Pharmacokinetic/pharmacodynamic evaluation of the antimicrobial therapy of pneumococcal invasive disease in adults in post-PCV13 vaccine period in Madrid, Spain.

The objective of our study was to evaluate by pharmacokinetic/pharmacodynamic (PK/PD) analysis, if the antimicrobials used for the treatment of invasive pneumococcal disease (IPD) in adults, including meningitis, are adequate considering the susceptibility profile of S. pneumoniae in Spain after the implantation of PVC13 vaccine. Pharmacokinetic parameters of benzylpenicillin and cefotaxime were obtained from the literature, and susceptibility data of invasive S. pneumoniae strains recovered in 2017 (post-PCV13 vaccination period) were provided by the Public Health Regional Laboratory of Madrid. We have also studied levofloxacin because it is used to treat pneumococcal pneumonia previously to be diagnosed as bacteremic pneumonia. Monte Carlo simulation was used to estimate the probability of target attainment (PTA) and the cumulative fraction of response (CFR). All doses of benzylpenicillin except 2 mU q6h provide a high probability of treatment success for MIC values ≤ 1 mg/L; 4 mU q4h is even useful for MIC values up to 4 mg/L. This high dose, used for the treatment of meningitis, also provides high probability of treatment success for MIC ≤ 0.5 mg/L. At the susceptibility EUCAST breakpoint (≤ 0.5 mg/L), cefotaxime provides a high rate of PD target achievement, even at the lowest dose (1 g q8h). For meningitis, 2 g q6h ensures probabilities of target attainment ≥90% for MIC up to 1 mg/L. Our study confirms that after the implementation of PCV13 vaccine, the treatment with benzylpenicillin and cefotaxime provides high probability of the therapy success of IPD, including meningitis.

Benzylpenicillin versus wide-spectrum beta-lactam antibiotics as empirical treatment of Haemophilus influenzae-associated lower respiratory tract infections in adults; a retrospective propensity score-matched study.

There is consensus that definitive therapy for infections with H. influenzae should include antimicrobial agents with clinical breakpoints against the bacterium. In Scandinavia, benzylpenicillin is the recommended empirical treatment for community-acquired pneumonia (CAP) except in very severe cases. However, the effect of benzylpenicillin on H. influenzae infections has been debated. The aim of this study was to compare the outcomes of patients given benzylpenicillin with patients given wide-spectrum beta-lactams (WSBL) as empirical treatment of lower respiratory tract H. influenzae infections requiring hospital care. We identified 481 adults hospitalized with lower respiratory tract infection by H. influenzae, bacteremic and non-bacteremic. Overall, 30-day mortality was 9% (42/481). Thirty-day mortality, 30-day readmission rates, and early clinical response rates were compared in patients receiving benzylpenicillin (n = 199) and a WSBL (n = 213) as empirical monotherapy. After adjusting for potential confounders, empirical benzylpenicillin treatment was not associated with higher 30-day mortality neither in a multivariate logistic regression (aOR 2.03 for WSBL compared to benzylpenicillin, 95% CI 0.91-4.50, p = 0.082), nor in a propensity score-matched analysis (aOR 2.14, 95% CI 0.93-4.92, p = 0.075). Readmission rates did not significantly differ between the study groups, but early clinical response rates were significantly higher in the WSBL group (aOR 2.28, 95% CI 1.21-4.31, p = 0.011), albeit still high in both groups (84 vs 81%). In conclusion, despite early clinical response rates being slightly lower for benzylpenicillin compared to WSBL, we found no support for increased mortality or readmission rates in patients empirically treated with benzylpenicillin for lower respiratory tract infections by H. influenzae.

The efficacy of high-dose penicillin G for pneumococcal pneumonia diagnosed based on initial comprehensive assessment at admission: an observational study.

