Pseudomonas aeruginosa bloodstream infections in children and adolescents: risk factors associated with carbapenem resistance and mortality.

BACKGROUND: Pseudomonas aeruginosa bloodstream infections (PA-BSIs) are a serious disease and a therapeutic challenge due to increasing resistance to carbapenems. Our objectives were to describe the prevalence and risk factors associated with carbapenem resistance (CR) and mortality in children with PA-BSI. METHODS: A retrospective, multi-centre study was carried out, including patients aged <20 years with PA-BSI in four tertiary hospitals in Madrid (Spain) during 2010-2020. Risk factors for CR PA-BSIs and 30-day mortality were evaluated in a multi-variable logistic regression model. RESULTS: In total, 151 patients with PA-BSI were included, with a median age of 29 months (interquartile range: 3.5-87.1). Forty-five (29.8%) cases were CR, 9.9% multi-drug resistant and 6.6% extensively drug resistant. The prevalence of CR remained stable throughout the study period, with 26.7% (12/45) of CR mediated by VIM-type carbapenemase. Patients with BSIs produced by CR-PA were more likely to receive inappropriate empiric treatment (53.3% vs 5.7%, P<0.001) and to have been previously colonized by CR-PA (8.9% vs 0%, P=0.002) than BSIs caused by carbapenem-susceptible P. aeruginosa. CR was associated with carbapenem treatment in the previous month (adjusted odds ratio (aOR) 11.15) and solid organ transplantation (aOR 7.64). The 30-day mortality was 23.2%, which was associated with mechanical ventilation (aOR 4.24), sepsis (aOR 5.72), inappropriate empiric antibiotic therapy (aOR 5.86), and source control as a protective factor (aOR 0.16). CONCLUSION: This study shows a concerning prevalence of CR in children with PA-BSIs, leading to high mortality. Inappropriate empiric treatment and sepsis were associated with mortality. The high prevalence of CR with an increased risk of inappropriate empiric treatment should be closely monitored.

Antibiotic resistance in bloodstream isolates from high-complexity paediatric units in Madrid, Spain: 2013-2021.

BACKGROUND: Antimicrobial resistance (AMR) has become a significant challenge in high-complexity healthcare settings. AIM: To evaluate the prevalence of AMR in bloodstream isolates from high-complexity paediatric units in Spain over a nine-year period. METHODS: A retrospective observational multicentre study was conducted in three tertiary hospitals, analysing bloodstream isolates from patients aged <18 years admitted to the paediatric intensive care, neonatology, and oncology-haematology units between 2013 and 2021. Demographics, antimicrobial susceptibility, and resistance mechanisms were analysed in two periods (2013-2017 and 2017-2021). FINDINGS: In all, 1255 isolates were included. AMR was more prevalent in older patients and those admitted to the oncology-haematology unit. Multidrug resistance was observed in 9.9% of Gram-negative bacteria (GNB); 20.0% of P. aeruginosa vs 8.6% of Entero-bacterales (P < 0.001), with an increase in Enterobacterales from 6.2% to 11.0% between the first and the second period (P = 0.021). Difficult-to-treat resistance was observed in 2.7% of GNB; 7.4% of P. aeruginosa vs 1.6% of Enterobacterales (P < 0.001), with an increasing trend in Enterobacterales from 0.8% to 2.5% (P = 0.076). Carbapenem resistance among Enterobacterales increased from 3.5% to 7.2% (P = 0.029), with 3.3% producing carbapenemases (67.9% VIM). Meticillin resistance was observed in 11.0% of S. aureus and vancomycin resistance in 1.4% of Enterococcus spp., with both rates remaining stable throughout the study period. CONCLUSION: This study reveals a high prevalence of AMR in high-complexity paediatric units. Enterobacterales showed a concerning increasing trend in resistant strains, with higher rates among older patients and those admitted to oncology-haematology units.

Achromobacter xylosoxidans bacteremia: clinical and microbiological features in a 10-year case series.

