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Objectives: Sex differences in adult cellulitis, a frequent cause of hospitalization, have not been analyzed. These differences were investigated in a large cellulitis series. Methods: This was a prospective observational study of 606 Spanish hospitalized cellulitis patients. Different comorbidities, clinical, diagnostic, and treatment data were compared between the sexes. Multiple logistic regression modeling was performed to determine the variables independently associated with sex. Results: Overall 606 adult cellulitis patients were enrolled; 314 (51.8%) were male and 292 (48.2%) were female. Females were older (mean age 68.8 vs 58.9 years, p < 0.0001), less likely to have prior wounds (p = 0.02), and more likely to have venous insufficiency (p = 0.0002) and edema/lymphedema (p = 0.0003) than males. The location of the infection differed between the sexes (p = 0.02). Males were more likely to have positive pus cultures (p = 0.0008), the causing agent identified (p = 0.04), and higher rates of Staphylococcus aureus infection (p = 0.04) and received longer antibiotic treatment (p = 0.03). Factors independently associated with female sex in the multivariate analysis were older age (p < 0.0001), prior cellulitis (p = 0.01), presence of edema/lymphedema as the predisposing factor (p = 0.004), negative versus positive pus culture (p = 0.0002), and location of cellulitis other than in the lower extremities (p = 0.035). Conclusions: Differences between male and female patients with cellulitis were age, recurrence, presence of edema/lymphedema, positivity of pus culture, and topography of the infection.

The aim of this work was to analyze outer membrane porin-encoding genes (ompK35 and ompK36) in a collection of OXA-48 producing Klebsiella pneumoniae, to assess the effect of porin alterations on the susceptibility to ceftazidime/avibactam, and to describe a screening methodology for phenotypic detection of OXA-48-producing K. pneumoniae with disrupted porins. Antimicrobial susceptibility was tested by Microscan and Etest. The genomes of 81 OXA-48-producing K. pneumoniae were sequenced. MLST, detection of antimicrobial resistance genes, and analysis of ompK35 and ompK36 were performed in silico. Tridimensional structures of the OmpK36 variants were assessed. Receiver operating characteristics curves were built to visualize the performance ability of a disk diffusion assay using carbapenems and cefoxitin to detect OmpK36 functional alterations. A wide variety of OmpK36 alterations were detected in 17 OXA-48-producing K. pneumoniae isolates. All displayed a high-level meropenem resistance (MIC ≥ 8 mg/L), and some belonged to high-risk clones, such as ST15 and ST147. Alterations in ompK35 were also observed, but they did not correlate with high-level meropenem resistance. All isolates were susceptible to ceftazidime/avibactam and porin alterations did not affect the MICs of the latter combination. Cefoxitin together with ertapenem/meropenem low inhibition zone diameters (equal or lower than 16 mm) could strongly suggest alterations affecting OmpK36 in OXA-48-producing K. pneumoniae. OXA-48-producing K. pneumoniae with porin disruptions are a cause of concern, ceftazidime/avibactam showed good in vitro activity against them, so this combination could be positioned as the choice therapy to combat the infections caused by this difficult-to-treat isolates.

Mycobacterium kansasii extrapulmonary infections are infrequent in immunocompetent adults. Rifampin (RIF), clarithromycin (CLR), isoniazid (INH) and ethambutol (EMB) are included in all the standard regimens against M.kansasii. We report a case of a healthy 65-year-old male farmer who presented with isolated right supraclavicular lymphadenopathy. The lymph node FNA showed acid-fast-bacilli and granulomatous inflammation. Quantiferon TB Gold test, HIV serology, and functional immunological studies were all negative or normal. He was put on a standard 4 drugs anti-tuberculous regimen that was switched to RIF + CLR+ INH after the Microbiology lab demonstrated an EMB–resistant Mycobacterium kansasii isotype I strain. The patient was cured after 12 months of therapy. This is the 6th reported case of M. kansasii extrapulmonary lymphadenitis in an immunocompetent adult and the 2nd showing EMB resistance in the world literature. Antimycobacterial regimens against M. kansasii, classically resistant to pyrazinamide (PZA) might also exclude EMB due to its increasing resistance in Europe. A 612 months therapy with at least 2 effective antimycobacterial drugs including RIF + CLR might be enough to treat extrapulmonary M. kansasii infections in immunocompetents. Keywords: Mycobacterium kansasii, Cervical lymphadenitis, Immunocompetent, Resistance, Ethambutol, Quantiferon

