Time to abandon ampicillin plus gentamicin in favour of ampicillin plus ceftriaxone in Enterococcus faecalis infective endocarditis? A meta-analysis of comparative trials.

BACKGROUND: Current guidelines recommend either ampicillin plus ceftriaxone (AC) or amoxicillin/ampicillin plus gentamicin (AG) with an equivalent class IB recommendation in Enterococcus faecalis endocarditis. However, previous observational studies suggest that AC might be favourable in terms of adverse events. OBJECTIVES: To investigate whether AC is non-inferior to AG, and if it is associated with less adverse events. METHODS: In June 2021, a systematic literature search using the databases PubMed/MEDLINE, CDSR, CENTRAL, CCAs, EBM Reviews, Web of Science and LILACS was conducted by two independent reviewers. Studies were considered eligible if (P) patients included were ≥ 18 years of age and had IE with E. faecalis, (I) treatment with AC was compared to (C) treatment with AG and (O) outcomes on in-hospital mortality, nephrotoxicity and adverse events requiring drug withdrawal were reported. Odds ratios and 95% confidence intervals were calculated using random-effects models with the Mantel-Haenszel method, the Sidik-Jonkman estimator for τ2 and the Hartung-Knapp adjustment. RESULTS: Treatment with AC was non-inferior to AG, as depicted by no significant differences in-hospital mortality, 3-month mortality, relapses or treatment failure. Furthermore, AC was associated with a lower prevalence of nephrotoxicity (OR 0.45 [0.26-0.77], p = 0.0182) and drug withdrawal due to adverse events (OR 0.11 [0.03-0.46], p = 0.0160) than AG. CONCLUSIONS: Treatment with AC was non-inferior to treatment with AG, and it was associated with a reduced prevalence of nephrotoxicity and drug withdrawal due to adverse events. Thus, combination therapy with AC appears favourable over AG in patients with E. faecalis IE.

Characterization of infections and hypogammaglobulinemia treated with the combination of pertuzumab and trastuzumab.

PURPOSE: We update a patient series that reported a high incidence of infection with Gram-positive cocci in women treated with the combination of pertuzumab and trastuzumab and further characterize this clinical problem. PATIENTS: Treating physicians and advanced practice partners identified women who developed infections while on treatment with pertuzumab and trastuzumab alone or in combination with chemotherapy and enrolled them onto this registry trial. RESULTS: Between March, 2014 and May, 2017, 48 patients with HER2-positive breast cancers were reported to have 59 individual infections. The median age was 48 years. Twenty-four patients received neoadjuvant therapy, 17 were treated for metastatic disease, and 7 were treated in the adjuvant setting. Pertuzumab and trastuzumab were combined with carboplatin and docetaxel in 24 (49%) patients, docetaxel in 10 (21%), nab-paclitaxel in 12 (24%), and without other agents in 2 (4%). Granulocyte growth factors were administered in 24 (49%) patients and no patients were documented to be neutropenic. Folliculitis developed in 25 (52%) patients and was counted as a single infection. Abscesses developed at a number of sites in 24 (49%) patients, including a septic knee requiring total knee replacement. Paronychia occurred in 7 (15%) patients, and 5 (10%) developed cellulitis. When cultures were obtained, Gram-positive cocci were consistently identified. Hypogammaglobulinemia was documented in 14 (36%) of the 33 patients tested. CONCLUSIONS: Our data continue to support an increased risk of infections with Gram-positive cocci as a potentially serious adverse event in women treated with pertuzumab and trastuzumab.

Chronic lead (Pb) exposure results in diminished hemocyte count and increased susceptibility to bacterial infection in Drosophila melanogaster.