OBJECTIVE: The treatment of Achromobacter xylosoxidans bacteremia is challenged by antimicrobial resistance and the paucity of data. We aimed at offering a contemporary description of this uncommon entity. METHODS: Retrospective case series of 13 episodes of A. xylosoxidans bacteremia diagnosed over a 10-year period (November 2007 to May 2017) in our tertiary care center. RESULTS: Solid organ cancer and heart failure were the most common comorbidities (4/13 [30.7%]). All but one episodes were hospital-acquired. Most patients had received previous antibiotic therapy (7/13 [53.8%]) and had a central venous catheter in place (6/13 [46.1%]). Primary and intravascular catheter were the most common sources (4/13 [30.7%] each). Meropenem was the agent with best in vitro activity (92.3% [12/13] of susceptible isolates). All-cause 30-day mortality (overall 23.1%) was higher in patients with primary bacteremia (50.0% vs. 11.1%; P-value=0.203) and prior chemotherapy (66.7% vs. 10.0%; P-value=0.108). CONCLUSIONS: Bacteremia due to A. xylosoxidans constitutes a serious infection among immunocompromised hosts. Carbapenem-based therapy may be appropriate in most cases.

Effect of respiratory Achromobacter spp. infection on pulmonary function in patients with cystic fibrosis.

PURPOSE: Cystic fibrosis (CF) patients are susceptible to infection with Achromobacter spp., although its clinical significance remains controversial. The aim of this study was to investigate the clinical impact of infection with Achromobacter spp. in CF patients. METHODS: CF outpatients with multiple sputum cultures and follow-up lung function tests were assigned to the case group (infected with Achromobacter spp.) or the control group (never infected with Achromobacter spp.) according to the isolation of Achromobacter spp. The Achromobacter spp. group included two subgroups, taking into consideration whether the isolation of Achromobacter spp. was intermittent or chronic. Baseline lung function tests and longitudinal behaviour were examined in relation to Achromobacter spp. status. RESULTS: A total of 190 CF patients were treated from January 2003 to December 2015 in the CF unit and 21 (11 %) had at least one positive culture for Achromobacter spp. Of these, 11/21 (52.4 %) patients were chronically infected with Achromobacter spp. An analysis of changes during follow-up showed the annual rate of FEV1 decline: -2.3±1.6 % in the Achromobacter spp. group compared to -1.1±0.9 % (P=0.02) in the control group. The chronically infected group also had a significantly greater decline in FEV1 compared to the control group (-2.9±1.9 vs -1.1±0.9; P=0.04). The mean number of annual pulmonary exacerbations during the study period was significantly higher in the case group (1.9±0.9 vs 1.1±0.8; P=0.03). CONCLUSIONS: The Achromobacter spp. status in CF shows a trend towards more severe airflow obstruction and an association with accelerated decline in lung function parameters.

Comparison of the clinical course of Clostridium difficile infection in glutamate dehydrogenase-positive toxin-negative patients diagnosed by PCR to those with a positive toxin test.

OBJECTIVES: To evaluate the potential role of PCR-based assays in the over-diagnosis of Clostridium difficile infection (CDI) by using a validated diagnostic algorithm in daily clinical practice. METHODS: We performed a retrospective cohort study evaluating all C. difficile-positive stool samples identified at our institution during a 12-month period, to compare outcomes and recurrence rates between patients with a positive enzyme immunoassay (EIA) for both glutamate dehydrogenase (GDH) and toxin A/B ('toxin-positive group'), with those with GDH-positive, toxin-negative samples in whom the diagnosis was made by a positive PCR-based assay ('toxin-/PCR+ group'). Medical records were reviewed by two independent investigators blinded to the mode of diagnosis. RESULTS: We analysed 231 first CDI episodes (106 (45.8 %) in the 'toxin-positive group' and 125 (54.1%) in the 'toxin-/PCR+ group'). Both groups had similar baseline characteristics. Patients in the 'toxin-positive group' presented more frequently with a severe/severe complicated form than those in the 'toxin-/PCR+ group' (36 (33.9%) versus 24 (19.2%); p 0.011) and had more recurrences (27 (25.5%) versus 9 (7.2%); p 0.001). Diagnosis of CDI based on a GDH/toxin-positive EIA independently predicted severe/severe-complicated course (adjusted OR 2.11; 95% CI 1.06-4.22; p 0.033) and recurrence (adjusted OR 3.79; 95% CI 1.65-8.69; p 0.002). There were no differences in all-cause mortality (12.3% versus 12.0%; p 0.95) or CDI-attributable mortality (4.7% versus 4.8%; p 0.93). CONCLUSIONS: Toxin-positive patients were more likely to have severe-complicated forms of CDI and recurrences. Nevertheless, CDI-related complications may still occasionally occur among toxin-negative patients diagnosed by PCR, which stresses the need for individualized clinical evaluation.