OBJECTIVES: High-dose penicillin therapy is effective in approximately 90% of pneumococcal pneumonia cases diagnosed based on urinary pneumococcal antigen tests or Gram staining at admission. The efficacy of high-dose penicillin therapy for pneumococcal pneumonia diagnosed based on an initial comprehensive assessment comprising a syndromic approach, Gram staining of sputum and urinary pneumococcal antigen testing was investigated. RESULTS: Seventy adult patients diagnosed with pneumococcal pneumonia based on an initial comprehensive assessment and treated with high-dose penicillin G at admission were included. The median patient age was 76.5 years, and 37.1% of the patients were women. The urinary pneumococcal antigen test was positive in 67.1% of all patients, and Gram staining of sputum showed that gram-positive cocci were dominant in 58.6% of the patients. The primary outcome was treatment success based on vital signs until day 6. Treatment with high-dose penicillin G was effective in 87.1% of the patients (95% CI 79.1-95.2%), and the proportion of patients who received other antibiotics because of treatment failure with penicillin G was only 5.7%. The efficacy of high-dose penicillin G treatment for pneumococcal pneumonia diagnosed based on a comprehensive assessment at admission may be comparable to that in previous reports.

Neutropenia induced by high-dose intravenous benzylpenicillin in treating neurosyphilis: Does it really matter?

BACKGROUND: Prompt therapy with high-dose intravenous benzylpenicillin for a prolonged period is critical for neurosyphilis patients to avoid irreversible sequelae. However, life-threatening neutropenia has been reported as a complication of prolonged therapy with high doses of benzylpenicillin when treating other diseases. This study aimed to investigate the incidence, presentation, management and prognosis of benzylpenicillin-induced neutropenia in treating neurosyphilis based on a large sample of syphilis patients in Shanghai. METHODOLOGY/PRINCIPAL FINDINGS: Between 1st January 2013 and 31st December 2015, 1367 patients with neurosyphilis were treated with benzylpenicillin, 578 of whom were eligible for recruitment to this study. Among patients without medical co-morbidities, the total incidence of benzylpenicillin-induced neutropenia and severe neutropenia was 2.42% (95% CI: 1.38-4.13%) and 0.35% (95% CI: 0.06-1.39%), respectively. The treatment duration before onset of neutropenia ranged from 10 to 14 days, with a total cumulative dose of between 240 and 324 megaunits of benzylpenicillin. Neutropenia was accompanied by symptoms of chills and fever (5 patients), fatigue (2 patients), cough (1 patient), sore throat (1 patient), diarrhea (1 patient) and erythematous rash (1 patient). The severity of neutropenia was not associated with age, gender or type of neurosyphilis (p>0.05). Neutropenia, even when severe, was often tolerated and normalized within one week. A more serious neutropenia did not occur when reinstituting benzylpenicillin in patients with mild or moderate neutropenia nor when ceftriaxone was used three months after patients had previously experienced severe neutropenia. CONCLUSIONS/SIGNIFICANCE: Benzylpenicillin-induced neutropenia was uncommon in our cohort of patients. Continuation of therapy was possible with intensive surveillance for those with mild or moderate neutropenia. For severe neutropenia, it is not essential to aggressively use hematopoietic growth factors or broad-spectrum antibiotics for patients in good physical condition after withdrawing anti-neurosyphilis regimen. We did not see an exacerbation of neutropenia in patients with the readministration of benzylpenicillin.

Penicillin G Treatment in Infective Endocarditis Patients - Does Standard Dosing Result in Therapeutic Plasma Concentrations?

