Superinfection In Patients Research Articles

Stability of Antibiotics in Portable Pumps Used for Bronchial Superinfection: Guidelines for Prescribers

The aims of this study were (1) to collect data on the stability of antibiotics in portable pumps for the treatment of bronchial superinfection in patients with cystic fibrosis and (2) to provide guidelines for prescribers. The stability over 72 hours, in portable pumps stored at 35 degrees C, of piperacillin plus tazobactam, ticarcillin plus clavulanic acid, cefsulodin, cefepime, and aztreonam was checked at 3 different concentrations. Stability was assessed through visual examination, pH measurements, and direct measurements of drug concentrations by using high-performance liquid chromatography. All parameters were measured at time 0, time 0 plus 24 hours, and time 0 plus 72 hours. Degradation rates for penicillin plus beta-lactamase inhibitor combinations remained <10% at time 0 plus 24 hours for all drugs, but the rate for piperacillin reached 12% for the highest concentration tested. The cephalosporins cefepime and cefsulodin had significant respective degradation rates of 18% and 28% at time 0 plus 24 hours and 60% and 68.5% at time 0 plus 72 hours, which were linked to the storage temperature. Aztreonam seemed to be stable over 72 hours. This work provides data on drug stability that were lacking, allowing recommendations for physicians to optimize the safety and efficacy of antibiotic treatment of patients with cystic fibrosis. Piperacillin plus tazobactam and ticarcillin plus clavulanic acid infusions must be limited to 24 hours, and patients receiving cefepime or cefsulodin must wear a cold pack close to the ambulatory drug-delivery device during the infusion.

Coinfection and Superinfection in Patients with Long‐Term, Nonprogressive HIV‐1 Disease

Human immunodeficiency virus 1 (HIV-1) dual infections are considered important because they have been related to AIDS progression. We identified dual infections in 2 patients with long-term, nonprogressive HIV-1 disease; the first patient was diagnosed as being already coinfected, on the basis of the first sample analyzed, but a previous superinfection could not be excluded; the second patient was diagnosed as having a superinfection, on the basis of the 9-year difference between the viral dating of the 2 strains. Dual infections occur in patients with long-term, nonprogressive disease, with no immediate clinical manifestations. Such occurrences could indicate a general phenomenon in natural HIV-1 infections.

Hepatitis A virus infection suppresses hepatitis C virus replication and may lead to clearance of HCV

The significance of hepatitis A virus (HAV) super-infection in patients with chronic hepatitis C had been a matter of debate. While some studies suggested an incidence of fulminant hepatitis A of up to 35%, this could not be confirmed by others. We identified 17 anti-HCV-positive patients with acute hepatitis A from a cohort of 3170 anti-HCV-positive patients recruited at a single center over a period of 12 years. Importantly, none of the anti-HCV-positive patients had a fulminant course of hepatitis A. HCV-RNA was detected by PCR in 84% of the anti-HCV-positive/anti-HAV-IgM-negative patients but only in 65% of anti-HCV-positive patients with acute hepatitis A (p=0.03), indicating suppression of HCV replication during hepatitis A. Previous HAV infection had no effect on HCV replication. After recovery from hepatitis A, an increased HCV replication could be demonstrated for 6 out of 9 patients with serial quantitative HCV-RNA values available while 2 patients remained HCV-RNA negative after clearance of HAV throughout follow-up of at least 2 years. HAV super-infection is associated with decreased HCV-RNA replication which may lead to recovery from HCV in some individuals. Fulminant hepatitis A is not frequent in patients with chronic hepatitis C recruited at a tertiary referral center.

High Incidence of Genotypic Variance between Sequential Herpes Simplex Virus Type 2 Isolates from HIV‐1–Seropositive Patients with Recurrent Genital Herpes

We developed a polymerase chain reaction (PCR) method, based on strain-to-strain variation of DNA repeats in the herpes simplex virus type 2 (HSV-2) genes US1 and US12, to genotype HSV-2 strains and determine the incidence and risk factors associated with HSV-2 superinfection in patients with recurrent genital herpes (RGH). Forty-seven (92%) of 51 unrelated HSV-2 isolates could be distinguished. Genotyping of sequential HSV-2 isolates showed a different genotype in all of the 11 human immunodeficiency virus type 1 (HIV-1)-seropositive patients with RGH, compared with 1 of the 8 HIV-1-seronegative patients with RGH. The PCR approach developed distinguishes unrelated HSV-2 strains efficiently and indicated a high incidence of genotype variance between sequential HSV-2 isolates of HIV-1-seropositive patients with RGH.