Heavy metal Pb is a common toxic pollutant present in our environment adversely affecting health of the living organisms. Recent studies suggest positive correlation between heavy metal exposure and immune dysfunction and present work utilizes Drosophila to address this issue in relation to Pb exposure. In-vivo Pb toxicity was established by dietary intake where essential parameters like development and life span were found to be hampered and augmented upon metallothionein B (mtnB) downregulation hinting towards potential role of mtnB in Pb detoxification. Further response of Drosophila to B. subtilis bacterial infection was monitored by carrying out oral infections. Pb fed flies showed increased susceptibility to infection as compared to their controls. Since Drosophila hemocytes play dual role as immune cells, we checked for the total hemocyte count and found significant decrease in hemocyte numbers in Pb fed larvae. Both crystal cells and plasmatocytes, the two major hemocytes in third instar larval hemolymph were reduced. However we did not find any visible morphological changes in Giemsa stained hemocytes. Crystal cells are crucial for synthesis and release of phenoloxidase (PO), an enzyme required for melanin clot synthesis and deposition. PO activity assessed from total hemolymph protein isolates was found to be substantially decreased in Pb raised animals. Results were also confirmed by spot test and native gel activity assay of PO. Overall our results suggest immunotoxic effect of Pb through decrease in hemocyte count including crystal cell which in turn leads to decreased PO activity and increased susceptibility to B. subtilis.

Patterns of infectious complications in acute myeloid leukemia and myelodysplastic syndromes patients treated with 10-day decitabine regimen.

Decitabine has been explored as a reduced-intensity therapy for older or unfit patients with acute myeloid leukemia (AML). To better understand the risk of infections during decitabine treatment, we retrospectively examined the culture results from each infection-related serious adverse event that occurred among 85 AML and myelodysplastic syndromes (MDS) patients treated in a prospective clinical study using 10-day cycles of decitabine at Washington University School of Medicine. Culture results were available for 163 infection-related complications that occurred in 70 patients: 90 (55.2%) events were culture-negative, 32 (19.6%) were gram-positive bacteria, 20 (12.3%) were gram-negative bacteria, 12 (7.4%) were mixed, 6 (3.7%) were viral, 2 (1.2%) were fungal, and 1 (0.6%) was mycobacterial. Infection-related mortality occurred in 3/24 (13%) of gram-negative events, and 0/51 gram-positive events. On average, nearly one third of patients experienced an infection-related complication with each cycle, and the incidence did not decrease during later cycles. In summary, in patients receiving 10-day decitabine, infectious complications are common and may occur during any cycle of therapy. Although febrile events are commonly culture-negative, gram-positive infections are the most frequent source of culture-positive infections, but gram-negative infections represent a significant risk of mortality in AML and MDS patients treated with decitabine.

Tumour necrosis factor (TNF) inhibitor-induced isolated pleural granulomas: a rare adverse effect.

A 53-year-old man with a history of Crohn's disease on infliximab, presented with several weeks of cough and dyspnoea. He had a right-sided pleural effusion, found to be exudative with lymphocytic predominance. He underwent right-sided video-assisted thoracic surgery (VATS) with biopsies and pleurodesis. Histopathology showed pleural-based non-caseating granulomas with unremarkable lung parenchyma. Cultures were only positive for Propionibacterium acnes 8 months later, he was found to have a left-sided exudative, lymphocytic predominant pleural effusion. Left-sided VATS and biopsies again showed pleural-based non-caseating granulomas with normal lung parenchyma. Having ruled out an active infection and malignant lesions, we diagnosed infliximab-induced pleural granulomas. Infliximab was stopped. The patient continues to do well at 6 years of follow-up. We believe this is the first report of tumour necrosis factor (TNF) inhibitor-induced isolated pleural granulomas. P. acnes and cytokine imbalance might be responsible for the pathogenesis of TNF inhibitor-induced granulomas.

[Severe pain and livid discoloration in the left leg of a 32-year-old patient after intravascular heroin injection]. / Massive Schmerzen und livide Verfärbung des linken Beins nach intravaskulärer Heroininjektion bei einem 32-jährigen Patienten.

