Showing papers on "Penicillin published in 2013"

Antibiotics for community-acquired pneumonia in children.

Abstract: Background Pneumonia caused by bacterial pathogens is the leading cause of mortality in children in low-income countries. Early administration of antibiotics improves outcomes. Objectives To identify effective antibiotic drug therapies for community-acquired pneumonia (CAP) of varying severity in children by comparing various antibiotics. Search methods We searched CENTRAL 2012, Issue 10; MEDLINE (1966 to October week 4, 2012); EMBASE (1990 to November 2012); CINAHL (2009 to November 2012); Web of Science (2009 to November 2012) and LILACS (2009 to November 2012). Selection criteria Randomised controlled trials (RCTs) in children of either sex, comparing at least two antibiotics for CAP within hospital or ambulatory (outpatient) settings. Data collection and analysis Two review authors independently extracted data from the full articles of selected studies. Main results We included 29 trials, which enrolled 14,188 children, comparing multiple antibiotics. None compared antibiotics with placebo. Assessment of quality of study revealed that 5 out of 29 studies were double-blind and allocation concealment was adequate. Another 12 studies were unblinded but had adequate allocation concealment, classifying them as good quality studies. There was more than one study comparing co-trimoxazole with amoxycillin, oral amoxycillin with injectable penicillin/ampicillin and chloramphenicol with ampicillin/penicillin and studies were of good quality, suggesting the evidence for these comparisons was of high quality compared to other comparisons. In ambulatory settings, for treatment of World Health Organization (WHO) defined non-severe CAP, amoxycillin compared with co-trimoxazole had similar failure rates (odds ratio (OR) 1.18, 95% confidence interval (CI) 0.91 to 1.51) and cure rates (OR 1.03, 95% CI 0.56 to 1.89). Three studies involved 3952 children. In children with severe pneumonia without hypoxaemia, oral antibiotics (amoxycillin/co-trimoxazole) compared with injectable penicillin had similar failure rates (OR 0.84, 95% CI 0.56 to 1.24), hospitalisation rates (OR 1.13, 95% CI 0.38 to 3.34) and relapse rates (OR 1.28, 95% CI 0.34 to 4.82). Six studies involved 4331 children below 18 years of age. In very severe CAP, death rates were higher in children receiving chloramphenicol compared to those receiving penicillin/ampicillin plus gentamicin (OR 1.25, 95% CI 0.76 to 2.07). One study involved 1116 children. Authors' conclusions For treatment of patients with CAP in ambulatory settings, amoxycillin is an alternative to co-trimoxazole. With limited data on other antibiotics, co-amoxyclavulanic acid and cefpodoxime may be alternative second-line drugs. Children with severe pneumonia without hypoxaemia can be treated with oral amoxycillin in an ambulatory setting. For children hospitalised with severe and very severe CAP, penicillin/ampicillin plus gentamycin is superior to chloramphenicol. The other alternative drugs for such patients are co-amoxyclavulanic acid and cefuroxime. Until more studies are available, these can be used as second-line therapies. There is a need for more studies with radiographically confirmed pneumonia in larger patient populations and similar methodologies to compare newer antibiotics. Recommendations in this review are applicable to countries with high case fatalities due to pneumonia in children without underlying morbidities and where point of care tests for identification of aetiological agents for pneumonia are not available.

Community-acquired neonatal and infant sepsis in developing countries: efficacy of WHO's currently recommended antibiotics—systematic review and meta-analysis

Abstract: Objective To review the aetiology and antibiotic resistance patterns of community-acquired sepsis in developing countries in infants where no clear focus of infection is clinically identified. To estimate the likely efficacy of WHO9s recommended treatment for infant sepsis. Design A systematic review of the literature describing the aetiology of community-acquired neonatal and infant sepsis in developing countries. Using meta-analytical methods, susceptibility was determined to the antibiotic combinations recommended by WHO: (1) benzylpenicillin/ampicillin and gentamicin, (2) chloramphenicol and benzylpenicillin, and (3) third-generation cephalosporins. Results 19 studies were identified from 13 countries, with over 4000 blood culture isolates. Among neonates, Staphylococcus aureus , Klebsiella spp. and Escherichia coli accounted for 55% (39–70%) of culture positive sepsis on weighted prevalence. In infants outside the neonatal period, the most prevalent pathogens were S aureus , E coli , Klebsiella spp., Streptococcus pneumoniae and Salmonella spp., which accounted for 59% (26–92%) of culture positive sepsis. For neonates, penicillin/gentamicin had comparable in vitro coverage to third-generation cephalosporins (57% vs 56%). In older infants (1–12 months), in vitro susceptibility to penicillin/gentamicin, chloramphenicol/penicillin and third-generation cephalosporins was 63%, 47% and 64%, respectively. Conclusions The high rate of community-acquired resistant sepsis—especially that caused by Klebsiella spp. and S aureus —is a serious global public health concern. In vitro susceptibility data suggest that third-generation cephalosporins are not more effective in treating sepsis than the currently recommended antibiotics, benzylpenicillin and gentamicin; however, with either regimen a significant proportion of bacteraemia is not covered. Revised recommendations for effective second-line antibiotics in neonatal and infant sepsis in developing countries are urgently needed.