Penicillin G is frequently used to treat infective endocarditis (IE) caused by streptococci, penicillin-susceptible staphylococci and enterococci. Appropriate antibiotic exposure is essential for survival and reduces the risk of complications and drug resistance development. We determined penicillin G plasma concentration [p-penicillin] once weekly in 46 IE patients. The aim was to evaluate whether penicillin G 3 g every 6 hr (q6 h) resulted in therapeutic concentrations and to analyse potential factors that influence inter- and intra-individual variability, using linear regression and a random coefficient model. [P-penicillin] at 3 hr and at 6 hr was compared with the minimal inhibitory concentration (MIC) of the bacteria isolated from blood cultures to evaluate the following PK/PD targets: 50% fT > MIC and 100% fT > MIC. [P-penicillin] varied notably between patients and was associated with age, weight, p-creatinine and estimated creatinine clearance (eCLcr). Additionally, an increase in [p-penicillin] during the treatment period showed strong correlation with age, a low eCLcr, a low weight and a low p-albumin. Of the 46 patients, 96% had [p-penicillin] that resulted in 50% fT > MIC, while 71% had [p-penicillin] resulting in 100% fT > MIC. The majority of patients not achieving the 100% fT > MIC target were infected with enterococci. Streptococci and staphylococci isolated from blood cultures were highly susceptible to penicillin G. Our results suggest that penicillin G 3 g q6 h is suitable to treat IE caused by streptococci and penicillin-susceptible staphylococci, but caution must be taken when the infection is caused by enterococci. When treating enterococci, therapeutic drug monitoring should be applied to optimize penicillin G dosing and exposure.

Penicillin Encephalopathy: An Unlikely Adversary in the Treatment of Neurosyphilis--Case Report and Review of the Literature.

UNLABELLED: Penicillin encephalopathy is a rare, potentially reversible phenomenon of drug-induced neurotoxicity. CASE: A 65-year-old female with a history of HIV was admitted with a three-day history of worsening headache, confusion, and lethargy. On examination she was awake but confused. Cerebrospinal fluid (CSF) and serum venereal disease research laboratory (VDRL) test returned positive and the patient was started on intravenous penicillin G with probenecid. On the second day of therapy, she developed myoclonic jerking, consistent with penicillin neurotoxicity. Repeat labs also showed new onset renal failure. Penicillin and probenecid therapy were stopped with a resolution of symptoms. Subsequently, therapy without probenecid was reinstituted uneventfully. DISCUSSION: Herein, we describe a female who developed penicillin neurotoxicity after initiation of intravenous penicillin therapy with probenecid for neurosyphilis. It is important that penicillin-induced toxicity be considered if characteristic myoclonic movements accompany encephalopathy. The presence of coexistent renal compromise should heighten the vigilance of clinicians.

A case of ileocecal actinomycosis treated by preoperative antibiotic treatment to reduce mass size followed by surgical resection.

A 65-year-old woman presented to a nearby clinic with a painful mass in the right lower abdominal region. She was suspected of having an appendiceal tumor on abdominal computed tomography (CT) and was referred to our hospital for surgery. Blood testing revealed increased inflammatory markers. Contrast-enhanced abdominal CT revealed a mass with poorly defined margins in the ileocecal region, which was adjacent to the external iliac vessels. A barium enema revealed unilateral wall deformities in the cecum through to the terminal ileum, whereas lower gastrointestinal endoscopy showed no clear epithelial tumor component. The patient was clinically diagnosed with ileocecal actinomycosis and treated with high-dose penicillin G. On day 15 of treatment, contrast-enhanced abdominal CT showed a reduction in mass size. On day 26, right hemicolectomy (D3) with combined resection of the external iliac vein (which could not be separated from the mass) was performed. Pathological examination revealed granulation tissue with granules of actinomyces, with filamentous bacteria detected by Grocott staining. With no evidence of malignancy, the final diagnosis of ileocecal actinomycosis was made. This report presents a case of clinically suspected ileocecal actinomycosis treated by preoperative antibiotic treatment to reduce mass size, followed by surgical resection.

Detecting drug-herbal interaction using a spontaneous reporting system database: an example with benzylpenicillin and qingkailing injection.

