An Update on Heart Transplantation in Human Immunodeficiency Virus-Infected Patients.

Cardiovascular diseases have become a significant cause of morbidity in patients with human immunodeficiency virus (HIV) infection. Heart transplantation (HT) is a well-established treatment of end-stage heart failure (ESHF) and is performed in selected HIV-infected patients in developed countries. Few data are available on the prognosis of HIV-infected patients undergoing HT in the era of combined antiretroviral therapy (cART) because current evidence is limited to small retrospective cohorts, case series, and case reports. Many HT centers consider HIV infection to be a contraindication for HT; however, in the era of cART, HT recipients with HIV infection seem to achieve satisfactory outcomes without developing HIV-related events. Consequently, selected HIV-infected patients with ESHF who are taking effective cART should be considered candidates for HT. The present review provides epidemiological data on ESHF in HIV-infected patients from all published experience on HT in HIV-infected patients since the beginning of the epidemic. The practical management of these patients is discussed, with emphasis on the challenging issues that must be addressed in the pretransplant (including HIV criteria) and posttransplant periods. Finally, proposals are made for future management and research priorities.

Clinical Presentation and Determinants of Mortality of Invasive Pulmonary Aspergillosis in Kidney Transplant Recipients: A Multinational Cohort Study.

The prognostic factors and optimal therapy for invasive pulmonary aspergillosis (IPA) after kidney transplantation (KT) remain poorly studied. We included in this multinational retrospective study 112 recipients diagnosed with probable (75.0% of cases) or proven (25.0%) IPA between 2000 and 2013. The median interval from transplantation to diagnosis was 230 days. Cough, fever, and expectoration were the most common symptoms at presentation. Bilateral pulmonary involvement was observed in 63.6% of cases. Positivity rates for the galactomannan assay in serum and bronchoalveolar lavage samples were 61.3% and 57.1%, respectively. Aspergillus fumigatus was the most commonly identified species. Six- and 12-week survival rates were 68.8% and 60.7%, respectively, and 22.1% of survivors experienced graft loss. Occurrence of IPA within the first 6 months (hazard ratio [HR]: 2.29; p-value = 0.027) and bilateral involvement at diagnosis (HR: 3.00; p-value = 0.017) were independent predictors for 6-week all-cause mortality, whereas the initial use of a voriconazole-based regimen showed a protective effect (HR: 0.34; p-value = 0.007). The administration of antifungal combination therapy had no apparent impact on outcome. In conclusion, IPA entails a dismal prognosis among KT recipients. Maintaining a low clinical suspicion threshold is key to achieve a prompt diagnosis and to initiate voriconazole therapy.

Risk Factors Associated With Early Invasive Pulmonary Aspergillosis in Kidney Transplant Recipients: Results From a Multinational Matched Case-Control Study.

Risk factors for invasive pulmonary aspergillosis (IPA) after kidney transplantation have been poorly explored. We performed a multinational case-control study that included 51 kidney transplant (KT) recipients diagnosed with early (first 180 posttransplant days) IPA at 19 institutions between 2000 and 2013. Control recipients were matched (1:1 ratio) by center and date of transplantation. Overall mortality among cases was 60.8%, and 25.0% of living recipients experienced graft loss. Pretransplant diagnosis of chronic pulmonary obstructive disease (COPD; odds ratio [OR]: 9.96; 95% confidence interval [CI]: 1.09-90.58; p = 0.041) and delayed graft function (OR: 3.40; 95% CI: 1.08-10.73; p = 0.037) were identified as independent risk factors for IPA among those variables already available in the immediate peritransplant period. The development of bloodstream infection (OR: 18.76; 95% CI: 1.04-339.37; p = 0.047) and acute graft rejection (OR: 40.73, 95% CI: 3.63-456.98; p = 0.003) within the 3 mo prior to the diagnosis of IPA acted as risk factors during the subsequent period. In conclusion, pretransplant COPD, impaired graft function and the occurrence of serious posttransplant infections may be useful to identify KT recipients at the highest risk of early IPA. Future studies should explore the potential benefit of antimold prophylaxis in this group.