Penicillin to Prevent Recurrent Leg Cellulitis

Abstract: We conducted a double-blind, randomized, controlled trial involving patients with two or more episodes of cellulitis of the leg who were recruited in 28 hospitals in the United Kingdom and Ireland. Randomization was performed according to a computer-generated code, and study medications (penicillin [250 mg twice a day] or placebo for 12 months) were dispensed by a central pharmacy. The primary outcome was the time to a first recurrence. Participants were followed for up to 3 years. Because the risk of recurrence was not constant over the 3-year period, the primary hypothesis was tested during prophylaxis only. Results A total of 274 patients were recruited. Baseline characteristics were similar in the two groups. The median time to a first recurrence of cellulitis was 626 days in the penicillin group and 532 days in the placebo group. During the prophylaxis phase, 30 of 136 participants in the penicillin group (22%) had a recurrence, as compared with 51 of 138 participants in the placebo group (37%) (hazard ratio, 0.55; 95% confidence interval [CI], 0.35 to 0.86; P = 0.01), yielding a number needed to treat to prevent one recurrent cellulitis episode of 5 (95% CI, 4 to 9). During the no-intervention follow-up period, there was no difference between groups in the rate of a first recurrence (27% in both groups). Overall, participants in the penicillin group had fewer repeat episodes than those in the placebo group (119 vs. 164, P = 0.02 for trend). There was no significant between-group difference in the number of participants with adverse events (37 in the penicillin group and 48 in the placebo group, P = 0.50). Conclusions In patients with recurrent cellulitis of the leg, penicillin was effective in preventing subsequent attacks during prophylaxis, but the protective effect diminished progressively once drug therapy was stopped. (Funded by Action Medical Research; PATCH I Controlled-Trials.com number, ISRCTN34716921.)

The impact of penicillin skin testing on clinical practice and antimicrobial stewardship

Abstract: BACKGROUND Penicillin skin testing (PST) is a simple and reliable way of diagnosing penicillin allergy. After being off the market for 4 years, penicilloyl-polylysine was reintroduced in 2009 as PRE-PEN. We describe the negative predictive value (NPV) of PST and the impact on antibiotic selection in a sample of hospitalized patients with a reported history of penicillin allergy. METHODS We introduced a quality improvement process at our 861-bed tertiary care hospital that used PST to guide antibiotic usage in patients with a history consistent with an immunoglobulin E (IgE)-mediated reaction to penicillin. Subjects with a negative PST were then transitioned to a β-lactam agent for the remainder of their therapy. NPV of skin testing was established at 24-hour follow-up. We are reporting the result of 146 patients tested between March 2012 and July 2012. RESULTS A total of 146 patients with a history of penicillin allergy and negative PST were treated with β-lactam antibiotics. Of these, only 1 subject experienced an allergic reaction to the PST. The remaining 145 patients tolerated a full course of β-lactam therapy without an allergic response, giving the PST a 100% NPV. We estimated that PST-guided antibiotic alteration for these patients resulted in an estimated annual savings of $82,000. CONCLUSION Patients with a history of penicillin allergy who have a negative PST result are at a low risk of developing an immediate-type hypersensitivity reaction to β-lactam antibiotics. The increased use of PST may help improve antibiotic stewardship in the hospital setting. Journal of Hospital Medicine 2013;8:341–345. © 2013 Society of Hospital Medicine

Antimicrobial Susceptibility of Propionibacterium acnes Isolates from Shoulder Surgery

Abstract: Orthopedic surgeons at our institution have noticed an increase in the number of infections due to Propionibacterium acnes, especially following operations on the shoulder. We collected P. acnes isolates from our hospital microbiology laboratory for 1 year and performed antimicrobial susceptibility testing on 28 strains from the shoulder. Antibiotics with the lowest MIC values against P. acnes (MIC50 and MIC90) included penicillin G (0.006, 0.125), cephalothin (0.047 and 0.094), and ceftriaxone (0.016, 0.045), while others also showed activity. Strains resistant to clindamycin were noted.

