Distinct contribution of hyperbaric oxygen therapy to human neutrophil function and antibiotic efficacy against Staphylococcus aureus.

Staphylococcus aureus (SA) causes superficial and severe endovascular infections. The present in vitro study investigates the anti-SA mechanisms of hyperbaric oxygen therapy (HBOT) on direct bacterial killing, antibiotic potentiation, and polymorphonuclear leukocyte (PMN) enhancement. SA was exposed to isolated human PMNs, tobramycin, ciprofloxacin, or benzylpenicillin. HBOT was used as one 90-min session. Bacterial survival was evaluated after 4 h by quantitative bacteriology. PMN functionality as reactive oxygen species (ROS) production was measured by means of dihydrorhodamine 123 analysis. We showed that HBOT exhibits significant direct anti-SA effects. HBOT increased the anti-SA effects of PMNs by 18% after PMA stimulation (p = 0.0004) and by 15% in response to SA (p = 0.36). HBOT showed an additive effect as growth reductions of 26% to sub-MICs of tobramycin (p = 0.0057), 44% to sub-MICs of ciprofloxacin (p = 0.0001), and 26% to sub-MICs of penicillin (p = 0.038). The present in vitro study provides evidence that HBOT has differential mechanisms mediating its anti-SA effects. Our observation supports the clinical possibility for adjunctive HBOT to augment the host immune response and optimize the efficacy of antibiotic treatments.

Co-administration of a Rhododendron tomentosum extract does not affect mercury tissue concentrations and excretion rate in methylmercury-treated adult male rats.

OBJECTIVES: Consumption of fish/seafood is clearly linked to higher mercury levels in human tissue samples. However, correlations between methylmercury (MeHg) intakes calculated from dietary surveys and mercury body burdens are usually weak and can vary across populations. Different factors may affect MeHg absorption, distribution, metabolism and excretion, including co-exposures to phytochemicals and antibiotics, which were shown to affect mercury body burdens in rodents. Based on the observation that rat pups developmentally exposed to MeHg and a Rhododendron tomentosum extract (Labrador Tea) presented significantly higher blood mercury levels at weaning compared to pups exposed to MeHg alone, the modulation of MeHg toxicokinetics by Labrador Tea was further investigated in adult rats. RESULTS: Total mercury levels were quantified in the blood, liver, kidney and feces of adult male rats exposed to MeHg (1.2 mg/kg bodyweight/day, for 3 weeks) administered either alone or in combination with Labrador Tea (100 mg/kg bodyweight/day) or with an antibiotics cocktail (to inhibit MeHg demethylation by gut bacteria). While the reduced fecal excretion and higher blood mercury levels expected from antibiotics-treated rats were observed, mercury levels in samples from Labrador Tea-treated rats were not significantly different from those measured in samples from rats exposed to MeHg alone.

Pollen reverses decreased lifespan, altered nutritional metabolism and suppressed immunity in honey bees (Apis mellifera) treated with antibiotics.

Nutrition is involved in regulating multiple aspects of honey bee biology such as caste, immunity, lifespan, growth and behavioral development. Deformed wing virus (DWV) is a major pathogenic factor which threatens honey bee populations, and its replication is regulated by the nutrition status and immune response of honey bees. The alimentary canal of the honey bee is home to a diverse microbial community that provides essential nutrients and serves to bolster immune responses. However, to what extent gut bacteria affect honey bee nutrition metabolism and immunity with respect to DWV has not been investigated fully. In this study, newly emerged worker bees were subjected to four diets that contained (1) pollen, (2) pollen and antibiotics, (3) neither pollen nor antibiotics or (4) antibiotics alone. The expression level of two nutrition genes target of rapamycin (tor) and insulin like peptide (ilp1), one nutritional marker gene vitellogenin (vg), five major royal jellyprotein genes (mrjp1-5), one antimicrobial peptide regulating gene relish (rel), and DWV virus titer and its replication intermediate, negative RNA strand, were determined by qRT-PCR from the honey bees at 7 days post-antibiotic treatment. Additionally, honey bee head mass and survival rate were measured. We observed that antibiotics decreased the expression of tor and rel, and increased DWV titer and its replication activity. Expression of ilp1, mrjp1-5 and vg, and honey bee head mass were also reduced compared with bees on a pollen diet. Antibiotics also caused a significant drop in survivorship, which could be rescued by addition of pollen to the diet. Of importance, pollen could partially rescue the loss of vg and mrjp2 while also increasing the head mass of antibiotic-treated bees. Our results illuminate the roles of bacteria in honey bee nutrition, metabolism and immunity, which confer the ability to inhibit virus replication, extend honey bee lifespan and improve overall health.