Acute leg ischemia after intra-arterial drug injection represents a critical vascular emergency scenario. Due to lack of evidence-based standards therapeutic strategies are oriented to the underlying pathomechanisms. For a sufficient therapy a close clinical monitoring and laboratory analyses as well as treatment with analgesics, anticoagulants, anti-inflammatory and spasmolytic agents are of utmost importance. This article reports on the diagnostic and therapeutic approaches in a 32-year-old patient with acute leg ischemia after intra-arterial administration of heroin and secondary infection with Peptostreptococcus and Peptoniphilus species.

Microbiological analysis of epidermal growth factor receptor inhibitor therapy-associated paronychia.

BACKGROUND: Paronychia is a well-known, but difficult to treat cutaneous toxicity associated with epidermal growth factor receptor (EGFR) inhibitor therapy. Although bacterial and fungal infections as well as mechanical trauma may play a role as co-pathogens, there is no good basis for an empirical antimicrobial chemotherapy in these patients. MATERIALS AND METHODS: We retrospectively analysed the microbiological results and resistance analysis of 42 cases of EGFR inhibitor-associated paronychia induced by cetuximab. RESULTS: We identified 20 different species, among these 72% Gram-positive bacteria, 23% Gram-negative bacteria and 5%Candida species. About half of the microbes identified may be considered as residential bacterial flora of the skin, but isolation of microbes from paronychia may indicate a pathogenic relevance for this type of reaction. Eight of our patients were treated with oral antibiotics, whereas two patients received oral antimycotic therapy. All other cases of paronychia were controlled using topical antiseptic, antibiotic and antimycotic agents. CONCLUSION: Empirical oral antibiotic treatment may be performed with oral cephalosporines, ciprofloxacin, levofloxacin or moxifloxacin, as these antimicrobials have high in vitro activity against the majority of the isolated microorganisms and reach high concentrations in the relevant tissue.

Does diclofenac increase the risk of cervical necrotizing fasciitis in a rat model?

Non-steroidal anti-inflammatory drugs (NSAIDs) are known for aggravating in vitro infections and were reported in many cases of cervical necrotizing fasciitis (CNF). We developed a rat model of CNF, mimicking as closely as possible the human-CNF, to study the effect of a NSAIDs, diclofenac, as a promoting factor. Twenty rats were injected bilaterally in the neck with peptostreptococcus and with a fresh saliva specimen for another 20 rats. Half of each group was given an intramuscular injection of 4 mg/kg diclofenac at the time of inoculation and 24 h later, and the other half saline injections; rats were killed at day 7 and clinical, bacterial and histological studies were performed to assess the infectious process and the incidence of CNF. No statistically significant difference was found between groups treated with diclofenac vs. the saline injection groups. However a significant correlation was noted between clinical observation, bacterial density and histological signs of inflammation. CNF has a high mortality rate and the use of NSAIDs in conditions potentially leading to CNF is very common. However, our rat model does not support the hypothesis of a promoting role of diclofenac which was occasionally suggested in the medical literature. This study suggests that diclofenac does not seem to increase the risk of occurrence of CNF. Nonetheless, NSAIDs can mask inflammatory signs of an already spreading CNF.

Incidence of bacterial and fungal infections in newly diagnosed acute myeloid leukaemia patients younger than 65 yr treated with induction regimens including fludarabine: retrospective analysis of 224 cases.

OBJECTIVES: Infections are the major cause of morbidity and mortality in patients with acute myeloid leukaemia (AML). They primarily occur during the first course of induction chemotherapy and may increase the risk of leukaemia relapse, due to a significant delay in consolidation therapy. The intensification of induction chemotherapy and the use of non-conventional drugs such as fludarabine are considered responsible for the increased risk of infections. METHODS: In this study, we retrospectively analysed the infections occurred in 224 newly diagnosed AML patients

[Clinical study of pulmonary infection in kidney transplantation recipients taking new immunosuppressant].