Diagnosis of penicillin allergy revisited: the value of case history, skin testing, specific IgE and prolonged challenge.

Abstract: Background Skin testing in duplicate, correlation between case history of immediate and nonimmediate reactions and challenge outcome and prolonged oral treatment with penicillin in the diagnostic evaluation of allergic reactions to β-lactam antibiotics, mimicking real-life situations, have only been addressed in few studies. Methods A total of 342 patients suspected of having β-lactam allergy were investigated according to the European Network for Drug Allergy (ENDA) guidelines and patients found to be negative in the ENDA program were supplemented with a 7-day oral treatment with penicillin. Skin testing with penicillins was performed in duplicate. Patients with case histories of reactions to other β-lactams were also subsequently challenged with the culprit drug. Results Nineteen patients were IgE-sensitized to penicillin. Then, intracutaneous tests (ICTs) were performed, in which 35 patients tested positive for allergy, 21 with delayed and 14 with immediate reactions. Only three patients tested positive for the major (PPL) and/or minor (MDM) penicillin determinants, all being positive for penicillin G in ICT. The remaining 291 patients were challenged with penicillin: 10 tested positive in single-dose challenge and 23 tested positive in the 7-day challenge. A total of 17 of 78 patients with a negative penicillin challenge tested positive during challenges with other β-lactams. We found no correlation between case histories of immediate and nonimmediate reactions and reaction time during challenge. Conclusion The data suggest that case history is often insufficient to discriminate between immediate reactors and nonimmediate reactors. A 7-day challenge with the culprit β-lactam may yield more positive reactions than the accepted one- or 2-day challenge. Interpretation of skin testing should be made with caution.

The Empirical Combination of Vancomycin and a β-Lactam for Staphylococcal Bacteremia

Abstract: The high prevalence of methicillin resistance among Staphylococcus aureus bacteremias leads to common use of vancomycin as empirical therapy. However, investigators have reported poor outcomes with vancomycin treatment for methicillin-susceptible Staphylococcus aureus bacteremia. We review the evidence supporting empirical combination of both vancomycin and a β-lactam agent for Staphylococcus aureus bacteremia. Vancomycin therapy for methicillin-susceptible Staphylococcus aureus bacteremia is associated with 2-3 times the risk of morbidity and mortality compared to an antistaphylococcal penicillin (oxacillin and nafcillin) or first-generation cephalosporin (cefazolin). De-escalation of empirical vancomycin to definitive β-lactam therapy still appears inferior to initial β-lactam therapy. Although there is no clinical trial supporting combination therapy, a scientific rationale for benefit exists and should be weighed against the risks (adverse events, antibiotic resistance, and cost) of additional pharmacotherapy. The empirical combination of vancomycin and a β-lactam (either nafcillin, oxacillin, or cefazolin) for staphylococcal bacteremia may improve infection-related clinical outcomes.

Penicillin skin testing: potential implications for antimicrobial stewardship.

Abstract: As the progression of multidrug-resistant organisms and lack of novel antibiotics move us closer toward a potential postantibiotic era, it is paramount to preserve the longevity of current therapeutic agents. Moreover, novel interventions for antimicrobial stewardship programs are integral to combating antimicrobial resistance worldwide. One unique method that may decrease the use of second-line antibiotics (e.g., fluoroquinolones, vancomycin) while facilitating access to a preferred β-lactam regimen in numerous health care settings is a penicillin skin test. Provided that up to 10% of patients have a reported penicillin allergy, of whom ~10% have true IgE-mediated hypersensitivity, significant potential exists to utilize a penicillin skin test to safely identify those who may receive penicillin or a β-lactam antibiotic. In this article, we provide information on the background, associated costs, currently available literature, pharmacists' role, antimicrobial stewardship implications, potential barriers, and misconceptions, as well as future directions associated with the penicillin skin test.