Pathogen-related factors affecting outcome of catheter-related bacteremia due to methicillin-susceptible Staphylococcus aureus in a Spanish multicenter study.

Even with appropriate clinical management, complicated methicillin-susceptible Staphylococcus aureus (MSSA) catheter-related bacteremia (CRB) is frequent. We investigated the influence of molecular characteristics of MSSA strains on the risk of complicated bacteremia (CB) in MSSA-CRB. A multicenter prospective study was conducted in Spain between 2011 and 2014 on MSSA-CRB. Optimized protocol-guided clinical management was required. CB included endocarditis, septic thrombophlebitis, persistent bacteremia and/or end-organ hematogenous spread. Molecular typing, agr functionality and DNA microarray analysis of virulence factors were performed in all MSSA isolates. Out of 83 MSSA-CRB episodes included, 26 (31.3%) developed CB. MSSA isolates belonged to 16 clonal complexes (CCs), with CC30 (32.5%), CC5 (15.7%) and CC45 (13.3) being the most common. Comparison between MSSA isolates in episodes with or without CB revealed no differences regarding agr type and functionality. However, our results showed that CC15 and the presence of genes like cna, chp and cap8 were associated with the development of CB. The multivariate analysis highlighted that the presence of cna (Hazard ratio 2.9; 95% CI 1.14-7.6) was associated with the development of CB. Our results suggest that particular CCs and specific genes may influence the outcome of MSSA-CRB.

Titania hollow spheres modified with tungstophosphoric acid with enhanced visible light absorption for the photodegradation of 4-chlorophenol.

Titania hollow spheres were synthesized using silica nanospheres as the template. The core was removed using NaOH solution. They were subsequently impregnated with tungstophosphoric acid (TPA) solutions and annealed at two different temperatures (100 and 500 °C). These materials were characterized by several physicochemical techniques (XRD, BET, SEM, DRS, FT-IR, FT-Raman and 31P MAS-NMR). The 31P MAS-NMR and FT-IR characterization showed that the main species present in the samples was the [PW12O40]3- anion, which was partially transformed into the [P2W21O71]6- anion during the synthesis and drying step. 31P MAS-NMR, and FT-Raman characterization revealed the evidence of a strong interaction between the Keggin anion of TPA and TiO2 surfaces, possibly due to the formation of surface heteropolyacid-TiO2 complexes. The DRS results showed that the absorption threshold onset continuously shifted to the visible region with increased TPA concentration and calcination at 500 °C. The enhanced visible light absorption could be related to the formation of a surface complex TPA Keggin anion-TiO2. The catalytic activity of the materials in the photodegradation of 4-chlorophenol under UV and visible light irradiation increased when the TPA content and the calcination temperature of the samples were raised.

Progressive increase of resistance in Enterobacteriaceae urinary isolates from kidney transplant recipients over the past decade: narrowing of the therapeutic options.