A fast and simple FIA-chemiluminescence method for the evaluation of Roselle flowers as scavenger of the free radicals generated by UV irradiated antibiotics.

This work proposes a new method for the in vitro evaluation of the effect of UV irradiation on the production of free radicals and other reactive species during the photodecomposition of drugs. The method was based on the UV irradiation of antibiotics molecules to generate excited states that undergo to homolytic bond cleavages. These reactive species can be detected by their ability to oxidize the luminol, producing the electronically excited aminophtalate, which decays to the ground state releasing electromagnetic radiation in the visible zone of the spectrum. This method was applied to penicillin G, nafcillin, azlocillin and neomycin dissolved in water. It was found that the intensity of the luminol chemiluminescence emission (CL) was proportional to the concentration and dependent on the molecular structure of these drugs. Under the optimized conditions, it was found that penicillin and azlocillin were the most susceptible to photodegradation, while neomycin sulfate was the less affected by the UV light. It was observed that the addition to the antibiotics dissolutions of a hydro-alcoholic extract of petals of calyxes of Roselle reduced the CL intensity, indicating that the extract was able to scavenge the free radicals in the irradiated drugs. This result suggest that its addition to the antibiotics can help in the protection against the radicals formed during the exposition to solar light of patients treated with topic similar antibiotics.

Back to the Future: Penicillin-Susceptible Staphylococcus aureus.

BACKGROUND: Widespread penicillin usage rapidly resulted in the emergence of penicillin resistance in Staphylococcus aureus. However, new data suggest that penicillin susceptibility may be in a period of renaissance. The objective of our study was to quantify penicillin resistance in methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. METHODS: We retrospectively reviewed all adult MSSA bacteremia from April 2010 to April 2015 at the McGill University Health Centre (Montreal, QC, Canada). Susceptibility to penicillin, erythromycin, clindamycin, and trimethoprim-sulfamethoxazole (TMP-SMX) was determined in accordance with the Clinical & Laboratory Standards Institute guidelines. RESULTS: There were 324 unique episodes of MSSA bacteremia. Ninety (28%) isolates were susceptible to penicillin, 229 (71%) to erythromycin, 239 (74%) to clindamycin, and 317 (98%) to TMP-SMX. Isolates that were penicillin resistant were more likely to also be resistant to other antibiotics, but a statistically significant association was apparent only for erythromycin resistance (76/234, 32.2% vs 19/90, 21.1%, P = .04). The median age of patients was 67.5 years (interquartile range 52-78) and overall in-hospital 30-day mortality was 16.3% (53 deaths). After adjustment for patient age, there was no association between penicillin resistance and either intensive care unit admission or death. CONCLUSION: More than one-quarter of patients with MSSA bacteremia potentially could be treated with parenteral penicillin, which may offer pharmacokinetic advantages over other beta-lactam drugs and potentially improved outcomes.

Two case reports of the successful eradication of new isolates of Burkholderia cepacia complex in children with cystic fibrosis.

BACKGROUND: Chronic infection with Burkholderia cepacia complex (BCC) has a detrimental effect on morbidity and mortality for patients with cystic fibrosis (CF). It is therefore logical to attempt to eradicate new isolates however there is a paucity of information to guide treatment. We report the successful eradication of new isolates of BCC in two children with CF. CASE PRESENTATION: Burkholderia cepacia was successfully eradicated in a 14 year old boy with CF and Burkholderia gladioli was successfully eradicated in a six year old girl with CF. In both children two weeks of intravenous (IV) tobramycin, ceftazidime and temocillin were used followed by three months of inhaled tobramycin. Bronchoalveolar lavage samples taken during flexible bronchoscopy were used prior to treatment to exclude spontaneous clearance as well as after treatment to confirm eradication. CONCLUSIONS: New isolates of BCC can be successfully eradicated in children with CF. More research is urgently required in this area to identify the best treatment regimen for BCC eradication.