Trends in antimicrobial resistance in Neisseria gonorrhoeae in the USA: the Gonococcal Isolate Surveillance Project (GISP), January 2006–June 2012

Abstract: Background Neisseria gonorrhoeae has progressively developed resistance to sulfonamides, penicillin, tetracycline and fluoroquinolones, and gonococcal susceptibility to cephalosporins has been declining worldwide. Methods We described trends in gonococcal antimicrobial susceptibility in the USA from January 2006 through June 2012. Susceptibility data for cefixime, ceftriaxone, azithromycin, penicillin, tetracycline and ciprofloxacin were obtained from the Gonococcal Isolate Surveillance Project (GISP), a sentinel surveillance system that monitors antimicrobial susceptibility in urethral gonococcal isolates collected from symptomatic men at 25–30 sexually transmitted disease clinics throughout the USA. Results The percentage of isolates with elevated cefixime minimum inhibitory concentrations (MICs) (≥0.25 µg/mL) increased from 0.1% in 2006 to 1.4% in 2010–2011 and was 1.1% in the first 6 months of 2012. The percentage with elevated ceftriaxone MICs (≥0.125 µg/mL) increased from 0.1% in 2006 to 0.3%–0.4% during 2009 through the first 6 months of 2012. There were no temporal trends in the prevalence of elevated azithromycin MICs (≥2 µg/mL) (0.2%–0.5%). The prevalence of resistance remained high for penicillin (11.2%–13.2%), tetracycline (16.7%–22.8%) and ciprofloxacin (9.6%–14.8%). Conclusions The proportion of gonococcal isolates with elevated cephalosporin MICs increased from 2006 to 2010, but plateaued during 2011 and the first 6 months of 2012. Resistance to previously recommended antimicrobials has persisted. As the number of antimicrobials available for gonorrhoea treatment dwindles, surveillance systems such as GISP will be critical to detect emerging resistance trends and guide treatment decisions.

Treatment of cervicofacial actinomycosis: a report of 19 cases and review of literature.

Abstract: Objectives: Actinomycosis is a chronic suppurative granulomatous infection caused by the Actinomyces genus. Orocervicofacial actinomycosis is the most common form of the disease, seen in up to 55% of cases. All forms of actinomycosis are treated with high doses of intravenous penicillin G over two to six weeks, followed by oral penicillin V. Large studies on cervicofacial actinomycosis are lacking. Therefore proper guidelines for treatment and treatment duration are difficult to establish. The aim of this study is to establish effective treatment and treat ment duration for orocervicofacial actinomycosis. Study design: A Pubmed and Embase search was performed with the focus on treatment and treatment duration for cervicofacial actinomycosis. The hospital records of all patients presenting to our department with head and neck infection from January 2000 to December 2010 were reviewed, retrospectively. The following data were collected: age, gender, clinical presentation, aetiology, duration of symptoms, microbiological findings, treatment, and duration of treatment. The treatment and treatment duration is subsequently compared to the literature. Results: The literature search provided 12 studies meeting the inclusion criteria. All studies were retrospective in nature. Penicillin or amoxicillin/clavulanic acid are the preferred antibiotic regimens found in the literature. Most of our patients were treated with a combination of penicillin G 12 million units/day and metronidazol 500 mg 3/ day, most commonly for a duration of 1 – 4 weeks, being shorter than the 3 – 52 weeks reported in the literature. Conclusion: When actinomycosis is suspected, our review has shown that a surgical approach in combination with intravenous penicillin and metronidazol until clinical improvement is seen, followed by oral antibiotics for 2 – 4 weeks is generally efficient.

Monitoring antimicrobial resistance in Neisseria gonorrhoeae in selected countries of the WHO South-East Asia Region between 2009 and 2012: a retrospective analysis

Abstract: Objective The aim of the present study was to retrospectively analyse the data reported on antimicrobial resistance (AMR) in Neisseria gonorrhoeae in six South-East Asia Region countries from 2009 to 2012 following the revitalisation of the WHO global Gonococcal Antimicrobial Surveillance Program (GASP). Methods AMR data were generated for 7 antibiotics of 4675 isolates in 18 focal point laboratories using the calibrated dichotomous sensitivity (CDS) or Clinical and Laboratory Standards Institute (CLSI) methods and minimal inhibitory concentration testing by Etest in some of the centres. The results were interpreted using the breakpoints recommended. Results High-level resistance to traditional antibiotics, penicillin (25% to 100%) and tetracycline (10% to 100%) and the previously recommended ciprofloxacin (38% to 100%) was observed in all the countries. Overall, >90% of less susceptible and resistant isolates to penicillin and ciprofloxacin were identified from 15 laboratories. Decreased susceptibility to ceftriaxone and cefpodoxime was reported by nine and eight centres, respectively. Resistance to spectinomycin (0.6% to 10.5%) and azithromycin ( Conclusions Expansion of the WHO GASP facilitated enhanced AMR surveillance to meet the ongoing challenges of control of gonococcal AMR. The results highlight that the emergence of decreased susceptibility to ceftriaxone and resistance to spectinomycin and azithromycin will unavoidably lead to loss of therapeutic options, and a search for new effective agents needs to be initiated to respond to the emergence of resistant isolates.