BACKGROUND: Antibiotic resistance is an emerging phenomenon in kidney transplantation (KT). METHODS: We compared species distribution and antimicrobial susceptibility patterns in 1052 isolates from urine cultures obtained in 2 different cohorts of kidney transplant recipients in a single center (Cohort A: 189 patients undergoing KT between January 2002 and December 2004 [336 isolates]; Cohort B: 115 patients undergoing KT between January 2011 and December 2013 [716 isolates]). RESULTS: Asymptomatic bacteriuria accounted for most of the isolates (86.9% in Cohort A and 92.3% in Cohort B). Klebsiella pneumoniae (9.5% vs. 15.6%), Pseudomonas aeruginosa (1.8% vs. 7.9%), and Enterobacter cloacae (0.6% vs. 3.1%) were significantly more common in Cohort B. The isolation of K. pneumoniae in Cohort B was associated with the occurrence of acute pyelonephritis (9.8% of all K. pneumoniae isolates vs. 2.8% of the remaining uropathogens; P = 0.001). Non-susceptibility rates among Enterobacteriaceae in Cohort B were higher for every class of antibiotics (P ≤ 0.003) with the exception of fosfomycin. Compared to Cohort A, significant increases were seen in isolates from Cohort B for multidrug-resistant (MDR) (43.9% vs. 67.8%, respectively; P = 0.001), extended-spectrum beta-lactamase (ESBL)-producing (6.6% vs. 26.1%; P = 0.001), and carbapenemase-producing Enterobacteriaceae strains (0.0% vs. 5.0%; P = 0.001). Such differences were mostly attributable to K. pneumoniae (as 54.5% and 13.4% of isolates in Cohort B were ESBL-producing and carbapenemase-producing, respectively). MDR isolates were responsible for 69.1% of episodes of symptomatic urinary tract infection in Cohort B. CONCLUSION: The increase in resistance rates among Enterobacteriaceae uropathogens is significant and may have an effect on KT programs.

Should Asymptomatic Bacteriuria Be Systematically Treated in Kidney Transplant Recipients? Results From a Randomized Controlled Trial.

The indication for antimicrobial treatment of asymptomatic bacteriuria (AB) after kidney transplantation (KT) remains controversial. Between January 2011 and December 2013, 112 KT recipients that developed one episode or more of AB beyond the second month after transplantation were included in this open-label trial. Participants were randomized (1:1 ratio) to the treatment group (systematic antimicrobial therapy for all episodes of AB occurring ≤24 mo after transplantation [53 patients]) or control group (no antimicrobial therapy [59 patients]). Systematic screening for AB was performed similarly in both groups. The primary outcome was the occurrence of acute pyelonephritis at 24-mo follow-up. Secondary outcomes included lower urinary tract infection, acute rejection, Clostridium difficile infection, colonization or infection by multidrug-resistant bacteria, graft function and all-cause mortality. There were no differences in the primary outcome in the intention-to-treat population (7.5% [4 of 53] in the treatment group vs. 8.4% [5 of 59] in the control group; odds ratio [OR] 0.88, 95% confidence interval [CI] 0.22-3.47) or the per-protocol population (3.8% [1 of 26] in the treatment group vs. 8.0% [4 of 50] in the control group; OR 0.46, 95% CI 0.05-4.34). Moreover, we found no differences in any of the secondary outcomes. In conclusion, systematic screening and treatment of AB beyond the second month after transplantation provided no apparent benefit among KT recipients (NCT02373085).

Risk factors for metastatic osteoarticular infections after a long follow-up of patients with Staphylococcus aureus bacteraemia.

We aimed to identify risk factors associated with the development of haematogenous metastatic osteoarticular infection (MOI) after an episode of Staphylococcus aureus bacteraemia (SAB). We followed 198 patients with SAB during a median of 68.9 months. Nine (4.54%) developed an MOI (median: 6.77 months) after SAB. Factors associated with MOI were the presence of joint prosthesis (hazard ratio 17.56; 95% CI 4.48-68.85) and osteoporosis (hazard ratio 8.46; 95% CI 1.9-37.57). MOI is a common complication after SAB and is related to high morbidity and mortality. Patients with previous osteoarticular disease are at the greatest risk of developing this complication.