Fosfomycin plus ß-Lactams as Synergistic Bactericidal Combinations for Experimental Endocarditis Due to Methicillin-Resistant and Glycopeptide-Intermediate Staphylococcus aureus.

The urgent need of effective therapies for methicillin-resistant Staphylococcus aureus (MRSA) infective endocarditis (IE) is a cause of concern. We aimed to ascertain the in vitro and in vivo activity of the older antibiotic fosfomycin combined with different beta-lactams against MRSA and glycopeptide-intermediate-resistant S. aureus (GISA) strains. Time-kill tests with 10 isolates showed that fosfomycin plus imipenem (FOF+IPM) was the most active evaluated combination. In an aortic valve IE model with two strains (MRSA-277H and GISA-ATCC 700788), the following intravenous regimens were compared: fosfomycin (2 g every 8 h [q8h]) plus imipenem (1 g q6h) or ceftriaxone (2 g q12h) (FOF+CRO) and vancomycin at a standard dose (VAN-SD) (1 g q12h) and a high dose (VAN-HD) (1 g q6h). Whereas a significant reduction of MRSA-227H load in the vegetations (veg) was observed with FOF+IPM compared with VAN-SD (0 [interquartile range [IQR], 0 to 1] versus 2 [IQR, 0 to 5.1] log CFU/g veg; P = 0.01), no statistical differences were found with VAN-HD. In addition, FOF+IPM sterilized more vegetations than VAN-SD (11/15 [73%] versus 5/16 [31%]; P = 0.02). The GISA-ATCC 700788 load in the vegetations was significantly lower after FOF+IPM or FOF+CRO treatment than with VAN-SD (2 [IQR, 0 to 2] and 0 [IQR, 0 to 2] versus 6.5 [IQR, 2 to 6.9] log CFU/g veg; P < 0.01). The number of sterilized vegetations after treatment with FOF+CRO was higher than after treatment with VAN-SD or VAN-HD (8/15 [53%] versus 4/20 [20%] or 4/20 [20%]; P = 0.03). To assess the effect of FOF+IPM on penicillin binding protein (PBP) synthesis, molecular studies were performed, with results showing that FOF+IPM treatment significantly decreased PBP1, PBP2 (but not PBP2a), and PBP3 synthesis. These results allow clinicians to consider the use of FOF+IPM or FOF+CRO to treat MRSA or GISA IE.

Impact of antibiotic resistance on the development of recurrent and relapsing symptomatic urinary tract infection in kidney recipients.

We sought to determine the frequency, risk factors, and clinical impact of recurrent urinary tract infections (UTI) in kidney transplant recipients. Of 867 patients who received a kidney transplant between 2003 and 2010, 174 (20%) presented at least one episode of UTI. Fifty-five patients presented a recurrent UTI (32%) and 78% of them could be also considered relapsing episodes. Recurrent UTI was caused by extended-spectrum betalactamase (ESBL)-producing Klebsiella pneumoniae (31%), followed by non-ESBL producing Escherichia coli (15%), multidrug-resistant (MDR) Pseudomonas aeruginosa (14%), and ESBL-producing E. coli (13%). The variables associated with a higher risk of recurrent UTI were a first or second episode of infection by MDR bacteria (OR 12; 95%CI 528), age >60 years (OR 2.2; 95%CI 1.15.1), and reoperation (OR 3; 95%CI 1.37.1). In addition, more relapses were recorded in patients with UTI caused by MDR organisms than in those with susceptible microorganisms. There were no differences in acute rejection, graft function, graft loss or 1 year mortality between groups. In conclusion, recurrent UTI is frequent among kidney recipients and associated with MDR organism. Classic risk factors for UTI (female gender and diabetes) are absent in kidney recipients, thus highlighting the relevance of uropathogens in this population.