PURPOSE: The study aims to quantify anaphylaxis signal for combined exposure of benzylpenicilin and qingkailing injection (QI) compared with individual exposure of the two drugs and the background risk based on all other exposures in SRS database. METHODS: Data used in this study were collected during 2003-2014 from China Guangdong Provincial Center of ADR Monitoring. We studied the suspected ADR reports using a case/non-case design. The cases were defined as the reactions coded by WHO-preferred terms of anaphylactic shock or anaphylactoid reaction. Reporting odds ratios (RORs) were used as a measure of disproportionality and were adjusted for age and gender to reduce confounding effects. An observed-to-expected ratio Ω was also used for interaction detection. RESULTS: The crude RORs (95 % CIs) for anaphylaxis in patients who used only benzylpenicillin or QI and those who used the two drugs concomitantly compared with patients who used neither of the two drugs were 2.50 (2.34-2.68), 1.59 (1.46-1.73), and 6.22 (3.34-11.58), respectively. The adjusted RORs (95 % CIs) were 2.48 (2.31-2.65), 1.54 (1.41-1.67), and 6.01 (3.22-11.20), respectively, after being adjusted for age and gender. The measured Ω, Ω0, Ω025, and Ω975 was 1.03, 1.09, 0.14, and 1.71, respectively. CONCLUSIONS: Case reports in the database are suggestive of a safety signal which indicates that an interaction between benzylpenicillin and QI resulting in excess risk of anaphylaxis may occur. SRS databases have a potential for signaling unknown drug-herbal interactions. More effort is needed to expand this potential.

Antibiotic delivery by liposomes from prokaryotic microorganisms: Similia cum similis works better.

To date the effectiveness of antibiotics is undermined by microbial resistance, threatening public health worldwide. Enhancing the efficacy of the current antibiotic arsenal is an alternative strategy. The administration of antimicrobials encapsulated in nanocarriers, such as liposomes, is considered a viable option, though with some drawbacks related to limited affinity between conventional liposomes and bacterial membranes. Here we propose a novel "top-down" procedure to prepare unconventional liposomes from the membranes of prokaryotes (PD-liposomes). These vectors, being obtained from bacteria with limited growth requirements, also represent low-cost systems for scalable biotechnology production. In depth physico-chemical characterization, carried out with dynamic light scattering (DLS) and Small Angle X-ray Scattering (SAXS), indicated that PD-liposomes can be suitable for the employment as antibiotic vectors. Specifically, DLS showed that the mean diameter of loaded liposomes was ∼200-300nm, while SAXS showed that the structure was similar to conventional liposomes, thus allowing a direct comparison with more standard liposomal formulations. Compared to free penicillin G, PD-liposomes loaded with penicillin G showed minimal inhibitory concentrations against E. coli that were up to 16-times lower. Noteworthy, the extent of the bacterial growth inhibition was found to depend on the microorganisms from which liposomes were derived.

Effect of 3',5'-cyclic diguanylic acid in a broiler Clostridium perfringens infection model.

In an effort to explore strategies to control Clostridium perfringens, we investigated the synergistic effect of a ubiquitous bacterial second messenger 3',5'-cyclic diguanylic acid (c-di-GMP) with penicillin G in a broiler challenge model. All chicks were inoculated in the crop by gavage on d 14, 15, and 16 with a mixture of 4 C. perfringens strains. Birds were treated with saline (control group) or 20 nmol of c-di-GMP by gavage or intramuscularly (IM) on d 24, all in conjunction with penicillin G in water for 5 d. Weekly samplings of ceca and ileum were performed on d 21 to 35 for C. perfringens and Lactobacillus enumeration. On d 35 of age, the IM treatment significantly (P < 0.05) reduced C. perfringens in the ceca, suggesting possible synergistic activity between penicillin G and c-di-GMP against C. perfringens in broiler ceca. Moreover, analysis of ceca DNA for the presence of a series of C. perfringens virulence genes showed a prevalence of 30% for the Clostridium perfringens alpha-toxin gene (cpa) from d 21 to 35 in the IM-treated group, whereas the occurrence of the cpa gene increased from 10 to 60% in the other 2 groups (control and gavage) from d 21 to 35. Detection of ß-lactamase genes (blaCMY-2, blaSHV, and blaTEM) indicative of gram-negative bacteria in the same samples from d 21 to 35 did not show significant treatment effects. Amplified fragment-length polymorphism showed a predominant 92% similarity between the ceca of 21-d-old control birds and the 35-d-old IM-treated c-di-GMP group. This suggests that c-di-GMP IM treatment might be effective at restoring the normal microflora of the host on d 35 after being challenged by C. perfringens. Our results suggest that c-di-GMP can reduce the colonization of C. perfringens in the gut without increasing the selection pressure for some ß-lactamase genes or altering the commensal bacterial population.