Relación de los niveles plasmáticos de proteína C reactiva con infección y edema en la cirugía de los terceros molares retenidos / Relation between CRP levels as indicator of postoperative infection and edema after third molar impacted surgery

La proteína C reactiva (CRP) por sus siglas en inglés) es una proteína de fase aguda que se utiliza para el seguimiento de enfermedades inflamatorias tales como artritis reumatoidea, lupus eritematoso o vasculitis y procesos infecciosos tales como sepsis y septicemia; así como también, para evaluar la eficacia de las drogas antiinflamatorias y antimicrobianas indicadas en el tratamiento de estas patologías. Igualmente se ha asociado a daño tisular en diversas especialidades quirúrgicas. El objetivo de este estudio fue relacionar los niveles plasmáticos de CRP con la infección y el edema posterior a la cirugía de los terceros molares. A tal efecto se evaluaron 60 pacientes, distribuidos en 3 grupos A, B y C bajo antibioticoterapia profiláctica con Clindamicina (A: dosis única de 600 mg, B: 300 mg c/6h por 5 días y C: Placebo) y terapia analgésica y antiinflamatoria (Ibuprofeno 400mg c/6h por 3 días). A quienes se tomaron muestras de sangre antes y a las 72 horas de la odontectomía de los terceros molares y fotografías digitales para calcular el área de inflamación. No se demostró la relación de los niveles de CRP con infección ya que ningún paciente presentó proceso infeccioso pero si se demostró la relación cualitativa (sensibilidad) de CRP y cuantitativa mediante correlación de Spearman (p<0,05) ya que mientras mayor fue el área de la inflamación, mayores fueron los niveles plasmáticos de CRP

The C reactive protein (CRP) is an unspecific acute phase reaction used for the follow-up of such inflammatory diseases such as rheumatoid arthritis, lupus, or vasculitis and such infectious processes like sepsis; as well as also, to evaluate the efficiency of the anti-inflammatory and antimicrobial drugs indicated in the treatment of this pathologies. Equally it has associated to tissue damage in diverse surgical specialties. The aim of this study was to evaluate the relation between CRP levels as indicator of postoperative infection and edema after third molar surgery. We evaluated 60 patients distributed in three groups A, B and C under antibiotic prophylaxis with Clindamycin (A: single dosis 600 mgs, B: 300 mgs each 6/h by 5 days and C: placebo) and analgesic and anti-inflammatory therapy with Ibuprofen 400 mg. each 6/h by 3 days. Who were taken blood samples to measure the CRP before and 72 hours after surgery and digital photographs to calculate the edema area. We did not demonstrated relation between CRP and infection because no one patient was infected in any group but we demonstrated (By Searman (p<0,05) the value of CRP as indicator of edema in the third molar surgery

[Which is the best empirical treatment in patients with urethritis?]. / ¿Qué tratamiento empírico es el más adecuado en pacientes con uretritis?

OBJECTIVE: To know the best empirical treatment of urethritis in patients at the City Center of Madrid. METHODS: 2.021 urethral exudates were analyzed in men between January 2003-December 2007. In addition to the traditional cultures, it was determined the presence of Chlamydia trachomatis, Ureaplasma urealyticum, Mycoplasma hominis, Trichomonas vaginalis and Herpes simplex. The susceptibility of N.gonorrhoeae and Haemophilus spp was performed by disk diffusion method and U. urealyticum by Mycoplasma IST. RESULTS: The percentage of positive samples was: 30.6%. The most frequently isolated microorganisms were: U. urealyticum 9.9%, N. gonorrhoeae 7.4%, C. trachomatis 5.1% and Haemophilus spp 3.8%. The resistance of N. gonorrhoeae in the first period was: penicillin 11.8%, tetracycline 5.9%, ciprofloxacin 8.8% and presence of betalactamase 11.8%. In the second period: penicillin 9.7%, amoxicillin/clavulanic acid 1.4%, tetracycline 8.3%, ciprofloxacin 23.6% and presence of betalactamase 10.5%. Resistance to ciprofloxacin in non-MSM (men having sex with men) was 20% and in MSM 56.2%. Resistance of Haemophilus spp in the first period was: 38.2% ampicillin, amoxicillin/clavulanic acid 8.8%, clarithromycin 35.3%, cotrimoxazole 64.7%, cefuroxime 5.9%, ciprofloxacin 8.8%, tetracycline 12.1% and presence of betalactamase 26.5%. In the second period:presence of betalactamase 41.9%, ampicillin 53.1%, amoxicillin/clavulanic acid 9.4%, cefuroxime 9.4%, clarithromycin 18.7%, tetracycline 34.4%, ciprofloxacin 15.6%, and cotrimoxazole 68.7%. Resistance of U. urealyticum was: ciprofloxacin 80.7%, ofloxacin 32.4%, erythromycin 17.5%, azithromycin 9.6%, tetracycline 3.5% and doxycycline 0.8%. CONCLUSIONS: N. gonorrhoeae showed a level of resistance to tetracycline and ciprofloxacin higher in the second period, being significant for ciprofloxacin. Quinolone resistance was higher in MSM. Haemophilus spp showed a level of resistance to ampicillin, ciprofloxacin and tetracycline higher in the second period, being significant for tetracycline. U.urealyticum showed high level of resistance to ciprofloxacin (80.7%)and ofloxacin (32.4%) and low level of resistance to doxycycline (0.8%) and tetracycline (3.5%).