Toxoplasmic encephalitis associated with meningitis in a heart transplant recipient.

Toxoplasma gondii is an opportunistic pathogen that causes neurologic and extraneurologic manifestations in immunosuppressed patients. Encephalitis and intracranial mass lesions are easily recognized as typical manifestations of toxoplasmosis. However, meningitis caused by T. gondii is a rare condition with very few cases described in the literature. We present the case of a heart transplant recipient who developed toxoplasmic encephalitis associated with meningitis. After an extensive review of the medical literature, we found only 1 case of meningitis in solid organ transplant recipients and <25 cases in immunosuppressed patients, such as patients infected with human immunodeficiency virus or those with Hodgkin's disease. In this report, we consider toxoplasmosis in the differential diagnosis of meningitis in immunocompromised individuals.

Late-onset Pneumocystis jirovecii pneumonia in solid organ transplant recipients.

Anti-Pneumocystis prophylaxis is recommended for at least 6-12 months after solid organ transplantation, as most cases of Pneumocystis jirovecii pneumonia (PCP) occur during the first year post transplantation. Herein, we report 4 cases of late-onset PCP (>1 year post transplant). PCP appeared in a range of 50-68 months post transplant. Two cases had history of humoral rejection episodes treated with rituximab, and the other 2 had low CD4+ T-cell count (<200 cells/mm(3) ) at the time of diagnosis. All 4 patients survived. In conclusion, although the number of cases is low, we must be aware of the possibility of late-onset PCP in solid organ transplant patients. The role of previous use of rituximab or persistent CD4+ T-cell lymphopenia should be addressed in future studies.

Daptomycin is safe and effective for the treatment of gram-positive cocci infections in solid organ transplantation.

INTRODUCTION: Infections caused by resistant gram-positive cocci (GPC), especially to glycopeptides, are difficult to treat in solid organ transplant (SOT) recipients as a result of lower effectiveness and high rates of renal impairment. The aim of this study was to evaluate the use of daptomycin in this population. METHODS: Over a 2-year period (March 2008-2010) in 9 Spanish centers, we enrolled all consecutive recipients who received daptomycin to treat GPC infection. The study included 43 patients, mainly liver and kidney transplant recipients. RESULTS: The most frequent infections were catheter-related bacteremia caused by coagulase-negative staphylococci (23.2%), skin infection caused by Staphylococcus aureus (11.5%), and intra-abdominal abscess caused by Enterococcus faecium (20.9%). The daily daptomycin dose was 6 mg/kg in 32 patients (74.4%). On day 7 of daptomycin treatment, median estimated area under the curve was 1251 µg/mL/h. At the end of follow-up, analytical parameters were similar to the values at the start of therapy. No changes were observed in tacrolimus levels. No patient required discontinuation of daptomycin because of adverse effects. Clinical success at treatment completion was achieved in 37 (86%) patients. Three patients died while on treatment with daptomycin. CONCLUSION: In summary, daptomycin was a safe and useful treatment for GPC infection in SOT recipients.

Epidemiology, clinical characteristics, and outcome of invasive aspergillosis in renal transplant patients.

BACKGROUND: Invasive aspergillosis (IA) has been considered an infrequent complication after renal transplantation. We aimed to evaluate the differences in clinical and epidemiologic characteristics of IA between renal and other types of transplantation. METHODS: We reviewed all cases of solid organ transplant (SOT) recipients from Hospital Clinic at Barcelona, who had proven and probable IA, according to the EORTC/MSG criteria, between June 2003 and December 2010. RESULTS: A total of 1762 transplants were performed. From this cohort, 27 cases of IA were diagnosed (1.5%): in 56% (15/27) liver, 33% (9/27) kidney, and 11% (3/27) combined transplant. The median onset time from renal and non-renal transplants to IA was 217 and 10 days, respectively (P < 0.001). There were 6 cases (22%) of late IA (>6 months), all in kidney recipients (P < 0.001). Renal transplant patients with IA more frequently had chronic lung disease (44% vs. 6%) and chronic heart failure (33% vs. 6%); they also had none of the classical risk factors for IA defined for liver transplantation (0% vs. 33%, P = 0.001), and therefore they did not receive antifungal prophylaxis (0% vs. 72%, P = 0.001). In 14/24 patients, serum galactomannan antigen was positive, and this related to higher mortality. CONCLUSIONS: While classical risk factors described for IA in liver recipients are still valid, IA appears later in renal patients and is commonly associated with co-morbid conditions.