A microplate assay for the coupled transglycosylase-transpeptidase activity of the penicillin binding proteins; a vancomycin-neutralizing tripeptide combination prevents penicillin inhibition of peptidoglycan synthesis.

A microplate, scintillation proximity assay to measure the coupled transglycosylase-transpeptidase activity of the penicillin binding proteins in Escherichia coli membranes was developed. Membranes were incubated with the two peptidoglycan sugar precursors UDP-N-acetyl muramylpentapeptide (UDP-MurNAc(pp)) and UDP-[(3)H]N-acetylglucosamine in the presence of 40 µM vancomycin to allow in situ accumulation of lipid II. In a second step, vancomycin inhibition was relieved by addition of a tripeptide (Lys-D-ala-D-ala) or UDP-MurNAc(pp), resulting in conversion of lipid II to cross-linked peptidoglycan. Inhibitors of the transglycosylase or transpeptidase were added at step 2. Moenomycin, a transglycosylase inhibitor, had an IC50 of 8 nM. Vancomycin and nisin also inhibited the assay. Surprisingly, the transpeptidase inhibitors penicillin and ampicillin showed no inhibition. In a pathway assay of peptidoglycan synthesis, starting from the UDP linked sugar precursors, inhibition by penicillin was reversed by a 'neutral' combination of vancomycin plus tripeptide, suggesting an interaction thus far unreported.

Simplified antibiotic regimens for the management of clinically diagnosed severe infections in newborns and young infants in first-level facilities in Karachi, Pakistan: study design for an outpatient randomized controlled equivalence trial.

BACKGROUND: Infection in young infants is a major cause of morbidity and mortality in low-middle income countries, with high neonatal mortality rates. Timely case management is lifesaving, but the current standard of hospitalization for parenteral antibiotic therapy is not always feasible. Alternative, simpler antibiotic regimens that could be used in outpatient settings have the potential to save thousands of lives. METHODS: This trial aims to determine whether 2 simplified antibiotic regimens are equivalent to the reference therapy with 7 days of once-daily (OD) intramuscular (IM) procaine penicillin and gentamicin for outpatient management of young infants with clinically presumed systemic bacterial infection treated in primary health-care clinics in 5 communities in Karachi, Pakistan. The reference regimen is close to the current recommendation of the hospital-based intravenous ampicillin and gentamicin therapy for neonatal sepsis. The 2 comparison arms are (1) IM gentamicin OD and oral amoxicillin twice daily for 7 days; and (2) IM penicillin and gentamicin OD for 2 days, followed by oral amoxicillin twice daily for 5 days; 2250 "evaluable" infants will be enrolled. The primary outcome of this trial is treatment failure (death, deterioration or lack of improvement) within 7 days of enrollment. Results are expected by early 2014. DISCUSSION: This trial will determine whether simplified antibiotic regimens with fewer injections in combination with high-dose amoxicillin are equivalent to 7 days of IM procaine penicillin and gentamicin in young infants with clinical severe infection. Results will have program and policy implications in countries with limited access to hospital care and high burden of neonatal deaths.

The involvement of iNOS activity in the anticonvulsant effect of grape seed extract on the penicillin-induced epileptiform activity in rats.

Grape seed extract (GSE) has been known as being neuroprotective due to its antioxidant properties. The aim of the present study was to examine both the effect of GSE on the penicillin-induced epileptiform activity in rat and the role of nitric oxide (NO) pathway in the effect of GSE. GSE, at doses of 50, 100, 200 mg/kg, significantly decreased the mean frequency of epileptiform activity. GSE, at the highest dose (400 mg/kg), did not change either the frequency or amplitude of epileptiform activity. GSE, at a dose of 200 mg/kg, was the most effective in changing the frequency of epileptiform activity. The occurrence of anticonvulsant activity of GSE was significantly delayed in the presence of selective inducible nitric oxide synthase (iNOS) inhibitor, aminoguanidine (60 mg/kg), which was inhibited by the NO precursor, L-arginine (500 mg/kg). The administration of a non-selective NOS inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) partially reversed the anticonvulsant activity of GSE. Selective neuronal nitric oxide synthase (nNOS) inhibitor, 7-nitroindazole (7-NI) and L-arginine showed a similar anticonvulsant activity in the presence of GSE. The electrophysiological evidence of the present study indicates that GSE decreases the mean frequency of penicillin-induced epileptiform activity, suggesting an anticonvulsant role. iNOS/NO pathway could be involved in mediating anticonvulsant effect of GSE on the epileptiform activity.