Traitement des surinfections bronchiques: stabilité des antibiotiques dans les diffuseurs portatifs

AbstractTreatment of Bronchial Superinfections: Data Related to Stability of Antibiotics in Portable Pumps. Introduction.Given many data about the stability of antibiotics in portable pump (elastomer) are lacking, this study was designed to make a point about available data and to evaluate the stability of antibiotics when exposed to temperature within 35°C (average temperature measured in real conditions of use). Material and methodsFirst, to collect information about the stability of antibiotics in portable pump and to confront them with the local antibiotics protocols dedicated to the treatment of bronchial superinfection in patients with cystic fibrosis; second, to evaluate the stability of piperacillin associated with tazobactam at 35°C. ResultsWhile measured concentrations in tazobactam did not show significant variation during the study, piperacillin measurements showed a major reduction of concentration (up to 33%), both time and concentration related to. DiscussionSuch information must be pointed out to prescribers and patients to ensure a cold accumulator is placed in the pump can’ying-bag and to limit the duration of infusion to 24h with a single pump. ConclusionThis experimental program will keep on going with the stability study of both ticarcillin and cefsulodin in portable pump.

An Update on Hdv: Virology, Pathogenesis and Treatment

Hepatitis delta is an inflammatory liver disease caused by infection with HDV. HDV is a single-stranded circular RNA pathogen with a diameter of 36 nm. HDV is classified in the genus Deltavirus and is still awaiting a final taxonomic classification up to the family level. HDV shares similarities with satellite RNA and viroids including a small circular single-stranded RNA with secondary structure that replicates through the 'double rolling circle' mechanism. The HDV RNA genome is capable of self-cleavage through a ribozyme and encodes only one structural protein, the hepatitis delta antigen (HDAg), from the antigenomic RNA. There are two forms of HDAg, a shorter (S; 22 kDa) and a longer (L; 24 kDa) form, the latter generated from an RNA editing mechanism. The S form is essential for viral genomic replication. The L form participates in the assembly and formation of HDV. For complete replication and transmission, HDV requires the hepatitis B surface antigen (HBsAg). Thus, HDV infection only occurs in HBsAg-positive individuals, either as acute coinfection in treatment-naive HBV-infected persons, or as superinfection in patients with pre-existing chronic hepatitis B (CHB). HDV is found throughout the world, but its prevalence, incidence, clinical features and epidemiological characteristics vary by geographic region. There are eight genotypes (1 to 8) distributed over different geographic areas: HDV-1 is distributed worldwide, whereas HDV-2 to 8 are seen more regionally. Levels of HDV viraemia change over the course of HDV infection, being significantly higher in patients with early chronic hepatitis than in cirrhosis. Chronic HDV infection leads to more severe liver disease than chronic HBV monoinfection with an accelerated course of fibrosis progression, an increased risk of hepatocellular carcinoma and early decompensation in the setting of established cirrhosis. Current treatments include pegylated interferon-α and liver transplantation; the latter of which can be curative. Further studies are needed to develop better treatment strategies for this challenging disease.

Clinical efficacy of intramuscular vaccinia immune globulin: a literature review.