Bacterial urinary tract infection after solid organ transplantation in the RESITRA cohort.

BACKGROUND: Urinary tract infection (UTI) is the most common infection in renal transplant patients, but it is necessary to determine the risk factors for bacterial UTI in recipients of other solid organ transplants (SOTs), as well as changes in etiology, clinical presentation, and prognosis. METHODS: In total, 4388 SOT recipients were monitored in 16 transplant centers belonging to the Spanish Network for Research on Infection in Transplantation (RESITRA). The frequency and characteristics of bacterial UTI in transplant patients were obtained prospectively from the cohort (September 2003 to February 2005). RESULTS: A total of 192 patients (4.4%) presented 249 episodes of bacterial UTI (0.23 episodes per 1000 transplantation days); 156 patients were kidney or kidney-pancreas transplant recipients, and 36 patients were liver, heart, and lung transplant recipients. The highest frequency was observed in renal transplants (7.3%). High frequency of cystitis versus pyelonephritis without related mortality was observed in both groups. The most frequent etiology was Escherichia coli (57.8%), with 25.7% producing extended-spectrum ß-lactamase (ESBL). In all transplants but renal, most cases occurred in the first month after transplantation. Cases were uniformly distributed during the first 6 months after transplantation in renal recipients. Age (odds ratio [OR] per decade 1.1, 95% confidence interval [CI] 1.02-1.17), female gender (OR 1.74, 95% CI 1.42-2.13), and the need for immediate post-transplant dialysis (OR 1.63, 95% CI 1.29-2.05) were independent variables associated with bacterial UTI in renal and kidney-pancreas recipients. The independent risk factors identified in non-renal transplants were age (OR per decade 1.79, 95% CI 1.09-3.48), female gender (OR 1.7, 95% CI 1.43-2.49), and diabetes (OR 1.02, 95% CI 1.001-1.040). CONCLUSIONS: UTI was frequent in renal transplants, but also not unusual in non-renal transplants. Because E. coli continues to be the most frequent etiology, the emergence of ESBL-producing strains has been identified as a new problem. In both populations, most cases were cystitis without related mortality. Although the first month after transplantation was a risk period in all transplants, cases were uniformly distributed during the first 6 months in renal transplants. Age and female gender were identified as risk factors for UTI in both populations. Other particular risk factors were the need for immediate post-transplant dialysis in renal transplants and diabetes in non-renal transplants.

Epidemiology and risk factors for late infection in solid organ transplant recipients.