OBJECTIVE: To explore the etiopathogenesis, therapy and incidence of pulmonary infection in kidney transplantation recipients taking new immunosuppressant. METHODS: The clinical data from 752 kidney transplant recipients were retrospectively analyzed, who were divided into 3 groups according to the immunosuppressants administered, namely group A (CsA+MMF+Pred, n=226), group B (FK506+MMF+Pred, n=386) and group C (FK506+Rap+Pred, n=140). The incidence and mortality of pulmonary infection were recorded and the analysis of etiopathogenesis, diagnosis and therapy of pulmonary infection were carried out in the 3 groups. RESULTS: Fifty-three patients acquired post-transplant pulmonary infection. The incidence of pulmonary infection was 7.08% (16/226) in group A, 7.25% (28/386) in group B and 6.43% (9/140) in group C. One patient died in group A and 2 in group B. Among the 53 patients, 24 had simple bacterial infection, 9 had cytomegalovirus infection, 1 had mycotic infection, 17 had combined infection, and 2 had unidentified pathogen infection. Of the pathogenic bacteria detected, 68.35% were Gram-negative. CONCLUSION: Gram-negative bacteria are most likely responsible for pulmonary infection after kidney transplantation, which most possibly occurs within 6 months after kidney transplantation. Early diagnosis and early treatment are critical for decreasing the mortality of severe pneumonia and for improving the survival rate of the patients and grafts.

Infections associated with tumor necrosis factor-alpha antagonists.

Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine involved in a wide range of important physiologic processes. This cytokine has a pathologic role in some diseases, and TNF-alpha antagonists are effective in treating inflammatory conditions. Given the putative role of TNF-alpha in host defense against tuberculosis and other infections, the risk of infection with TNF-alpha antagonists is a concern. Therefore, we searched the literature for reports of tuberculosis and other infections associated with TNF-alpha-antagonist therapy. Although tuberculosis was rarely reported in randomized clinical comparisons of these antagonists, case reports and submissions to the MedWatch program of the United States Food and Drug Administration have been numerous. Most instances were associated with infliximab, but etanercept and adalimumab may also be associated with an increased risk of tuberculosis. Histoplasmosis, listeriosis, aspergillosis, coccidioidomycosis, and candidiasis have been associated with TNF-alpha antagonists, but the causative relationship is not clear. Potential recipients of these drugs should be rigorously screened with skin testing, detailed questioning about recent travel and potential tuberculosis exposure, assessment for symptoms such as cough and weight loss, and chest radiography to minimize their risk of acquiring or reactivating tuberculosis. As with other immunosuppressant drugs, TNF-alpha antagonists should not be given to patients with active infection.

Relations between the consumption of antimicrobial growth promoters and the occurrence of resistance among Enterococcus faecium isolated from broilers.

The present study investigates, at farm level, the effect of the time-span between sampling and the last time a particular antimicrobial growth promoter (AGP) was included in the feed on the probability of selecting an AGP-resistant Enterococcus faecium isolate from a broiler flock. The probability that a randomly selected E. faecium isolate was resistant to avilamycin, erythromycin or virginiamycin was 0.91, 0.92 and 0.84, respectively if the isolate originated from a broiler flock fed either avilamycin- or virginiamycin-supplemented feed. As the time-span between sampling and the last AGP consumption increased, the probability of isolating an E. faecium isolate resistant to a particular AGP decreased (probability <0.2 within 3-5 years after last exposure to AGPs). The decrease in probability over time showed little farm-to-farm variation. The number of times a particular AGP was given to previous flocks reared in the same house had no effect on the probability of isolating a resistant isolate.

Fatal pulmonary hemorrhage associated with micrococcal infection in two children with acute lymphoblastic leukemia.

Pulmonary hemorrhage is a rare cause of death in patients with acute leukemia. Within a 2-month period the authors observed two fatal pediatric cases, which were associated with opportunistic organisms of the genus Micrococcus. Both patients were receiving consolidation treatment for acute lymphoblastic leukemia. The authors discuss the causes of pulmonary hemorrhage in patients with leukemia and review the relevant literature. Micrococci have previously been considered as non-pathogenic, but there is considerable evidence for morbidity and mortality occurring, particularly in immunocompromised patients. The authors propose that micrococcal infection may have been a major predisposing factor for pulmonary hemorrhage in these thrombocytopenic patients.