Numerous literature reports describe clinical efficacy of intramuscular vaccinia immune globulin (VIG) for complications of smallpox vaccination, prophylaxis of individuals with contraindications to vaccination, and prevention of smallpox among close contacts of patients with smallpox. We reviewed the literature regarding VIG treatment and prophylaxis of smallpox vaccine complications and the use of VIG as a preventative measure for close contacts of patients with smallpox. Data regarding intramuscular administration of VIG for treatment of smallpox vaccine complications occurred in 16 articles, none of which reported formal controlled trials. The indications for treatment include generalized vaccinia, progressive vaccinia, eczema vaccinatum, and certain accidental implantations. Six publications suggest VIG efficacy for prophylaxis of vaccinial superinfection of eczema, burns, chickenpox, immunosuppression, pregnancy, or certain skin conditions. Prophylactic VIG has also been used in healthy military recruits to reduce the incidence of postvaccinial encephalitis. The use of intramuscular administration of VIG to prevent smallpox in contacts of patients with documented cases of smallpox is reported in 4 studies that compare contacts who received intramuscular administration of VIG with those who did not and in 1 observational study, with varying but promising results. Although controlled clinical trials do not exist to support the use of VIG for treatment of vaccinia-related complications or prophylaxis among individuals with contraindications to smallpox vaccination, available data suggest that VIG reduces morbidity and mortality associated with progressive vaccinia (vaccinia necrosum) and eczema vaccinatum. Furthermore, VIG seems to prevent vaccinial superinfection in patients with inflammatory skin diseases or burns, given the low incidence of vaccina-related complications associated with these conditions.

Genotypic analysis of sequential genital herpes simplex virus type 1 (HSV-1) isolates of patients with recurrent HSV-1 associated genital herpes.

Clinical recurrences of Herpes simplex virus type 1 (HSV-1)-associated genital herpes are thought to be caused by reactivation of latent endogenous HSV-1. However, the possibility of reinfection with exogenous HSV-1 cannot be excluded. This study aimed to determine the incidence of genital HSV-1 superinfection in patients by investigating the genotype of sequential HSV-1 isolates obtained from the same anatomical site of patients with clinical recurrences of genital HSV-1 recurrent genital herpes. Sequential genital HSV-1 isolates were genotyped by PCR amplification of the hypervariable regions located within the HSV-1 genes US1 and US12. Whereas the sequential HSV-1 isolates in 11 of the 13 patients studied had the same genotypes, the sequential isolates of 2 patients showed a different genotype. The data suggest that HSV-1-induced recurrent genital herpes can be associated with genital reinfection with an exogenous HSV-1 strain.

Impact of acute hepatitis C virus superinfection in patients with chronic hepatitis B virus infection

Background & Aims: Superinfection in patients with chronic hepatitis B virus (HBV) infection is not uncommon. Acute hepatitis delta virus (HDV) superinfection is associated with severe and/or progressive liver disease. The natural course following acute hepatitis C virus (HCV) superinfection has not been well studied. The aim of this study was to investigate the impact of acute HCV superinfection. Methods: The clinical features during acute phase and long-term outcomes of acute HCV superinfection were studied and compared with a cohort of acute HDV superinfection and a matched control group of active chronic hepatitis B. Results: Acute HCV superinfection typically occurs as acute icteric hepatitis. The severity is similar to acute HDV superinfection in that hepatic decompensation developed in 34% of patients, hepatitis failure occurred in 11%, and 10% died. During a follow-up period of 1–21 years, patients with acute HCV superinfection had a significantly higher cumulated incidence of cirrhosis (48% at 10 years) and hepatocellular carcinoma (14% at 10 years, 21% at 15 years, and 32% at 20 years) than acute HDV superinfection or active chronic hepatitis B. Hepatitis B surface antigen (HBsAg) seroclearance occurred earlier in HCV superinfected patients. Continuing hepatitis after HBsAg seroclearance was observed only in HCV superinfected patients. Conclusions: Acute HCV superinfection in patients with chronic HBV infection is clinically severe during its acute phase. The long-term prognosis following acute HCV superinfection is much worse than that following HDV superinfection or active hepatitis B in terms of continuing hepatitis activity after HBsAg loss and the development of cirrhosis or hepatocellular carcinoma.