Cerebrospinal fluid shunt infection due to Gemella haemolysans.

Gemella haemolysans has long been considered a commensal in the human upper respiratory tract. Commensals are natural inhabitants on or within another organism, deriving benefit without harming or benefiting the host. Opportunistic infection of the CNS by the species is exceedingly rare. In the present case, a 16-year-old boy was admitted with a ventriculoperitoneal shunt infection, which was confirmed to be due to G. haemolysans. Following antibiotic treatment, removal of the old shunt, and delayed insertion of a new shunt, the patient made a full neurological recovery. To the authors' knowledge, this is the eighth case of CNS infection with G. haemolysans. Although prosthesis-related infections have been reported in other systems, this is the first case of CNS infection by the bacterium associated with an implant. Previous reported cases of CNS infection by G. haemolysans are reviewed. Due to the variable Gram staining property of the organism, the difficulty in diagnosing G. haemolysans infection is emphasized.

Evolutionary changes in antimicrobial resistance of invasive Neisseria meningitidis isolates in Belgium from 2000 to 2010: increasing prevalence of penicillin nonsusceptibility.

This study was conducted to evaluate the evolution of the antimicrobial susceptibility of Neisseria meningitidis causing invasive diseases in Belgium in the period of January 2000 to December 2010. A total of 1,933 cases of N. meningitidis from invasive infections were analyzed by antimicrobial susceptibility testing at the Belgian Meningococcal Reference Centre. The majority of strains were susceptible to antibiotics that are currently used for the treatment and prophylaxis of meningococcal disease, but the prevalence of clinical isolates with reduced susceptibility to penicillin increased over the years. The phenotyping, genotyping, and determination of MICs of penicillin G were performed. The systematic shift of the curves toward higher penicillin MICs in the susceptible population indicated that this population became less sensitive to penicillin in this period. A 402-bp DNA fragment in the 3' end of penA was sequenced for the 296 nonsusceptible meningococcal strains isolated between 2000 and 2010 to examine the genetic diversity and evolution of their penA gene. In conclusion, the data obtained in our study support the statement that the position of penicillin G as a first choice in the treatment of invasive meningococcal diseases in Belgium should be reexamined. Despite an important number of isolates displaying a reduced susceptibility to penicillin, at present the expanded-spectrum cephalosporins, such as ceftriaxone, are not affected. The follow-up of the evolutionary changes in antimicrobial resistance has also proved to be essential for the recommendation of an appropriate antimicrobial treatment for invasive meningococcal diseases.

Decreased mortality of weaned pigs with Streptococcus suis with the use of in-water potassium penicillin G.

This study evaluated the efficacy of potassium penicillin G in drinking water of weaned pigs to reduce mortality and spread of infection caused by Streptococcus suis. A total of 896 18-day-old weaned pigs were randomly assigned to either treatment with potassium penicillin G in-water (Treated), or no treatment (Control). The outcomes analyzed were total mortality, mortality due to S. suis, and overall counts of S. suis colonies. The risk of mortality due to S. suis and total mortality were significantly increased in the Control group compared with Treated pigs (P < 0.05). Bacterial culture of posterior pharyngeal swabs indicated that Control pigs were significantly more likely to have ≥ 1000 colonies of S. suis per plate than were Treated pigs (P < 0.05). This study demonstrates that potassium penicillin G administered in drinking water is effective in reducing mortality associated with S. suis infection and reducing tonsillar carriage of S. suis.

When infections collide--gummatous syphilis in an HIV-infected individual.