BACKGROUND: Information concerning the risk factors and outcome of late infection (LI) after solid organ transplantation (SOT) still remains scarce. METHODS: We prospectively analyzed all patients undergoing SOT from July 2003 to March 2008, who survived the first 6 months after surgery and with a minimum 1-year follow-up. Risk factors associated with the development of bacterial and cytomegalovirus (CMV) LI and survival were identified. RESULTS: Overall, 942 SOT recipients (491 kidney, 280 liver, 65 heart, and 106 double transplants) were included. During the study period 147 patients (15.6%) developed 276 episodes of LI (incidence rate, 0.43 per 1000 transplantation-days). Bacteria were the most prevalent etiology (88.0%). Primary sources of infection included urinary tract (36.9%), intra-abdominal (16.7%), and sepsis without source (13.4%). Independent risk factors for late bacterial infection were: age (hazard ratio [HR] [per year] 1.0; 95% confidence interval [CI]: 1.0-1,0), female gender (HR 1.7; 95%CI: 1.1-2.6), anti-hepatitis C virus (HCV) positive serostatus (HR 1.8; 95%CI: 1.1-3.0), chronic allograft dysfunction (HR 3.2; 95%CI: 1.7-6.1), early CMV disease (HR 2.2; 95%CI 1.2-4.1), and early bacterial infection (HR 2.5; 95%CI 1.6-3.8). The occurrence of chronic allograft dysfunction was an independent risk factor for late CMV disease (HR 6.5; 95%CI: 1.7-24.6), whereas immunosuppression based on mammalian target of rapamycin inhibitors protected against the development of late CMV disease (HR 0.3; 95%CI: 0.1-1.0). Cox model selected anti-HCV positive serostatus (adjusted HR [aHR] 2.67; 95%CI: 1.27-5.59), age (aHR [per year] 1.06; 95%CI: 1.02-1.10), and the occurrence of LI (aHR 9.12; 95%CI: 3.90-21.33) as independent factors for mortality. CONCLUSIONS: LI did not constitute an uncommon complication in our cohort, and patients at risk may benefit from close clinical monitoring.

Daptomycin is effective for treatment of experimental endocarditis due to methicillin-resistant and glycopeptide-intermediate Staphylococcus epidermidis.

This study evaluated the daptomycin activity against two methicillin-resistant Staphylococcus epidermidis (MRSE) clinical isolates with different vancomycin susceptibilities: MRSE-375, with a vancomycin MIC of 2 microg/ml, and NRS6, a glycopeptide-intermediate S. epidermidis (GISE) strain with a vancomycin MIC of 8 microg/ml. The in vivo activity of daptomycin at two different doses (standard dose [SD-daptomycin], 6 mg/kg of body weight/day intravenously [i.v.]; high dose [HD-daptomycin], 10 mg/kg/day i.v.) was evaluated in a rabbit model of infective endocarditis and compared with that of a standard dose of vancomycin (SD-vancomycin; 1 g i.v. every 12 h) for 2 days. For the MRSE-375 strain, high-dose vancomycin (HD-vancomycin; 1 g i.v. every 6 h) was also studied. For MRSE-375, SD- and HD-daptomycin therapy sterilized significantly more vegetations than SD-vancomycin therapy (9/15 [60%] and 11/15 [73%] vegetations, respectively, versus 3/16 [19%] vegetations; P = 0.02 and P = 0.002, respectively). HD-daptomycin sterilized more vegetations than HD-vancomycin (11/15 [73%] versus 5/15 [33%] vegetations; P = 0.03) and was more effective than SD- and HD-vancomycin in reducing the density of bacteria in valve vegetations (0 log(10) CFU/g vegetation [interquartile range {IQR}, 0 to 1 log(10) CFU/g vegetation] versus 2 log(10) CFU/g vegetation [IQR, 2 to 2 log(10) CFU/g vegetation] and 2 log(10) CFU/g vegetation [IQR, 0 to 2.8 log(10) CFU/g vegetation]; P = 0.002 and P = 0.01, respectively). For the NRS6 strain, SD- and HD-daptomycin were significantly more effective than vancomycin in reducing the density of bacteria in valve vegetations (3.7 log(10) CFU/g vegetation [IQR, 2 to 6 log(10) CFU/g vegetation] versus 7.1 log(10) CFU/g vegetation [IQR, 5.2 to 8.5 log(10) CFU/g vegetation]; P = 0.02). In all treatment arms, isolates recovered from vegetations remained susceptible to daptomycin and vancomycin and had the same MICs. In conclusion, daptomycin at doses of 6 mg/kg/day or 10 mg/kg/day is more effective than vancomycin for the treatment of experimental endocarditis due to MRSE and GISE.

