = 447) or non-bacteraemic infections (lower respiratory tract, intra-abdominal structure, urinary tract or other sites) caused by a KPC-Kp isolate. All had received ≥48 h of therapy (empirical and/or non-empirical) with at least one drug to which the isolate was susceptible., Results: Most deaths occurred within 2 weeks of infection onset (14 day mortality: 225/661, 34.1%). Logistic regression analysis identified BSI (OR, 2.09; 95% CI, 1.34-3.29), presentation with septic shock (OR, 2.45; 95% CI, 1.47-4.08), inadequate empirical antimicrobial therapy (OR, 1.48; 95% CI, 1.01-2.18), chronic renal failure (OR, 2.27; 95% CI, 1.44-3.58), high APACHE III score (OR, 1.05; 95% CI, 1.04-1.07) and colistin-resistant isolates (OR, 2.18; 95% CI, 1.37-3.46) as independent predictors of 14 day mortality. Combination therapy with at least two drugs displaying in vitro activity against the isolate was associated with lower mortality (OR, 0.52; 95% CI, 0.35-0.77), in particular in patients with BSIs, lung infections or high APACHE III scores and/or septic shock at infection onset. Combinations that included meropenem were associated with significantly higher survival rates when the KPC-Kp isolate had a meropenem MIC of ≤8 mg/L., Conclusions: KPC-Kp infections are associated with high mortality. Treatment with two or more drugs displaying activity against the isolate improves survival, mainly in patients who are critically ill., (© The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Knowledge of carbapenem-resistant Klebsiella pneumoniae (CR-KP) colonization is important to prevent nosocomial spread but also to start prompt adequate antibiotic therapy in patients with suspicion of infection. However, few studies have examined the incidence and risk factors for CR-KP bloodstream infection (BSI) among rectal carriers. To identify risk factors for CR-KP BSI among carriers, we performed a multicentre prospective matched case-control study of all adult CR-KP rectal carriers hospitalized in five tertiary teaching hospitals in Italy over a 2-year period. Carriers who developed CR-KP BSI were compared with those who did not develop subsequent BSI. Overall, 143 CR-KP BSIs were compared with 572 controls without a documented infection during their hospitalization. Multivariate analysis revealed that admission to the Intensive Care Unit (ICU) (OR, 1.65; 95% CI, 1.05-2.59; p 0.03), abdominal invasive procedure (OR, 1.87; 95% CI, 1.16-3.04; p 0.01), chemotherapy/radiation therapy (OR, 3.07; 95% CI, 1.78-5.29; p <0.0001), and number of additional colonization sites (OR, 3.37 per site; 95% CI, 2.56-4.43; p <0.0001) were independent risk factors for CR-KP BSI development among CR-KP rectal carriers. A CR-KP BSI risk score ranging from 0 to 28 was developed based on these four independent variables. At a cut-off of ≥2 the model exhibited a sensitivity, specificity, positive predictive value and negative predictive value of 93%, 42%, 29% and 93%, respectively. Colonization at multiple sites with CR-KP was the strongest predictor of BSI development in our large cohort of CR-KP rectal carriers., (© 2014 The Authors Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases.)

Several methods to increase the sensitivity of JC virus (JCV) DNA detection in cerebrospinal fluid (CSF) for a noninvasive diagnosis of AIDS-related progressive multifocal leukoencephalopathy (PML) were investigated. When CSF collected at clinical presentation was tested, JCV DNA was detected in 8 of 19 patients with PML by standard PCR (sensitivity, 42%; 95% confidence interval [CI], 21 to 66%) and in 14 of 19 by nested PCR (sensitivity, 74% [95% CI, 49 to 90%]; P = 0.014 [McNemar's test]. For multiple serial CSF samples, standard PCR yielded JCV DNA for 11 of 19 PML patients (sensitivity, 58% [95% CI, 34 to 79%]) and nested PCR yielded JCV DNA for 17 of 19 patients (sensitivity, 90% [95% CI, 66 to 98%]; P = 0.014). The majority of the false-negative samples were found to contain PCR inhibitors. Standard PCR did not detect JCV DNA in CSF from any of the 83 AIDS patients with other diagnosis (100% specificity [95% CI, 95 to 100%]); JCV DNA was found in CSF from one control patient by nested PCR (99% specificity [95% CI, 93 to 100%]).