[Diagnosis of urethritis in men. A 3-year review]. / Diagnóstico microbiológico en varones. Revisión de 3 años.

OBJECTIVES: The aim of this study is to know the prevalence and tendency of microorganisms producing urethritis, in men, in the City Centre of Madrid. METHODS: Cross-sectional study. The urethral samples of 1.248 men were analyzed, for 3 years. The samples were studied for: GRAM stain, when secretion exists; culture in habitual plates; detection of C. trachomatis, U. urealyticum and M. hominis, when there was suspicious, study of T. vaginalis and when suspicious injuries exist, study of virus Herpes simplex. RESULTS: The percentage of positive samples was 22.60%. The isolated microorganisms were: U. urealyticum 7.61%, N. gonorrhoeae 6.33%, C. trachomatis 4.81%, M. hominis 0.24%, H. parainfluenzae 1.76%, H. influenzae 1.12%, Candida spp 0.48%, S. pyogenes 0.16% and Herpes virus simplex (2) 0.08%. Two or more microorganisms were isolated in 1.68%. The percentage of positive samples in 2003 was 17.41% and N. gonorrhoeae the most frequent microorganism (6.22%). In 2004 was 25.57% and the most frequent U. urealyticum (10.18%). In 2005 the 24.50% of the samples were positive and U. urealyticum the most frequent (7.92%). The 79.41% of N. gonorrhoeae were susceptible to all antibiotics tested. It is not found resistance to ceftriaxone, claritromicine and amoxicilline/clavulanic acid. The 11.76% were betalactamase- producing. The 26.47% of Haemophilus spp. were betalactamase- producing and all strains were susceptible to cefotaxime. CONCLUSIONS: The isolated microorganisms most frequently were: U. urealyticum, N. gonorrhoeae and C. trachomatis. There is an increase of 7% of prevalence between the years 2003 and 2005. Ceftriaxone, claritromicine and amoxicilline/clavulanic acid were susceptible to all the strains studied and cefotaxime to all Haemophilus spp.

Susceptibility to chronic infection with Toxoplasma gondii does not correlate with susceptibility to acute infection in mice.

Resistance against acute and chronic infection with Taxoplasma gondii in BALB/c and CBA/Ca mice was compared. Intraperitoneal inoculation of either 20, 40, or 80 cysts of the ME49 strain resulted in mortality rates in BALB/c mice of 12% (2 of 17), 50% (6 of 12), and 75% (9 of 12), respectively, within 3 weeks after infection (acute stage). There was no mortality in the CBA/Ca mice for any of the doses. In marked contrast, CBA/Ca mice were highly sensitive to chronic infection with developing toxoplasmic encephalitis; they began dying 2 months after infection with 10 cysts of the ME49 strain, and mortality reached 53% (16 of 30) by the sixth month postinfection. No mortality (0 of 20) was observed in the chronically infected BALB/c mice. CBA/Ca mice had markedly more cysts in their brains than BALB/c mice in the chronic stage. Severe inflammatory changes were observed only in the brains of CBA/Ca mice. Interestingly, in the acute stage (the first 3 weeks), numbers of cysts in the brains were significantly greater in CBA/Ca than BALB/c mice, whereas only BALB/c mice showed mortality in that time period. No inflammatory changes were observed in brains of BALB/c mice during the acute stage of the infection. Thus, resistance against chronic infection appears to be regulated by a mechanism(s) that is different from those conferring resistance against acute infection. There was no difference in gamma interferon levels in sera between CBA/Ca and BALB/c mice during the acute stage. However, during the chronic stage, only BALB/c mice had detectable levels of gamma interferon in their sera.