Immunosuppressive therapy and infection after kidney transplantation.

BACKGROUND: The role of immunosuppressive drugs in the development of infection in transplant recipients has been poorly analyzed. OBJECTIVE: To evaluate the possible association between infection and immunosuppression regimens in a large cohort of renal transplant recipients. METHODS: All renal transplant recipients included in the RESITRA prospective cohort from August 2003 to February 2005 with a minimum follow-up of 3 months were studied. An intention-to-treat analysis was performed and patients were analyzed in groups according to the type of induction and initial maintenance therapy. Viral, bacterial, and fungal infections occurring during this period were evaluated. RESULTS: A total of 1398 renal transplant recipients were studied. A maintenance regimen containing sirolimus was independently associated with a lower risk of cytomegalovirus (CMV) infection (odds ratio [OR], 0.16; 95% confidence interval [CI], 0.05-0.54) and with a higher rate of surgical site infection (OR, 3.21; 95% CI, 1.26-8.21). Excluding treatment used for acute rejection episodes, no other factors related to the immunosuppression regimens were associated with the development of bacteremia, urinary infections, pneumonia, or other infections. CONCLUSION: The use of sirolimus as maintenance therapy in kidney recipients is associated with a low rate of CMV infection and with a higher risk of surgical site infection.

Effect of different housing systems (single and group penning) on the health and welfare of commercial female rabbits.

In recent decades, concern about rabbit welfare and sustainability has increased. The housing system is a very important factor for animal welfare. However, information about how different available housing types for female rabbits affect their health status is scarce, but this is an important factor for their welfare. Hence, the objective of this study was to evaluate the health status of female rabbits in five common housing systems: three different single-housing systems with distinct available surfaces and heights; a single-housing system with a platform; a collective system. Female rabbits in the collective and platform cages had greater cortisol concentrations in hair than those in the single-housing system with no platform. Haptoglobin concentrations and kit mortality rates during lactation were greater for the collective-cage female rabbits. The collective group had more culled females and more lesions than in the other groups. The main reasons for culling in all the groups were reproduction problems and presence of abscesses, and the collective group of females was the most affected. In conclusion, it appears that keeping females together in collective systems negatively affects their health status and welfare, while single-housing systems imply lower kit mortality rates during lactation and cortisol concentrations, and fewer lesions in female rabbits.

Consequences of rearing feeding programme on the performance of rabbit females from 1st to 2nd parturition.

To evaluate how rearing programmes could affect resources allocation and reproductive performance of primiparous rabbit females, a total of 118 rabbit females were used to evaluate the effects of five rearing feeding programmes on their performance from 1st to 2nd parturition: CAL, fed ad libitum C diet (11.0 MJ digestible energy (DE), 114 g digestible protein (DP) and 358 g NDF/kg dry matter (DM) until 1st parturition; CR, fed ad libitum with C diet until 12 weeks of age and then C diet restricted (140 g/day) until 1st parturition; F, fed ad libitum with F diet (8.7 MJ DE, 88 g DP and 476 NDF/kg DM) until 1st parturition; FC, fed with F diet ad libitum until 16 weeks of age, and C diet ad libitum until 1st parturition; FCF, fed with F diet ad libitum until 16 weeks of age, then C diet ad libitum until 20 weeks and then F diet ad libitum until 1st parturition. From 1st parturition, C diet was ad libitum offered to all the experimental groups until 2nd parturition. CAL females presented lower feed intake than females of F, FC and FCF groups in the 1st week of lactation (on av. -16.6%; P<0.05). During 1st lactation, the perirenal fat thickness change in CAL females was not different from 0 (+0.02 mm), while in the other four groups it increased (on av. +0.44 mm; P<0.05). Plasma of females fed with F diet during rearing (F, FC and FCF) had lower non-esterified fatty acids content than those exclusively fed with C diet (-0.088 and -0.072 mmol/l compared to CAL and CR, respectively; P<0.05). FCF litters had higher weight than F litters at day 21 of lactation (+247 g; P<0.05), but FCF litter had significantly lower weight than FC litters at weaning (+170 g; P<0.05). CR females had the shortest average interval between the 1st and 2nd parturition (49 days) and FCF females the longest (+ 9 days compared to CR; P<0.05). At 2nd parturition, liveborn litters of F females were larger and heavier than litters of FCF females (+2.22 kits and +138 g; P<0.05), probably due to the lower mortality at birth of F litters (-16.5 percentage points; P<0.05). In conclusion, rearing females on fibrous diets seems to increase the ability of primiparous rabbit females to obtain resources, especially at the onset of lactation.