Mycobacterium kansasii extrapulmonary infections are infrequent in immunocompetent adults. Rifampin (RIF), clarithromycin (CLR), isoniazid (INH) and ethambutol (EMB) are included in all the standard regimens against M.kansasii. We report a case of a healthy 65-year-old male farmer who presented with isolated right supraclavicular lymphadenopathy. The lymph node FNA showed acid-fast-bacilli and granulomatous inflammation. Quantiferon TB Gold test, HIV serology, and functional immunological studies were all negative or normal. He was put on a standard 4 drugs anti-tuberculous regimen that was switched to RIF + CLR+ INH after the Microbiology lab demonstrated an EMB–resistant Mycobacterium kansasii isotype I strain. The patient was cured after 12 months of therapy. This is the 6th reported case of M. kansasii extrapulmonary lymphadenitis in an immunocompetent adult and the 2nd showing EMB resistance in the world literature. Antimycobacterial regimens against M. kansasii, classically resistant to pyrazinamide (PZA) might also exclude EMB due to its increasing resistance in Europe. A 612 months therapy with at least 2 effective antimycobacterial drugs including RIF + CLR might be enough to treat extrapulmonary M. kansasii infections in immunocompetents.

Objectives The aim of the study was to study the factors associated with immunological recovery in HIV-infected patients with suppressed viral load. Methods Nadir and current CD4 cell counts were recorded in 821 patients, as well as many demographic, epidemiological, lifestyle, clinical, therapeutic, genetic, laboratory, liver fibrosis and viral hepatitis parameters. Results The median age of the patients was 44.4 years [interquartile range (IQR) 40.3–48.0 years], the median time since HIV diagnosis was 15.3 years (IQR 10.5–18.9 years), the median time of suppressed viral load was 7.0 years (IQR 4.0–10.0 years) and the median time on the current antiretroviral regimen was 2.8 years (IQR 1.4–4.7 years). The median nadir and current CD4 counts were 193.0 (IQR 84.0–301.0) and 522.0 (IQR 361.0–760) cells/μL, respectively, separated by a median period of 10.2 years (IQR 5.9–12.9 years). The median CD4 count gain during follow-up was 317.0 (IQR 173.0–508.0) cells/μL. Many variables were associated with CD4 cell gains in univariate analyses, including age, gender, epidemiology, prior clinical conditions, fibrosis stage, transient elastometry, aspartate aminotransferase (AST), nadir CD4 count and hepatitis B and C virus infections and genotypes, as well as the durations of follow-up since nadir CD4 count, overall antiretroviral treatment, current antiretroviral regimen, protease inhibitor therapy and suppression of viral load. Multivariate analysis revealed that longer duration of HIV suppression (P < 0.0001), more advanced clinical Centers for Disease Control and Prevention (CDC) stages (P < 0.0001), younger age (P = 0.0003), hepatitis C virus genotypes 1 and 4 (P = 0.003), sexual acquisition of HIV (P = 0.004), and lower transient elastometry values (P = 0.03) were independent predictors of CD4 cell gains. Overall, the model accounted for 14.2% of the variability in CD4 count. Conclusions In addition to the duration of HIV suppression, HIV-related diseases, HIV epidemiology, age, hepatitis C virus genotypes, and liver fibrosis were independently associated with long-term immunological recovery.