Syphilis and HIV are both transmitted sexually and have emerged as important co-pathogens with reciprocal augmentation in transmission and disease progression. HIV-positive patients tend to experience more aggressive symptomatology due to syphilis and are at greater risk of developing neurological disease. Similarly, standard therapy for syphilis may be inadequate in HIV-positive individual suggesting intensified treatment regimens may be required along with close follow-up. We report here the case of a 50-year-old HIV-positive male presenting with an unusual constellation of neurological findings. Although he had been treated appropriately 10 years previously for primary syphilis, investigations revealed multiple current intracranial gummas. Treatment with high-dose intravenous penicillin G resulted in clinical and radiographic resolution. Given the broad differential for HIV-positive patients presenting with neurological symptoms, the clinician must maintain a high index of suspicion for syphilis known for its varied and at times unusual manifestations. Further, prior treatment of syphilis does not ensure cure and so syphilis must be considered irrespective of treatment history.

Management of tolerance induction in patients with suspected penicillin allergy--a case study.

BACKGROUND: In some diseases penicillin is the treatment of choice. Case studies have shown a good response for the treatment of circumscribed scleroderma or scleroderma adultorum of Buschke. A suspected allergy to penicillin in a patient's history may limit this helpful therapy option. Allergy testing is often inconclusive. If indicated, tolerance induction leading to therapy with penicillin can be carried out. PATIENTS AND METHODS: We present two patients with circumscribed sclerosis and scleredema Buschke, who had a suspected allergy to penicillin. Due to limited therapy options and in insufficient response to other therapeutics, the decision for a tolerance induction with penicillin was made. Penicillin was successfully administered by following a scheme of tolerance induction starting with oral doses and ending with high doses of intravenous penicillin G. RESULTS: In both cases, penicillin G, administered over a period of three weeks, was well tolerated up to the high dose of 3 x 10 Mega IU/day. Substantial clinical improvement was achieved in all cases without any complications. CONCLUSION: This case study demonstrates that a suspected allergy to penicillin does not preclude an eventual treatment with this valuable drug. Allergy testing should routinely be carried out first. If suspicion of an allergy persists, tolerance induction can be attempted according to the new scheme described here. Starting with a careful, initial oral dose regimen, treatment can be continued with an increasing intravenous dose followed by maintenance therapy with high-dose penicillin G. It should be clear that this policy is only restricted for patients who are at risk for a hypersensitivity to penicillin, i.e., because of a clinical manifested incompatibility in the past.

Nodular morphea.

Scleroderma may present as being strictly limited to the skin, as in morphea, or within a multiorgan disease, as in systemic sclerosis. Accordingly, cutaneous manifestations vary clinically. In nodular or keloidal scleroderma, patients develop lesions that are clinically indistinguishable from a keloid; however, the histopathological findings are more variable. We describe a 16-year-old girl with morpheic lesions for 3-4 years and additional development of keloidal nodules within these lesions. The histological examination revealed a hypertrophic scar besides morphea.

Influence of antibiotic therapy on serum levels of reactive oxygen species in ovariectomized bitches.

This study was conducted on 60 ovariectomized bitches. The objectives were to measure the mean reactive oxygen species (ROS) concentrations before, during and after surgery, and to investigate the effect of the administration of five different antibiotic treatments: amoxicillin, benzylpenicillin/dihydrostreptomycin, sulfametazine/sulfamerazine/sulfathiazole, enrofloxacin, lincomycin/spectinomycin. The first value recorded represented the mean ROS concentration in anestral bitches and constitutes a reference level with which to compare the subsequent measurements. After premedication, induction of anesthesia and during maintenance and surgery, ROS serum concentrations showed constant values until the end of surgery. After surgery and during antibiotic administration, an increase in ROS concentration occurred, which differed among the five groups in relation to the antibiotics employed. The lowest increases occurred in the groups treated with the combination of lincomycin/spectinomycin, and with amoxicillin; whereas the highest increases were detected in the group treated with enrofloxacin. The three other antibiotics showed an intermediate level of influence on oxidative status.