Risk factors for infection with extended-spectrum and AmpC beta-lactamase-producing gram-negative rods in renal transplantation.

Increasing prevalence of infections caused by multiresistant gram-negative enteric bacilli due to synthesis of extended-spectrum beta-lactamase (ESBL) or to desrepressed chromosomic AmpC beta-lactamase (AmpC) is a major concern in the hospitalized patient population. Renal transplant recipients are especially susceptible to these infections. A cohort observational study in a 3-year period was performed. ESBL-production was determined by phenotypic analysis based on the CLSI recommendations. A multi-variate logistic regression analysis was performed to identify independent variables associated with multi-resistant gram-negative bacilli infection. The study included 417 patients (61 double kidney-pancreas recipients). The incidence of ESBL-producing and desrepressed chromosomic AmpC beta-lactamase resistance was 11.8% (49 patients). The most frequent bacteria isolated was E. coli (35/60 isolations), followed by Klebsiella spp(12/60 isolations). Double kidney-pancreas transplantation(OR 3.5, CI95% 1.6-7.8), previous use of antibiotics(OR 2.1,CI95% 1.1-4.1), posttransplant dialysis requirement (OR 3.1, CI95% 1.5-6.4) and posttransplant urinary obstruction (OR 5.8, CI95% 2.2-14.9) were independent variables associated with these multiresistant gram-negative enteric bacilli infections. The incidence of ESBL-producing and desrepressed AmpC beta-lactamase gram-negative enteric bacilli infection in our population was high. These infections are associated with significant morbidity after renal transplantation.

Virological diagnosis in community-acquired pneumonia in immunocompromised patients.

Community-acquired pneumonia (CAP) is a serious lower respiratory tract infection associated with significant morbidity and mortality in immunocompromised patients. The present study evaluated the clinical spectrum of CAP in immunocompromised hosts and the role of respiratory viruses, as well as the yield of viral diagnostic methods. Conventional microbiological tests were routinely performed in immunocompromised patients with CAP. Nasopharyngeal swabs were processed for respiratory viruses by indirect immunofluorescence assay, cell culture and PCR. Four groups were defined according to aetiology of CAP, as follows: group 1 (nonviral), group 2 (mixed, nonviral and viral), group 3 (only viral) and group 4 (unknown aetiology). Over a 1-yr period, 92 patients were included. An aetiological diagnosis was achieved in 61 (66%) patients: 38 (41%), group 1; 12 (13%), group 2; and 11 (12%), group 3. The most frequent pathogen detected was Streptococcus pneumoniae (n = 29, 48%), followed by rhinovirus (n = 11, 18%). PCR identified 95% of respiratory viruses. Clinical characteristics could not reliably distinguish among the different aetiological groups. Respiratory viruses represent a substantial part of the aetiologies of community-acquired pneumonia in immunocompromised patients and its routine assessment through PCR in nasopharyngeal swabs should be considered in the clinical care of these patients.

Incisional surgical infection in heart transplantation.