High frequency of fluoroquinolone- and macrolide-resistant streptococci among clinically isolated group B streptococci with reduced penicillin susceptibility

Abstract: Results: The frequency of non-susceptibility to FQs among PSGBS was 18.4% (7/38), whereas that among PRGBS was 100% (19/19). The frequency of resistance to erythromycin among PSGBS was 7.9% (3/38), while that among PRGBS was 47.4% (9/19). Statistical significance was determined using Fisher’s exact test between reduced penicillin susceptibility and FQ non-susceptibility (P ≤0.0001) and macrolide resistance (P ¼0.0012). The resistance/non-susceptibility mechanisms among PRGBS were diverse, suggesting that the PRGBS examined were not clonal. Conclusions: PRGBS isolates tend to show resistance to FQs and/or macrolides. Because the drug choice for treating these multidrug-resistant GBS is more limited than that for usual GBS, these strains may present future public health challenges.

Sensitization of Staphylococcus aureus to Methicillin and Other Antibiotics In Vitro and In Vivo in the Presence of HAMLET

Abstract: HAMLET (human alpha-lactalbumin made lethal to tumor cells) is a protein-lipid complex from human milk with both tumoricidal and bactericidal activities. HAMLET exerts a rather specific bactericidal activity against some respiratory pathogens, with highest activity against Streptococcus pneumoniae, but lacks activity against most other bacterial pathogens, including Staphylococci. Still, ion transport associated with death in S. pneumoniae is also detected to a lower degree in insensitive organisms. In this study we demonstrate that HAMLET acts as an antimicrobial adjuvant that can increase the activity of a broad spectrum of antibiotics (methicillin, vancomycin, gentamicin and erythromycin) against multi-drug resistant Staphylococcus aureus, to a degree where they become sensitive to those same antibiotics, both in antimicrobial assays against planktonic and biofilm bacteria and in an in vivo model of nasopharyngeal colonization. We show that HAMLET exerts these effects specifically by dissipating the proton gradient and inducing a sodium-dependent calcium influx that partially depolarizes the plasma membrane, the same mechanism induced during pneumococcal death. These effects results in an increased cell associated binding and/or uptake of penicillin, gentamicin and vancomycin, especially in resistant stains. Finally, HAMLET inhibits the increased resistance of methicillin seen under antibiotic pressure and the bacteria do not become resistant to the adjuvant, which is a major advantageous feature of the molecule. These results highlight HAMLET as a novel antimicrobial adjuvant with the potential to increase the clinical usefulness of antibiotics against drug resistant strains of S. aureus.

Effectiveness of penicillin, dicloxacillin and cefuroxime for penicillin-susceptible Staphylococcus aureus bacteraemia: a retrospective, propensity-score-adjusted case–control and cohort analysis

Abstract: Results: Definitive therapy with cefuroxime was associated with an increased risk of 30 day mortality compared with penicillin (adjusted HR 2.54, 95% CI 1.49‐4.32). Other variables that were statistically significantly associated with 30 day mortality included increasing age, disease severity and a primary respiratory focus. Osteomyelitis/arthritis was associated with a lower risk of death than were other secondary manifestations. Propensity-score-matched case‐control studies confirmed an increased risk of 30 day mortality: cefuroxime treatment (39%) versus penicillin treatment (20%), P ¼0.037; and cefuroxime treatment (38%) versus dicloxacillin treatment (10%), P ¼0.004. Conclusions: Definitive therapy for penicillin-susceptible SAB with cefuroxime was associated with a significantly higher mortality than was seen with therapy with penicillin or dicloxacillin.

Risk of redocumenting penicillin allergy in a cohort of patients with negative penicillin skin tests.