Comparative treatment of alpha-amanitin poisoning with N-acetylcysteine, benzylpenicillin, cimetidine, thioctic acid, and silybin in a murine model.

STUDY OBJECTIVE: The foraging of wild mushrooms can be complicated by toxicity from several mushroom types. Amatoxin, a peptide contained in several mushroom species, accounts for the majority of severe mushroom poisonings by binding to RNA polymerase II irreversibly, leading to severe hepatonecrosis. There is no effective antidote for severe amatoxin poisoning. We compare the effectiveness of 5 potential antidotal therapies in limiting the degree of hepatonecrosis in a randomized, controlled, murine model of amatoxin-induced hepatotoxicity. METHODS: One hundred eighty male Institute of Cancer Research mice were randomized into 6 equal groups. Within each group, 21 mice were intraperitoneally injected with 0.6 mg/kg of alpha-amanitin (amatoxin); the remaining 9 were injected with 0.9% normal saline solution. Four hours postinjection, each group of 30 mice was randomized to 1 of 5 intraperitoneal treatments (N-acetylcysteine, benzylpenicillin, cimetidine, thioctic acid, or silybin) or normal saline solution. Repeated dosing was administered intraperitoneally every 4 to 6 hours for 48 hours. After 48 hours of treatment, each subject was killed, cardiac blood was aspirated for hepatic aminotransferase measurements (alanine transaminase and aspartate transaminase), and liver specimens were harvested to evaluate the extent of hepatonecrosis. The degree of hepatonecrosis was determined by a pathologist blinded to the treatment group and divided into 5 categories according to percentage of hepatonecrosis. RESULTS: Amanitin significantly increased aspartate transaminase in treated mice compared with normal saline solution-treated controls (mean [SD] 2,441 [2,818] IU/L versus 310 [252]; P=.03). None of the antidotal therapies were found to significantly decrease the increase in aminotransferases compared with controls. Further, none of the antidotal therapies demonstrated an important decrease in hepatonecrosis compared with controls when a histologic grading scale was used. CONCLUSION: In this murine model, N-acetylcysteine, benzylpenicillin, cimetidine, thioctic acid, and silybin were not effective in limiting hepatic injury after alpha-amanitin poisoning. Increases of aminotransferases and degrees of histologic hepatonecrosis were not attenuated by these antidotal therapies.

Actinomycosis: a differential diagnosis for appendicitis. A case report and review of the literature.

Actinomyces is a genus of gram-positive anaerobic or microaerophilic bacteria that colonize the upper respiratory and gastrointestinal tracts and the female genital tract. These organisms cause disseminated disease in the mouth, the respiratory system, and rarely in the gastrointestinal tract. The diseases produced by Actinomyces species result from the disruption of the barriers that allow the dissemination of the bacteria through the surrounding tissues. The appendix is often a nidus of Actinomyces infection, but a prompt diagnosis cannot be made without the results of histologic examination of the appendix. The treatment of choice for actinomycosis of the appendix is the high-dose parenteral administration of penicillin G for 2 weeks immediately after the diagnosis has been made and continued oral treatment with that agent for at least the next 6 months. We present the case of a 13-year-old adolescent boy with actinomycosis of the appendix that was identified by histologic examination after appendectomy.

Continuous-infusion penicillin home-based therapy for serious infections due to penicillin-susceptible pathogens.

To evaluate the feasibility of continuous-infusion (CI) penicillin in the treatment of serious bacterial infections, consecutive adult patients with deep-seated infections due to penicillin-susceptible pathogens were treated with CI aqueous penicillin G in a home-based programme, and their treatment outcomes were reviewed. Thirty-one patients with microbiologically proven infections completed the planned course of treatment. Twenty of 31 (65%) were followed for at least 2 months thereafter, and all remained free of relapse. One patient had fever attributable to penicillin hypersensitivity, two patients developed catheter-site infections and one patient developed catheter-related bacteraemia. Thus, CI penicillin is feasible for the home-based treatment of a variety of deep-seated infections with minimal toxicity.