Microbiological analysis of a prospective, randomized, double-blind trial comparing moxifloxacin and clindamycin in the treatment of odontogenic infiltrates and abscesses.

The objective of this study was to identify the oral pathogens found in odontogenic infections, to determine their susceptibilities to amoxicillin-clavulanic acid (AMC), clindamycin (CLI), doxycycline (DOX), levofloxacin (LVX), moxifloxacin (MXF), and penicillin (PEN), and to search for associations between specific pathogens and types of infection. Swabs from patients enrolled in a randomized, double-blind phase II trial comparing MXF with CLI for the treatment of odontogenic abscesses or inflammatory infiltrates were cultured on media for aerobes and anaerobes. All bacterial isolates were identified at the species level. Overall, 205 isolates were cultured from 71 patients: 77 viridans group streptococci, 56 Prevotella spp., 19 Neisseria spp., 17 Streptococcus anginosus group isolates and hemolytic streptococci, 15 other anaerobes, and 21 other bacteria. Ninety-eight percent of pathogens were susceptible to MXF, 96% to AMC, 85% to LVX, 67% to PEN, 60% to CLI, and 50% to DOX. S. anginosus group and hemolytic streptococci were found significantly more frequently (P = 0.04) in patients with abscesses (12/95) than in patients with infiltrates (5/110). In four patients with infiltrates who failed to respond to CLI therapy, three isolates of the Streptococcus mitis group and four Neisseria spp. resistant to CLI were found. In this study, S. anginosus group and hemolytic streptococci were clearly associated with odontogenic abscesses. Our analysis suggests that viridans group streptococci and Neisseria spp. play a decisive role in the etiology of odontogenic infiltrates. The high in vitro activity of MXF against odontogenic bacteria corresponds well to its clinical results in the treatment of odontogenic abscesses and infiltrates.

Leptospirosis-associated acute kidney injury: penicillin at the late stage is still controversial.

WHAT IS KNOWN AND OBJECTIVE: Some antimicrobial agents are active in vitro against Leptospiras. The use of penicillins at the late stage of leptospirosis is still controversial. We aimed to evaluate the use of penicillin in patients with leptospirosis-associated acute kidney injury (AKI). METHODS: A retrospective study was conducted of patients with leptospirosis admitted to two hospitals in Fortaleza city, Brazil, between 1985 and 2008. AKI was defined according to the RIFLE and AKIN classifications. Patients were divided in two groups according to whether they were treated with a penicillin or not. RESULTS: Two hundred and eighty-seven patients were included, with an average age of 36·8±15·6 years and mostly male (80·8%). One hundred and twelve patients (39%) received a penicillin. Patients treated with a penicillin were younger (32±14 years vs. 39±16 years, P=0·0002) and had a shorter hospital stay (8·4±5·0 vs. 11±7·7 days, P<0·0001). There was no difference in the onset of symptoms before hospital admission between the two groups (6·5±3·0 vs. 7·7±4·7, P=0·33). Systolic blood pressure was lower in the penicillin group (111±21 vs. 119±22 mmHg, P=0·04). AKI, need of dialysis and renal recovery at the time of hospital discharge were more frequent in patients who did not use a penicillin (P<0·05). Mortality was similar in both groups (11·6% vs. 13·7%, P=0·60). CONCLUSION: Treatment of leptospirosis with antibiotics, including the penicillin, remains controversial. The main benefit of using penicillin in the present study was a reduction in the length of hospital stay and fewer complications, such as AKI, but its use was not associated with a decrease in mortality. On balance of risks and benefits, we recommend the use of penicillin in late-stage leptospirosis.