Clostridium difficile infection and concurrent vancomycin-resistant Enterococcus stool colonization in a health care worker: case report and review of the literature.

Clostridium Difficile diarrhea was noted in a previously healthy health care worker from the study institution after receiving oral clindamycin therapy; the worker also had vancomycin-resistant Enterococcus stool colonization. Health care workers should be aware that antibiotic therapy may place them at increased risk for colonization and infection with nosocomial pathogens such as Clostridium difficile and vancomycin-resistant Enterococcus.

Substituting dexamethasone for prednisone complicates remission induction in children with acute lymphoblastic leukemia.

BACKGROUND: The authors report the occurrence of fatal or near-fatal sepsis in 16 of 38 children with newly diagnosed acute lymphoblastic leukemia (ALL) treated with a new induction regimen that differed from its predecessor by the substitution of dexamethasone for prednisone. METHODS: The frequency of septic deaths among 38 children who received multiagent remission induction therapy, including dexamethasone (6 mg/m(2)) daily for 28 days (pilot protocol 91-01P), was compared with the frequency of septic deaths among children previously treated (protocol 87-01) and subsequently treated (protocol 91-01) in consecutive Dana-Farber Cancer Institute (DFCI) ALL trials with induction therapy that included 21 and 28 days of prednisone (40 mg/m(2)), respectively. Except for dexamethasone in protocol 91-01P, the remission induction agents used were identical in substance to those used in protocol 87-01. Protocol 91-01, the successor 91-01P, was also similar, with the exception of the deletion of a single dose of L-asparaginase. RESULTS: Sixteen of the 38 children (42%) treated on the DFCI 91-01P had documented gram positive or gram negative sepsis (17 episodes) during remission induction, including 4 toxic deaths (11%). In contrast, there were 4 induction deaths among 369 children (1%) treated on protocol 87-01 (P = 0.0035) and 1 induction death among 377 children (<1%) treated on protocol 91-01 (P = 0.0003). CONCLUSIONS: Substitution of dexamethasone for prednisone or methylprednisolone in an otherwise intensive conventional induction regimen for previously untreated children with ALL resulted in an alarmingly high incidence of septic episodes and toxic deaths. Awareness of this complication, considering that the substitution has no apparent benefit in the efficacy of remission induction, argues against its routine use in intensive induction regimens for children with ALL.

Vancomycin-resistant Enterococcus faecium in a Veterans Affairs Medical Center: association with antibiotic usage.

BACKGROUND: Colonization and infection with vancomycin-resistant Enterococcus faecium (VREF) has been associated with the use of vancomycin and other antibiotics in individual patients. The objective of this study was to determine the association of VREF with the aggregate usage of antibiotics on nursing units in a hospital. METHODS: This was a retrospective correlation study. A usage ratio was calculated for each parenteral antibiotic on each nursing unit as the per-bed usage by weight of that antibiotic divided by its average usage throughout the hospital. An average usage ratio (AUR) for each nursing unit was calculated as the mean of usage ratios of individual antibiotics. The AUR was used to compare the usage of antibiotics among nursing units in the hospital. The incidence of VREF infections on individual nursing units in a Veterans Affairs Medical Center was correlated with the usage of parenteral antibiotics separately and in aggregate in univariate and multivariate regression analyses. RESULTS: The AUR was strongly and positively correlated with the recovery of VREF on individual nursing units. By univariate analyses, increasing use of each antibiotic tested was associated with isolation of VREF but only clindamycin remained significant in the multivariate model. However, usage of various antibiotics was highly interrelated, and only clindamycin usage was significantly correlated with usage of all other antibiotics studied. Intensive care and acute care units and units with fewer patient beds were more likely to have patients with VREF infection than were subacute care units (p < 0.003) or larger units (p < 0.01). CONCLUSIONS: VREF infections were associated with greater aggregate antibiotic use on nursing units. Determination of antibiotic usage ratios may provide a convenient and useful tool for examining the association of antibiotic usage with other nosocomial infections.