Background Cellulitis is a frequent cause of admission of adult patients to medical wards and A/C monotherapy is commonly used as the initial regimen. Studies evaluating the factors associated with the change of this regimen are lacking. Methods Data were extracted from a prospective and observational study of 606 adult patients with cellulitis admitted to several Spanish hospitals. Comorbidities, microbiological, clinical, lab, diagnostic, and treatment data were analyzed and compared according to the continuation/change of A/C. Multiple logistic regression modeling was performed to determine the variables independently associated with A/C switching. Results Overall 259 (42.7%) patients started A/C monotherapy, 56 (21.6%) of which were switched to other antimicrobials. Patients switched from A/C developed sepsis (19.6% vs. 8.4%, P = 0.02) and underwent imaging methods (P < 0.01) more commonly than those kept on A/C. These A/C switched patients had higher serum glucose (P = 0.04), creatinine (P < 0.0001), leukocyte (P = 0.006) and neutrophil counts (P < 0.0001). Regarding microbiological data, patients switched from A/C had more frequently pus (P < 0.0001) and blood cultures (P = 0.002) available, a microorganism identified (P < 0.0001) and higher rates of Gram-negative bacilli infections (P = 0.003). Patients switched from initial A/C had also longer hospitalization stays (10.5 vs. 5.2 days, P < 0.00019, longer duration of IV (10.0 vs. 4.3 days, P < 0.0001), and overall antibiotic treatment (16.5 vs. 10.4 days, P < 0.0001) and needed more frequently surgical treatment (25.0 vs. 4.9%, P < 0.0001), specialized follow-up after discharge (36.4 vs. 17.3%, P = 0.0009) and combination therapy after discharge (35.9% vs. 1.1%, P < 0.0001).The variables independently asociated with A/C switch in the multivariate analysis were higher serum creatinine (P = 0.03), neutrophil counts (P = 0.003), days on IV antibiotics (P < 0.0001) and the needed for surgical treatment (P = 0.004) Conclusion Patients switched from the initial A/C regimen do not have differences in the predisposing factors, but seem to have more serious cellulitis, characterized by higher neutrophil counts and serum creatinine, needing extended IV antibiotic therapy and additional surgical debridement. Disclosures All authors: No reported disclosures.

Background Studies comparing gender differences between cellulitis features are lacking and might be useful for the knowledge, prevention and management of this infection. Methods Prospective, observational, multicenter study of 606 adult patients (314, 51.8% men) with cellulitis. Comorbidities, microbiological, clinical, lab, diagnostic, and treatment data were analyzed. Multiple logistic regression modeling was performed to determine the variables independently associated with gender. Results Women were older (P < 0.0001), less likely to have prior wounds (P = 0.02), and more likely to have venous insufficiency (P = 0.0002), edema/ lymphedema (P < 0.0003) and prior cellulitis episodes than men (P = 0.07). Cellulitis location also differed between genders (P = 0.02). Regarding microbiology, male patients were more likely to have positive pus cultures than women (P = 0.0008), mainly monomicrobial (P = 0.03).There were differences in microorganisms isolated from pus (P = 0.002), with higher S.aureus infection rates among men than women (P = 0.04).Drawing of blood for culture was also more common in men (P = 0.03). Overall, any microorganism (P = 0.006) and the causative microorganism (P = 0.04) were more commonly identified in male than in female patients, due exclusively to the pus culture results, because there were no differences in the positivity of blood cultures (P = 0.9).Of the 61 S.aureus isolates 15 (24.6%) were methicillin-resistant, without significant differences between genders (P = 0.5). Regarding therapy, men had longer treatments (P = 0.03) and higher rates of antibiotic treatment after discharge (P = 0.04). Factors independently associated with female gender in multivariate analysis were:older age (P < 0.0001), prior episodes of cellulitis (P = 0.01), presence of edema/lymphedema as predisposing factor (P = 0.004), negative pus culture (P = 0.0002) and location of cellulitis in thorax/abdomen (P = 0.035) and head/neck (P = 0.0003) as compared with lower extremities Conclusion Cellulitis in women as compared with men present at older ages, recur more frequently, are more commonly related to edema/lymphedema, affect more frequently other locations compared with lower extremities, and have less frequently positive pus cultures. Disclosures All authors: No reported disclosures.