Novel mutations in a patient isolate of Streptococcus agalactiae with reduced penicillin susceptibility emerging after long-term oral suppressive therapy.

Penicillin nonsusceptibility has been demonstrated in group B streptococci (GBS), but there is limited information regarding mechanisms of resistance. We report a case of GBS with reduced susceptibility to penicillin emerging after long-term suppressive oral penicillin therapy for a prosthetic joint infection. Molecular characterization of the isolate before and after long-term penicillin therapy revealed 5 mutations in the ligand-binding regions of PBP1a, -2a, and -2x not previously reported in GBS.

Barriers to intravenous penicillin use for treatment of nonmeningitis pneumococcal disease.

Infectious disease physicians were surveyed to determine whether the new penicillin breakpoint change will translate into increased penicillin use and to identify barriers to intravenous (i.v.) penicillin use for pneumococcal infections. The inconvenience of i.v. penicillin may limit its use despite a reduction in numbers of infections considered resistant.

Aspectos da admissão e evolução de crianças hospitalizadas com suspeita de pneumonia adquirida na comunidade em Salvador / Aspects of admission and outcome of children hospitalized with suspected community-acquired pneumonia in Salvador

A pneumonia na infância permanece um assunto relevante, tendo em vista a sua elevada taxa de mortalidade mundial, principalmente nos países em desenvolvimento. Objetivo: Descrever o resultado da hospitalização de crianças internadas com suspeita diagnostica de pneumonia. Desenho do estudo: Coorte retrospectiva. Material e métodos: Foi realizado acompanhamento retrospectivo de pacientes internados com suspeita de pneumonia em um centro pediátrico, de outubro de 2002 a outubro de 2005. A partir dos prontuários médicos, dados demográficos, de história clínica, do exame físico, do tratamento, da evolução e do desfecho foram coletados e registrados em formulário específico para o estudo. Todos os casos incluídos tiveram as radiografias de tórax avaliadas por radiologista cego às informações clínicas, com o objetivo de definir a presença ou não de infiltrado pulmonar e avaliar a presença de alterações radiológicas outras. A população do estudo foi alocada -“m quatro grupos diferente? para que pudessem ter suas variáveis comparadas entre pacientes com características semelhantes. Resultados: No grupo das crianças > 2 meses de idade, internadas com diagnóstico clínico-radiológico de pneumonia e tratadas com penicilina cristalina, as freqüências de febre (46,4% vs. 26,3%, /’=0,002), taquipnéia (73,6% vs. 59,4%,

Colitis and gastroparesis associated with syphilis in an HIV-infected person with an undetectable viral load.

We present a patient with fully controlled HIV disease and a normal CD4 count whose initial treatment for syphilis failed. Biopsy-proven syphilitic colitis and severe gastroparesis developed, requiring the insertion of a temporary percutaneous gastrostomy tube. The patient responded to a course of high-dose aqueous crystalline penicillin followed by doxycycline, and he completely recovered. The occurrence of failure of conventional syphilis treatment in HIV-infected patients is discussed.

Is oral penicillin an effective chemoprophylaxis against leptospirosis? A placebo controlled field study in the Kandy District, Sri Lanka.

Leptospirosis poses a severe threat to the lives of farmers in Sri Lanka, thus, development of an effective chemoprophylaxis is deemed essential. We tested oral penicillin as chemoprophylaxis against leptospirosis in high transmission areas in central Sri Lanka in October 2005. Eight hundred active farmers were randomly assigned to take either oral penicillin (500 mg bid) or a similar looking placebo over a month during active farming season. The primary study point was the incidence of serologically confirmed leptospirosis. Data were available for 602 subjects of whom 319 (152 taking penicillin and 167 taking placebo) had good compliance, shown by tablet count. Of 5 subjects hospitalized with fever, 3 had serological evidence of leptospirosis, all of whom belonged to the placebo group. Therefore, oral penicillin may be effective chemoprophylaxis against leptospirosis.

[Treatment of community-acquired pneumonia--treatment]. / Samfundserhvervet pneumoni--behandling.