Hepatitis E virus superinfection in patients with chronic liver disease

Infection with hepatitis A virus (HAV) can cause severe illness in adult patients with chronic liver disease (CLD) caused by hepatitis C. In endemic areas such as South Asia, however, most adult patients already have been exposed to HAV but could still be susceptible to hepatitis E virus (HEV) infection. We document that HEV superinfection in 4 of our CLD patients caused severe liver decompensation. We then determined the seroprevalence of HAV and HEV in 233 patients with stable CLD, with the goal of defining the need for protection against these viruses in these patients. Overall, 41 (17.5%) of 233 CLD patients were HEV antibody immunoglobulin G (IgG)–positive, and 228 of 233 (97.8%) were HAV IgG–positive. As controls, we tested 90 age- and sex-matched healthy volunteer blood donors for HAV and HEV antibodies IgG. There was no difference in the percentage of CLD patients and blood donors positive for HEV antibody IgG (17.7% vs. 17.5%) or for HAV IgG (97.8% vs. 94%). No differences were observed in the severity of liver disease between previously HEV-exposed and -nonexposed patients. In conclusion, superinfection with HEV in patients with underlying CLD can cause severe hepatic decompensation leading to increased morbidity and mortality. The large majority of adult CLD patients in endemic countries are vulnerable to infection with HEV, but are protected against hepatitis A, and are ideal candidates for an HEV vaccine. (H EPATOLOGY 2002;36:474-478.)

Hepatitis C virus superinfection in patients with chronic hepatitis B virus infection.

Because hepatitis B virus (HBV) and hepatitis C virus (HCV) have the same transmission routes, dual infection may occur and even persist in the same patient. The reported series on seroprevalence of HCV indicate that HCV is found in more than 10% of HBV-infected patients worldwide. HCV superinfection in patients with chronic HBV infection tends to cause severe and progressive liver disease that is resistant to interferon therapy. Paradoxically, HCV exerts a suppressive effect on HBV and may enhance seroclearance of HBV antigens, or even usurp the role of HBV as the agent for continuing hepatitis. In view of the complex dynamism of viral interaction, the importance of HCV assay and the necessity of monitoring patients with chronic HBV infection in clinical studies cannot be overemphasized. The basic mechanisms that regulate the viral interactions largely remain to be investigated.

Clinical, virological, immunological, and pathological significance of GB virus C/hepatitis G infection in patients with chronic hepatitis C

GB virus-C (GBV-C)/hepatitis G virus (HGV), a single-strand RNA virus, has been identified as a transfusion transmissible virus and categorized as a member of the Flaviridiae family. GBV-C/HGV superinfection in patients with chronic hepatitis C is not seen uncommonly, most likely because of the similar transmission routes. This study aimed to investigate the prevalence of GBV-C/HGV infection in 100 Chinese patients with histologically proven chronic hepatitis C, and to clarify the clinical, virological, immunological, and histopathological impact of GBV-C/HGV infection on chronic hepatitis C patients. Serum GBV-C/HGV RNA was positive in 22 (22%) of the 100 chronic hepatitis C patients. There were no significant differences in mean age, gender, and serum liver biochemical tests between GBV-C/HGV infected and non-infected chronic hepatitis C patients. The HCV genotype distribution and mean serum HCV RNA level were not significantly different between patients with and without GBV-C/HGV co-infection. The presence of serum autoantibodies (anti-nuclear antibody and anti-smooth muscle antibody) and cryoglobulinemia showed no significant difference between the two groups. Liver histopathological analysis revealed no significant difference in the grade of periportal, portal, and intralobular necro-inflammation, in the stage of fibrosis/cirrhosis, or in the presence of steatosis and lymphoid aggregation/follicle formation between patients with and without GBV-C/HGV infection. However, a higher degree of bile duct damage was noted in chronic hepatitis C patients co-infected with GBV-C/HGV infection than in those without infection ( P=0.036). In conclusion, GBV-C/HGV infection had no apparent influence on the clinical, immunological, or virologic features of patients with chronic hepatitis C. However, the clinical significance of a higher degree of bile duct damage in patients with HCV and GBV-C/HGV co-infection deserves further investigation.

Impact of acute hepatitis B virus superinfection on chronic hepatitis C virus infection.

Hepatitis B virus (HBV) and hepatitis C virus (HCV) dual infection is not uncommon, but the impact of acute HBV superinfection in patients with chronic HCV infection is still unknown. Two patients with well documented chronic HCV infection were hospitalized for acute hepatitis, which was serologically confirmed to be acute HBV superinfection. One patient who was seropositive for both HBV-DNA and HCV-RNA upon admission died of hepatic failure. The other became seronegative for HCV-RNA and recovered with alanine aminotransferase normalization, seroclearance of HBsAg, and antibodies to HCV. These findings confirm that acute superinfection in patients with chronic hepatitis may increase the risk for severe hepatitis, and suggest that HBV as the newcomer may suppress the pre-existing HCV. Together with the earlier observation that acute HCV superinfection suppresses pre-existing HBV, it seems that the timing or sequence of infection is a factor influencing the outcome of viral interactions.