SUMMARY. The role of exposure to antiretrovirals (ARV) and serum matrix metalloproteases (MMPs) on liver fibrosis (LF) progression in human immunodeficiency virus (HIV) mono or HIV‐ hepatitis C virus (HCV) coinfection is unclear. Thus, 213 Caucasian adult HIV-infected patients were studied, 111 of whom had HCV-coinfection and 68 were HCVmonoinfected. Patients with ethanol consumption >50 g/ day, hepatitis B coinfection, non-infective liver diseases or HAART adherence

Background Reliable non-invasive methods for the evaluation of liver fibrosis are desirable, and the risk factors associated with fibrosis are not fully identified. Methods A cross-sectional study of a cohort of 805 HIV–HCV-coinfected patients with active HCV replication, most (95.2%) of whom were intravenous drug users, was conducted. Liver fibrosis was measured by transient elastometry with cutoff values of 7.2 kPa (significant fibrosis), 9.4 kPa (advanced fibrosis) and 14.0 kPa (cirrhosis), and by liver fibrosis indexes (LFI; APRI, Forns and FIB-4). Available liver biopsies were also evaluated. Results The prevalences of significant fibrosis, advanced fibrosis and cirrhosis were 55.8%, 38.4% and 23.5%, respectively. A number of parameters were associated both in the univariate and multivariate analyses with each of the diverse fibrosis groups; however, only six of them were predictive of all stages of fibrosis: heavy alcohol intake (odds ratio [OR] 3.37, 95% confidence interval [CI] 2.02–5.59; PConclusions Elastometry constitutes a useful tool in the diagnosis and follow-up of HIV–HCV-coinfected patients. Fibrosis is associated with diverse factors, some of them treatable or preventable, which need to be addressed considering the high prevalence and course of fibrosis in these patients.

Objective: Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are involved in extracellular matrix remodelling and adipocyte differentiation and are inhibited by antiretrovirals. MMPs and TIMPs and their single nucleotide polymorphisms (SNPs) might contribute to the HAART-related lipodystrophic syndrome pathogenesis. Design and setting: Cross-sectional study in a university-based outpatient clinic. Patients and methods: Two hundred and sixteen HIV-infected patients on extended HAART were studied. Serum MMPs (1, 2, 3, 8, 9, 10, 13) and TIMPs (1, 2, 4) were measured by ELISA microarrays. MMP1 (� 16071G/2G) SNP was also genotyped. Lipodystrophic syndrome was diagnosed by a clinical scale validated by fat dual energy X-ray absorptiometry. Results: Eighty-two patients (38.0%) showed lipodystrophic syndrome, mostly lipoatrophy. The 2G/2G MMP1 SNP genotype was more frequent among lipodystrophic syndrome patients (41.3 vs. 20.5%, odds ratio, 2.73; 95% confidence interval, 1.41‐ 5.29; x 2 ¼9.62, P ¼0.002 for HIV-infected patients with and without lipodystrophic syndrome respectively). Carriers of this genotype had higher serum levels of MMP1 compared with those with the 1G/1G (P ¼0.02). Higher MMP1 (P ¼0.022) and lower TIMP4 (P ¼0.038) serum levels were observed while comparing HIV patients with and without lipodystrophic syndrome. MMP1 2G carriage (P ¼0.0008), TIMP4 lower serum levels (P ¼0.02), treatment with stavudine (P