Objective: To investigate the efficacy and safety of three regimens for primary prophylaxis of Pneumocystis carinii pneumonia (PCP) and toxoplasmic encephalitis (TE) and to evaluate their effect on survival in patients with HIV infection., Design: Randomized, open label, prospective trial., Setting: A single Infectious Diseases Department in Italy., Patients: HIV-infected patients (n = 197) with a CD4 count < 200 x 10(6)/l and without previous PCP or TE., Interventions: Patients were randomly assigned to receive (1) aerosolized pentamidine (AP; 300 mg monthly), (2) cotrimoxazole (CTX; 160 mg trimethoprim and 800 mg sulfamethoxazole every other day), or (3) dapsone-pyrimethamine (DP; 100 mg weekly dapsone and 25 mg biweekly pyrimethamine)., Main Outcome Measures: PCP, TE, death, and drug-limiting toxicity. Considering difference in PCP occurrence the trial was interrupted on June 1992. Observation was prolonged until June 1994 for TE and survival., Results: Intention-to-treat analysis yielded PCP rates of 10.2 per 100 person-years in the AP, 2.0 in the CTX, and 32.1 in the DP group [adjusted relative risk of DP versus CTX: 17.5; 95% confidence interval (CI), 2.2-139.6; P = 0.007]. TE rates in patients with positive Toxoplasma serology were 25.6 per 100 person-years in the AP, 8.9 in the CTX and 9.4 in the DP group. In 'on treatment' analysis, no episode of TE developed in the DP group, and rates were 34.7 per 100 person-years in the AP and 2.5 in the CTX group (AP versus CTX: P = 0.01; AP versus DP: P = 0.004). The adjusted risk of mortality for the DP group was 2.8 times that of the CTX group in the first part of the study (95% CI, 1.1-7.3; P = 0.037), and 1.8 times (95% CI, 1.1-2.9; P = 0.02) in the prolonged follow-up. No significant difference in the occurrence of serious adverse reactions was observed between the three treatment groups., Conclusions: Intermittent CTX was more effective than low-dose DP and showed a slight but not significant advantage on AP for primary PCP prophylaxis. DP was associated with a shorter survival. Both CTX and DP resulted in a significant reduction in the risk of TE.

Technetium-99m (99mTc) labelled polyclonal human immunoglobulin (HIG) is a new agent for the localization of active inflammatory diseases. The results obtained with HIG in 29 AIDS patients referred for suspected lung infections are reported (Table I). The patients also underwent Gallium-67 citrate scanning (GS), chest radiography (Rx), high-resolution thin-layer computed tomography (HRCT) and broncho-alveolar lavage (BAL). The study population was classified as follows: 12 patients (Table II) were studied before treatment for suspected Pneumocystis carinii pneumonia (PCP), 7 patients (Table III) had known PCP and were studied during medical therapy, and 10 patients (Table IV) had lung infections other than PCP. In all PCP patients studied before treatment, positive agreement was observed between HIG, Rx and HRCT findings. In 4 patients with final clinical diagnosis of no lung conditions, both nuclear and radiologic imaging were negative. 99mTc-HIG results in the PCP patients studied during therapy were consistent with clinical and radiologic improvement; there was disagreement with 67Ga findings in one case (no. 9). In lung infections other than PCP, HIG studies were often negative (always negative in mycobacteriosis), while they were positive in 3 pyogenic abscesses. In conclusion, as for PCP and abscesses, the results obtained with 99mTc-HIG are usually in agreement with GS findings, while HIG scans seem to be negative in mycobacterial infections. Moreover, HIG scintigraphy seems to be suitable for the evaluation of treatment results in PCP (this subject deserves further research). To assess respiratory impairment a semiquantitative index (ISQ) of 99mTc-HIG lung uptake is suggested, which showed a significant linear correlation with arterial pO2.

DNA amplification by the polymerase chain reaction (PCR) is a promising method for the detection of Pneumocystis carinii in immunosuppressed patients. The sensitivity and specificity of the PCR technique has been assessed in comparison with the immunofluorescence method (IF) on bronchoalveolar lavage fluid (BALF). Results correlated in 43 (78.8%) of 52 cases studied. P. carinii PCR gave positive results with BALF from all 32 patients found to have P. carinii pneumonia (PCP); IF gave positive results with 26 of them. PCR was more sensitive and as specific as IF. However, at the present time, we do not believe that it is clinically useful for detection of P. carinii in BALF samples. P. carinii DNA amplification by PCR should be reserved for testing IF-negative BALF samples from patients judged clinically to have PCP.

Fifty-five episodes of Pneumocystis carinii pneumonia (PCP) in AIDS patients were evaluated to assess clinical and laboratory risk factors predicting the probability of surviving the acute episode of PCP and the long-term survival after PCP. Age > 45 yrs, PaO2 < 50 mmHg, AaPO2 > 50 mmHg, and LDH > 800 IU/L correlated strongly with early mortality; patients who needed mechanical ventilation had a significantly lower PaO2 and serum albumin, and higher AaPO2 and LDH compared to the patients who did not. Neither age nor PaO2, AaPO2, LDH, albumin, days from onset, time for recovery, CD4+ cell count correlated with long-term survival of AIDS patients with PCP. Informations obtained at initial presentation of PCP may predict early outcome and influence therapeutic approach, improving chances for survival.

In vitro production of TNF-alpha by alveolar macrophages was investigated in 15 AIDS patients with acute interstitial pneumonia and in 4 patients with asymptomatic HIV infection (anti-HIV+) and was compared to that observed in 6 patients with chronic pulmonary disease and in 5 normal controls (undergoing a fiberoptic bronchoscopy for suspected lung malignancy), all 11 HIV negative. Our results show that unstimulated alveolar macrophages of AIDS and anti-HIV+ patients released much more TNF-alpha than subjects with chronic obstructive pulmonary disease or healthy controls did: this overproduction may play a role in the pathogenesis of lung damage infection and particularly in AIDS patients.