Impact of acute hepatitis B virus superinfection on chronic hepatitis c virus infection

Hepatitis B virus (HBV) and hepatitis C virus (HCV) dual infection is not uncommon, but the impact of acute HBV superinfection in patients with chronic HCV infection is still unknown. Two patients with well documented chronic HCV infection were hospitalized for acute hepatitis, which was serologically confirmed to be acute HBV superinfection. One patient who was seropositive for both HBV-DNA and HCV-RNA upon admission died of hepatic failure. The other became seronegative for HCV-RNA and recovered with alanine aminotransferase normalization, seroclearance of HBsAg, and antibodies to HCV. These findings confirm that acute superinfection in patients with chronic hepatitis may increase the risk for severe hepatitis, and suggest that HBV as the newcomer may suppress the pre-existing HCV. Together with the earlier observation that acute HCV superinfection suppresses pre-existing HBV, it seems that the timing or sequence of infection is a factor influencing the outcome of viral interactions.

Fluconazole penetration into the pancreas.

Because of antibiotic prophylaxis for necrotizing pancreatitis, the frequency of fungal superinfection in patients with pancreatic necrosis is increasing. In this study we analyzed the penetration of fluconazole into the human pancreas and in experimental acute pancreatitis. In human pancreatic tissues, the mean fluconazole concentration was 8.19 +/- 3.38 microg/g (96% of the corresponding concentration in serum). In experimental edematous and necrotizing pancreatitis, 88 and 91% of the serum fluconazole concentration was found in the pancreas. These data show that fluconazole penetration into the pancreas is sufficient to prevent and/or treat fungal contamination in patients with pancreatic necrosis.

Clinical implications of TT virus superinfection in patients with chronic hepatitis C

OBJECTIVE: TT virus (TTV) has been identified as a candidate agent of non-A–E hepatitis virus. We investigated superinfection of TTV in patients with chronic hepatitis C and studied the susceptibility to interferon (IFN) treatment and its association with liver disease caused by hepatitis C virus (HCV). METHODS: TTV DNA was examined using the seminested polymerase chain reaction (PCR), and its virus level was measured by the real-time fluorometric PCR. RESULTS: TTV DNA was detected in 20 of 102 (19.6%) patients examined. There was no significant difference in the alanine aminotransferase (ALT) level between patients with or without TTV DNA. Quantitative analysis of HCV RNA and TTV DNA revealed no correlation between virus levels in HCV/TTV-coinfected patients. Both TTV and HCV were sensitive to IFN therapy. Complete response to IFN with a sustained loss of viremia for 24 wk after completion of IFN treatment was found in 11 of 20 (55%) patients with respect to TTV DNA and in five of 20 (25%) patients with respect to HCV RNA. The mean pretreatment HCV RNA level was significantly lower in the complete-response cases than in the no-response cases, but there was no significant difference in the pretreatment TTV DNA levels between them. ALT normalization resulting from IFN therapy was not attributable to the eradication of TTV DNA but was attributable to that of HCV RNA. Superinfection by TTV did not influence the effect of IFN against HCV. No specific TTV genotype correlating with IFN sensitivity was found. CONCLUSIONS: These results suggest that TTV infection stands independent of HCV infection, with no influence on liver injury as a result of HCV infection.

Fulminant Hepatitis A in Patients with Chronic Liver Disease

Fulminant hepatitis is a rare complication of acute hepatitis A virus (HAV) infection. We report three cases of fulminant hepatic failure with death due to HAV infection in patients with pre-existing chronic liver disease. Data from the literature also indicate a high case fatality rate during HAV superinfection in patients with chronic hepatitis B, particularly those with cirrhosis, and in patients with alcoholic cirrhosis. In patients with chronic hepatitis C, results are conflicting with some reports indicating a high fatality rate of HAV superinfection and others not, irrespective of the presence or absence of cirrhosis. Based on our observations and this review of the literature, we suggest that patients with chronic liver disease should be vaccinated against hepatitis A.