Penicillin is the drug of choice for treatment of community-acquired pneumonia (CAP) in Denmark. The primary determinant for therapeutic activity of penicillin is ''penicillin time'' (T>MIC), i.e. time with penicillin concentration above minimum inhibitory concentration. Eradication of S. pneumoniae requires T>MIC above 40-50%. The second determinant for therapeutic activity is the ratio between maximum penicillin concentration in serum and MIC (Cmax/MIC). Considering penicillin pharmacokinetics, intravenous penicillin 2 million units four times a day is recommended as empirical treatment of CAP.

Análisis del consumo de antibióticos en la población pediátrica de Castilla y León durante el período 2001 a 2005 / Analysis of antibiotic consumption in the pediatric population of Castile and León (Spain) from 2001 to 2005

Objetivos. Analizar la evolución de la utilización de antibióticos en la población pediátrica, durante los últimos 5 años en la Comunidad Autónoma de Castilla y León. Material y métodos. Se procesaron los antibióticos prescritos a la población pediátrica en el ámbito extrahospitalario, utilizando la base de datos CONCYLIA. La unidad técnica de medida fue la dosis diaria definida (DDD) y el indicador comparativo utilizado la DDD por 1.000 habitantes por día (DHD). Resultados. El consumo global fue elevado (21,21 DHD). A lo largo de los 5 años estudiados se observaron variaciones importantes, especialmente en el año 2003 en que se alcanzó el mayor consumo (25,05 DHD). Los subgrupos terapéuticos más prescritos fueron las penicilinas de amplio espectro (8,08 DHD) y penicilinas asociadas a inhibidores de la betalactamasa (7,29 DHD), seguidas a mayor distancia por cefalosporinas (2,81 DHD) y macrólidos (2,52 DHD). El porcentaje de prescripción de penicilinas de amplio espectro fue más elevado que el de penicilinas asociada a inhibidores de la betalactamasa durante los años 2001 y 2002, se igualó en el 2003 y se invirtió esta tendencia los últimos 2 años. Conclusiones. Las diferencias de consumo fueron notables a lo largo del tiempo. Se observó un cambio en el patrón de uso, principalmente a favor de las penicilinas asociadas a inhibidores de la betalactamasa los últimos 2 años

Objectives. To analyze trends in antibiotic use among the pediatric population of Castile and León from 2001 to 2005. Material and methods. The antibiotics prescribed to the pediatric population in primary care were processed using the CONCYLIA database. The technical unit of measurement was the defined daily dose (DDD) and the comparative indicator used was the DDD per 1000 inhabitants/day (DID). Results. Overall consumption was high (21.21 DID). Throughout the 5 years of the study we observed substantial variations, especially in 2005, the year in which consumption was highest (25.05 DID). The therapeutic subgroups most frequently prescribed were wide-spectrum penicillins (8.08 DID) and penicillins associated with beta-lactamase inhibitors (7.29 DID), followed by cephalosporins (2.81 DHD) and macrolides (2.52 DHD). The percentage of wide-spectrum penicillin prescription was higher than that of penicillins associated with beta-lactamase inhibitors between 2001 and 2002. These percentages were similar in 2003, and the percentage of wide-spectrum penicillin prescription was lower than that of penicillins associated with beta-lactamase inhibitors in the last 2 years of the study. Conclusions. Marked differences in consumption were observed over the study period. Changes in patterns of use were found, with an increase in the use of penicillins associated with beta-lactamase inhibitors in the last 2 years of the study

[Surgical correction of scleroderma en coup de sabre]. / Operative Korrektur einer Sklerodermie en coup de sabre durch En-bloc-Resektion.

A 15-year-old patient developed scleroderma en coup de sabre on right temple at 5 years of age. Multiple treatments (3 cycles of intravenous penicillin, topical glucocorticosteroids, topical calcipotriol, and cream PUVA phototherapy combined with topical calcipotriol) produced no improvement. The patient suffered greatly from the psychosocial stigmatization, so that the entire lesion was resected at 14 years of age. One year after the operation a thin non-sclerotic scar was present; tiny lateral areas of sclerosis not included in the operative field were unchanged. The operation greatly improved the patient's daily life. The surgical therapy of scleroderma en coup de sabre offers an interesting therapeutic alternative.