Summary Matrix metalloproteases (MMPs) are increased in different infections due to their role in controlling immune responses and are regulated by tissue inhibitors (TIMPs). Different MMP promoter single nucleotide polymorphisms (SNPs) induce changes in MMP genes, mRNA and protein expression. Gender might also modify MMP plasma levels. In order to determine the weight of these variables on MMP secretion we studied MMP-1, -2, -3, -8, -9, -10, -13 and TIMP-1, -2, -4 plasma levels in 90 patients with severe bacterial sepsis, 102 with anti-retroviral (ARV)-treated HIV monoinfection, 111 with ARV-treated HIV–hepatitis C virus (HCV) co-infection and 86 non-infected controls (45 stroke and 41 trauma patients). MMP-1(-1607 1G/2G), MMP-3(-1612 5A/6A), MMP-8(-799C/T), MMP-9(-1562 C/T) and MMP-13(-77A/G) SNPs were genotyped. MMP-3 plasma levels were significantly higher in men than in women in each diagnostic group, and MMP-3 SNP allele 6A carriers also had higher levels than allele 5A carriers, an effect that was magnified by sepsis. Independent predictors of higher MMP-3 levels were male gender (P = 0·0001), MMP-3(-1612 5A/6A) SNP (P = 0·001), higher levels of TIMP-4 (P = 0·004) and MMP-8 (P = 0·006) and lower levels of MMP-1 (P = 0·03) by multivariate analysis. No strong associations with gender or SNPs were observed for other MMPs or TIMPs. In conclusion, male gender and MMP-3(-1612 5A/6A) 6A allele carriage increased MMP-3 plasma levels significantly, especially in patients with severe bacterial sepsis. This confounding gender effect needs to be addressed when evaluating MMP-3 plasma levels in any infectious or non-infectious condition.

AIM To investigate the relationships among diverse metalloproteases (MMPs) and their tissue inhibitors (TIMPs) and non-alcoholic liver fibrosis in human immunodeficiency virus (HIV)-infected patients. METHODS Single nucleotide polymorphisms (SNPs) in MMPs, TNF-α and CCR5 genes, and serum levels of MMPs and TIMPs were determined in HIV-infected individuals with/out hepatitis C virus (HCV) coinfection. A total of 158 patients were included, 57 of whom were HCV-coinfected. All patients drank < 50 g ethanol/day. Diverse SNPs (MMP-1 -1607 1G/2G, MMP-8 -799C/T, MMP-9 -1562 C/T, MMP-13 -77A/G, TNF-α -308 G/A, CCR5-∆32), and serum levels of MMPs (2, 3, 8, 9 and 10) and TIMPs (1, 2 and 4) were assessed. Liver fibrosis was determined by transient elastometry, although other non-invasive markers of fibrosis were also considered. Significant liver fibrosis (F ≥ 2) was defined by a transient elastometry value ≥ 7.1 kPa. RESULTS A total of 34 patients (21.5%) had liver fibrosis ≥ F2. MMP-2 and TIMP-2 serum levels were higher in patients with liver fibrosis ≥ F2 (P = 0.02 and P = 0.03, respectively) and correlated positively with transient elastometry values (P = 0.02 and P = 0.0009, respectively), whereas MMP-9 values were negatively correlated with transient elastometry measurements (P = 0.01). Multivariate analyses showed that high levels of MMP-2 (OR = 2.397; 95%CI: 1.191-4.827, P = 0.014) were independently associated with liver fibrosis ≥ F2 in the patients as a whole. MMP-2 (OR = 7.179; 95%CI: 1.210-42.581, P = 0.03) and male gender (OR = 10.040; 95%CI: 1.621-62.11, P = 0.013) were also independent predictors of fibrosis ≥ F2 in the HCV-infected subgroup. Likewise, MMP-2, TIMP-2 and MMP-9 were independently associated with transient elastometry values and other non-invasive markers of liver fibrosis. None of the six SNPs evaluated had any significant association with liver fibrosis ≥ F2. CONCLUSION Certain MMPs and TIMPs, particularly MMP-2, seems to be associated with non-alcoholic liver fibrosis in HIV-infected patients with/without HCV coinfection.

The efficacy of carbapenems versus cefotaxime (8g/day)+metronidazole (1.5-2g/day) [combined standard chemotherapy (CSC)] for the treatment of brain abscess was compared. Fifty-nine adult patients with brain abscesses received either imipenem or meropenem (3-4g/day) or CSC for a mean of 5 weeks, in addition to neurosurgery in most cases. Cure was obtained in 84.7% of cases; 42/47 (89.4%) on carbapenems [18/22 (81.8%) on imipenem versus 24/25 (96.0%) on meropenem] and 8/12 (66.7%) on CSC (P=0.06). Seven patients with multiple abscesses were treated with imipenem (1 died; cure rate 85.7%), five with meropenem (all survived; cure rate 100%) and five with CSC (2 died; cure rate 60%) (P