Fulminant hepatitis associated with hepatitis A virus superinfection in patients with chronic hepatitis C.

There have been conflicting reports of the clinical outcome of acute hepatitis A virus (HAV) infection in patients with chronic hepatitis C virus (HCV) infection. A prospective study evaluated 432 patients with chronic hepatitis C (183 with cirrhosis) over a 7-year period. Of the 17 patients with concurrent HAV infection, seven developed fulminant hepatitis and six died. None of these patients had cirrhosis; however, the HLA phenotype (A1; B8:DR3) appeared to be a significant factor in the development of fulminant hepatitis. Patients with this phenotype had high titres of antinuclear antibodies, antismooth muscle antibodies and antiasialoglycoprotein-receptor antibodies, possibly reflecting the induction of autoimmune hepatitis in this group. The high frequency of fulminant hepatitis in patients with HAV/HCV coinfection contrasts with other surveys, although a large Centers for Disease Control and Prevention (CDC) survey demonstrated that HAV infection in patients with pre-existing chronic liver disease (CLD) is associated with increased mortality. It is likely that CLD has some importance as an underlying factor in the development of fulminant hepatitis following HAV infection. Further prospective studies are needed to clarify this issue.

Treatment of gastrointestinal infections

This review highlights recent reports of new developments in the treatment of gastrointestinal infections. Data are emerging that indicate at least one subset of dyspeptic patients may benefit from treatment to eradicate Helicobacter pylori. Several studies of regimens used to treat H. pylori infection provide incremental improvements to classic triple therapy. Efforts made to improve the World Health Organization oral rehydration solution tend to support various substitutions for the glucose component but do not as yet demonstrate compelling superiority. Promising new approaches to the treatment of recurrent Clostridium difficile infections include the addition of yeast to standard antibiotic regimens and the binding of toxin receptors by synthetic oligosaccharide sequences. Comparisons of patient responses to different approaches for treating esophageal and intestinal superinfections in patients with HIV provide additional insight into the evaluation and management of these patients. Finally, trimethoprim-sulfamethoxazole appears to be emerging as the treatment of choice for the newly recognized parasitic pathogen Cyclospora.

Mucocutaneous and soft tissue infections caused by Xanthomonas maltophilia. A new spectrum.

To describe the mucocutaneous and soft tissue infections caused by Xanthomonas maltophilia in patients with cancer. A retrospective 15-month clinical study. Academic, referral-based cancer center. Of 237 patients with X. maltophilia isolated from all sites during the 15-month study period, 114 patients were judged to have true X. maltophilia infections. Only patients with mucocutaneous and soft tissue infections were included in the study. 17 (15%) of the 114 patients with X. maltophilia infection had mucocutaneous and soft tissue infections: Six patients had metastatic cellulitis, 5 had primary cellulitis usually associated with catheter use, and 6 had infected mucocutaneous ulcers. The metastatic cellulitis consisted of previously undescribed multiple, hard, tender nodules with surrounding and distant cellulitis (5 patients) or ecthyma gangrenosum (1 patient). Four of these patients died of the infection. Metastatic cellulitis and mucocutaneous infections occurred in hospitalized, neutropenic patients who received broad-spectrum antibiotics (beta-lactams, quinolones), often with in vitro activity against the infecting organisms. Response usually correlated with recovery from myelosuppression and administration of trimethoprim-sulfamethoxazole with or without ticarcillin-clavulanate. Catheter removal contributed to response in the treatment of primary cellulitis. Mucocutaneous and soft tissue infections caused by X. maltophilia are not uncommon, and X. maltophilia can cause metastatic nodular skin lesions that mimic disseminated fungal infections. It also causes serious morbidity and high mortality in patients with metastatic skin nodules and can cause superinfections in patients receiving broad-spectrum beta-lactam or quinolone antibiotics to which the organisms are susceptible when the infections develop. Catheter removal contributes to a favorable outcome in patients with catheter-associated cellulitis without bacteremia. Xanthomonas maltophilia infection should be added to the differential diagnosis of mucocutaneous or soft tissue infection in patients with cancer. Trimethoprim-sulfamethoxazole with or without ticarcillin-clavulanate is the current treatment of choice for culture-proven infections, but early empiric therapy may improve outcome.