BACKGROUND: Incisional surgical site infections (ISSIs) are common bacterial infections in heart transplantation (HT). The purpose of this study was to determine the incidence, etiology, timing, and risk factors for ISSIs. METHODS: A prospective study was performed, which included all heart transplants carried out in the participating hospitals (pertaining to the Spanish National Hospital Network RESITRA) between August 2003 and February 2005. A population of 292 consecutive patients was included (84.9% males). The definition of ISSI used in the study was based on the Centers for Disease Control criteria. RESULTS: Seventeen episodes of ISSIs were recorded in 14 patients (4.8%; confidence interval [CI] 95% 2.7-7.7%). The median time from transplant to ISSI was 14 days (range 3-75). Two patients (14%) died; fatality was related to ISSI (mediastinitis) in 1 patient (7%). Coagulase-negative staphylococci (7 cases), methicillin-resistant Staphylococcus aureus (3 cases), Proteus mirabilis, extended-spectrum beta-lactamase-producing Escherichia coli, Candida albicans, and Candida glabrata, 1 case each, were the isolated pathogens. The duration of extracorporeal circulation was longer in patients with ISSI, although the difference did not reach statistical significance. Antibiotic prophylaxis with ciprofloxacin alone (odds ratio, 15.8; 95% CI, 1.2-216.9) was independently associated with the development of ISSI. CONCLUSIONS: ISSIs in HT are frequently caused by resistant bacteria and Candida, but are associated with good prognosis.

Dual infection in pregnancy: Disseminated Mycoplasma hominis and necrotizing herpes simplex 2 hepatitis.

Mycoplasma hominis is part of the genitourinary flora in sexually active people and can cause disseminated infection in immunocompromised patients. We describe a rare case of an immunocompetent pregnant woman with simultaneous necrotizing HSV hepatitis and disseminated M. hominis infection. Detection of M. hominis and antimicrobial susceptibility testing of this fastidious organism in the clinical laboratory is discussed.

ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Immune checkpoint inhibitors, cell adhesion inhibitors, sphingosine-1-phosphate receptor modulators and proteasome inhibitors).

BACKGROUND: The present review is part of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Infections in Compromised Hosts (ESGICH) consensus document on the safety of targeted and biological therapies. AIMS: To review, from an infectious diseases perspective, the safety profile of immune checkpoint inhibitors, LFA-3-targeted agents, cell adhesion inhibitors, sphingosine-1-phosphate receptor modulators and proteasome inhibitors, and to suggest preventive recommendations. SOURCES: Computer-based Medline searches with MeSH terms pertaining to each agent or therapeutic family. CONTENT: T-lymphocyte-associated antigen 4 (CTLA-4) and programmed death (PD)-1/PD-1 ligand 1 (PD-L1)-targeted agents do not appear to intrinsically increase the risk of infection but can induce immune-related adverse effects requiring additional immunosuppression. Although CD4+ T-cell lymphopenia is associated with alefacept, no opportunistic infections have been observed. Progressive multifocal leukoencephalopathy (PML) may occur during therapy with natalizumab (anti-α4-integrin monoclonal antibody (mAb)) and efalizumab (anti-CD11a mAb), but no cases have been reported to date with vedolizumab (anti-α4ß7 mAb). In patients at high risk for PML (positive anti-JC polyomavirus serology with serum antibody index >1.5 and duration of therapy ≥48 months), the benefit-risk ratio of continuing natalizumab should be carefully considered. Fingolimod induces profound peripheral blood lymphopenia and increases the risk of varicella zoster virus (VZV) infection. Prophylaxis with (val)acyclovir and VZV vaccination should be considered. Proteasome inhibitors also increase the risk of VZV infection, and antiviral prophylaxis with (val)acyclovir is recommended. Anti-Pneumocystis prophylaxis may be considered in myeloma multiple patients with additional risk factors (i.e. high-dose corticosteroids). IMPLICATIONS: Clinicians should be aware of the risk of immune-related adverse effects and PML in patients receiving immune checkpoint and cell adhesion inhibitors respectively.