We retrospectively examined 39 patients with AIDS and central nervous system toxoplasmosis in order to determine the efficacy and safety of two combinations: pyrimethamine-sulfadiazine and pyrimethamine-clindamycin. The results showed a response rate of 79% for the sulfadiazine association and a high failure rate in the clindamycin group. Side effects with sulfadiazine were slightly more frequent, but with desensitization protocols discontinuation was kept down. The combination of pyrimethamine and sulfadiazine, associated, when necessary, with desensitization schedules, was confirmed to be first choice therapy for cerebral toxoplasmosis in AIDS patients. The role of alternative regimens needs further evaluation.

The ability of Pneumocystis carinii to induce tumor necrosis factor (TNF)-alpha release by monocytes/macrophages from immunocompetent humans was investigated. Monocytes and monocyte-derived macrophages from healthy individuals produced an increased amount of TNF-alpha when exposed to P. carinii cysts obtained from rats with steroid-induced pneumocystosis. The cysts induced increased TNF-alpha production in a dose-dependent manner; baseline TNF-alpha production was restored after addition of an anti-P. carinii hyperimmune serum. Kinetics experiments showed that the secretion of TNF-alpha occurs early and reaches a maximal peak after 8 h. Since TNF-alpha is directly lethal to P. carinii in vitro, it is suggested that the production of this cytokine in response to the cysts may be one of the mechanisms for the control of this parasitic infection.

We report the results of a study held between 1986 and 1988 on a population constituted by 493 subjects (425 of Mozambican nationality) all living in the camp organized for the building of the dam in Corumana (Sabiè district, Maputo). We found five subjects, all of them from Mozambique, seropositive for HIV-1 antibodies (ELISA and WB) with a prevalence of 1.2%. Four of the positive samples came from female subjects (1.7% of 239 females tested); one positive sample came from a male subject (0.5% of 186 tested).

Scintigraphy with 99mTc labelled human polyclonal immunoglobulin was performed in 16 patients with ascertained or suspected AIDS-related infections. 99mTc-HIG lung scanning was compared, in 11 patients, with 67Ga scintigraphy, chest X-ray and high resolution lung CT. 67Ga and 99mTc-HIG were concordantly positive in five cases of BAL-ascertained Pneumocystis carinii pneumonia (PCP), while one of them was Rx and CT negative. X-ray, 67Ga and 99mTc were concordantly negative in 5 cases. 99mTc-HIG yielded negative results in two cases of Mycobacterium infection, both of which were 67Ga and Rx positive: Mycobacterium avium in diffuse lung involvement and Mycobacterium TBC in excavated infiltrate. 99mTc-HIG was also positive in other 3 AIDS patients: 1 case of intestinal cryptosporidiosis, 1 pulmonary abscess (Staphylococcus and Candida), and 1 sacral abscess; it was negative in 1 case of Kaposi sarcoma (also 201Tl negative). In conclusion, 99mTc-HIG scintigraphy in AIDS patients is feasible, and offers some practical advantages (continuous availability, fast response time, etc.). The initial results seem similar to those of 67Ga in lung scanning (and perhaps more specific for PCP).

Mycological, cultural and/or serological studies were performed on 98 patients hospitalized in the Department of Infectious Diseases of the Catholic University in Rome with diagnoses of acquired immune deficiency syndrome (AIDS) or AIDS-related complex (ARC) diseases. The incidence of mycoses was evaluated by retrospectively analyzing the results of mycological examinations and comparing them with clinical manifestations. The presence of concomitant bacterial, viral and parasitic infections was also examined. For epidemiological purposes, the study was extended to include the biotyping of all yeasts isolated from patients hospitalized between September 1988 and February 1989 in the same Department. Antimycotic susceptibility was also determined for the first yeast isolate obtained from each of these patients. Oral candidiasis (50 cases) caused by Candida albicans was the most frequent mycosis, followed by esophageal candidiasis (13 cases) and cryptococcosis (6 cases). Four out of the 6 cryptococcosis patients had meningeal involvement. Systemic candidiasis (2 cases) and aspergillosis (1 case) were less common. Biotyping of yeasts isolated between September 1988 and February 1989 with the killer system revealed type 377 to be the most common among the C. albicans isolates. It represented 70% of all the yeasts isolated.

The ability of Pneumocystis carinii to induce TNF-alpha release by macrophages from adult healthy humans was investigated. Monocytes and monocytes derived macrophages produced an high amount of TNF-alpha when exposed to P. carinii cysts obtained from rats with steroid induced pneumocystosis. TNF-alpha release was P. carinii specific as shown by the inhibition exerted by the anti-P. carinii hyperimmune serum and it was not mediated by putative traces of endotoxin.