A gene(s) within the H-2D region determines the development of toxoplasmic encephalitis in mice.

Studies were performed in a murine model to determine if there is genetic control of the development of toxoplasmic encephalitis. Ten weeks after infection with the ME49 strain of Toxoplasma gondii, mice with the H-2b haplotype (C57BL/6, C57BL/10) and H-2k haplotype (C3H/He, CBA/J) developed remarkable inflammatory changes in their brains, whereas mice with the H-2a haplotype (A/J) and H-2d haplotype (BALB/c, DBA/2) did not. In the area of acute focal inflammation in mice with the H-2b and H-2k haplotypes, tachyzoites and toxoplasma antigens were demonstrated by immunoperoxidase staining, suggesting that the focal inflammation was induced by toxoplasma organisms. B10 congenic mice were used for further analysis of this genetic regulation. Presence of the encephalitis in B10 and B10.BR but not in B10.A and B10.D2 mice at 10 weeks after infection indicated regulation of the inflammation by a gene(s) within the H-2 complex. The encephalitis developed in B10.A (2R) and B10.A (4R) mice but not in B10.A (3R) and B10.A (18R) during infection. These results clearly indicated that the development of toxoplasmic encephalitis was controlled by a gene(s) in the H-2D region. The Qa and Tla genes did not appear to be critical in determining susceptibility to the encephalitis. There was no correlation between serum toxoplasma antibody titres and occurrence of the encephalitis. Injection of a monoclonal antibody to interferon-gamma (IFN-gamma) remarkably augmented the inflammatory changes in the brains of the infected B10 mice. In contrast, the treatment did not induce any inflammatory response in the brains of the infected BALB/c mice. A similar genetic regulation may be operative in determining development of toxoplasmic encephalitis in AIDS and other immunocompromised patients.

Role of beta interferon in resistance to Toxoplasma gondii infection.

The role of recombinant murine beta interferon (rMuIFN-beta) and recombinant human IFN-beta (rHuIFN-beta) in resistance to Toxoplasma gondii was examined. rMuIFN-beta protected mice against a lethal infection with the parasite. The protective effect appeared to depend on the concomitant release of gamma interferon. rMuIFN-beta did not activate murine peritoneal macrophages to inhibit or kill T. gondii whether used alone or in combination with lipopolysaccharide (LPS). rHuIFN-beta did not activate human monocyte-derived macrophages to inhibit or kill T. gondii when 5-day-old monocyte-derived macrophages were used. In contrast, significant killing of T. gondii was noted when 10-day-old monocyte-derived macrophages were used. The addition of LPS enhanced this effect. These results revealed a role for IFN-beta in the mechanisms of defense against T. gondii and suggest its potential use in the treatment of toxoplasmosis in humans.

Interferon-gamma: the major mediator of resistance against Toxoplasma gondii.

Mice were injected with a monoclonal antibody to interferon-gamma to examine the importance of endogenous production of this lymphokine in resistance against infection with the sporozoan parasite Toxoplasma gondii. Mice with intraperitoneal infections of T. gondii that received no antibody survived and developed chronic T. gondii infection, whereas the infected mice that received the monoclonal antibody died of toxoplasmosis. The activation of macrophages, which kill T. gondii in vivo, was inhibited by administration of the monoclonal antibody, but the production of antibodies to T. gondii was not suppressed. The fact that an antibody to interferon-gamma can eliminate resistance to acute Toxoplasma infection in mice suggests that this lymphokine is an important mediator of host resistance to this parasite.