Abstract: BACKGROUND Even though electronic documentation of allergies is critical to patient safety, inaccuracies in documentation can potentiate serious problems. Prior studies have not evaluated factors associated with redocumenting penicillin allergy in the medical record despite a proven tolerance with a penicillin skin test (PST). OBJECTIVE Assess the prevalence of reinstating inaccurate allergy information and associated factors thereof. DESIGN We conducted a retrospective observational study from August 1, 2012 to July 31, 2013 of patients who previously had a negative PST. We reviewed records from the hospital, long-term care facilities (LTCF), and primary doctors' offices. SETTING Vidant Health, a system of 10 hospitals in North Carolina. SUBJECTS Patients with proven penicillin tolerance rehospitalized within a year period from the PST. MEASUREMENTS We gauged hospital reappearances, penicillin allergy redocumentation, residence, antimicrobial use, and presence of dementia or altered mentation. RESULTS Of the 150 patients with negative PST, 55 (37%) revisited a Vidant system hospital within a 1-year period, of whom 21 were LTCF residents. Twenty (36%) of the 55 patients had penicillin allergy redocumented without apparent reason. Factors associated with penicillin allergy redocumentation included age >65 years (P = 0.011), LTCF residence (P = 0.0001), acutely altered mentation (P < 0.0001), and dementia (P < 0.0001). Penicillin allergy was still listed in all 21 (100%) of the LTCF records. CONCLUSIONS At our hospital system, penicillin allergies are often redocumented into the medical record despite proven tolerance. The benefits of PST may be limited by inadequately removing the allergy from different electronic/paper hospital, LTCF, primary physician, and community pharmacy records. Journal of Hospital Medicine 2013;8:615–618. © 2013 Society of Hospital Medicine

Nasopharyngeal carriage, serotype distribution and antimicrobial resistance of Streptococcus pneumoniae among children from Brazil before the introduction of the 10-valent conjugate vaccine

Abstract: Streptococcus pneumoniae remains a major cause of childhood morbidity and mortality worldwide. Nasopharyngeal colonization plays an important role in the development and transmission of pneumococcal diseases, and infants and young children are considered to be the main reservoir of this pathogen. The aim of this study was to evaluate the rates and characteristics associated with nasopharyngeal carriage, the distribution of serotypes and the antimicrobial resistance profiles of Streptococcus pneumoniae among children in a large metropolitan area in Brazil before the introduction of the 10-valent pneumococcal conjugate vaccine. Between March and June 2010, nasopharyngeal swabs were collected from 242 children aged <6 years attending one day care center and the emergency room of a pediatric hospital. Pneumococcal isolates were identified by conventional methods and serotypes were determined by a sequential multiplex PCR assay and/or the Quellung reaction. The antimicrobial susceptibilities of the pneumococci were assessed by the disk diffusion method. MICs for erythromycin and penicillin were also performed. Erythromycin resistance genes were investigated by PCR. The overall colonization rate was 49.2% and it was considerably higher among children in the day care center. Pneumococcal carriage was more common among day care attenders and cohabitants with young siblings. The most prevalent serotypes were 6B, 19F, 6A, 14, 15C and 23F, which accounted for 61.2% of the isolates. All isolates were susceptible to clindamycin, levofloxacin, rifampicin and vancomycin. The highest rate of non-susceptibility was observed for sulphamethoxazole-trimethoprim (51.2%). Penicillin non-susceptible pneumococci (PNSP) accounted for 27.3% of the isolates (MICs of 0.12-4 μg/ml). Penicillin non-susceptibility was strongly associated with serotypes 14 and 23F. Hospital attendance and the presence of respiratory or general symptoms were frequently associated with PNSP carriage. The two erythromycin-resistant isolates (MICs of 2 and 4 μg/ml) belonged to serotype 6A, presented the M phenotype and harbored the mef(A/E) gene. Correlations between serotypes, settings and penicillin non-susceptibility were observed. Serotypes coverage projected for the 10-valent pneumococcal conjugate vaccine was low (45.5%), but pointed out the potential reduction of PNSP nasopharyngeal colonization by nearly 20%.

False-positive penicillin immunoassay: an unnoticed common problem.

Abstract: range of IL-31 levels between 23.1 and 111.3 pg/mL, levels in patients with mastocytosis ranged between 24.5 and 781.0 pg/mL (Fig 1, A). Interestingly, within the group of 38 adult patients, thosewith advanced disease categories, such as smoldering systemic mastocytosis and aggressive systemic mastocytosis with associated clonal hematologic non-MC lineage disease, exhibited significantly increased IL-31 levels compared with those with nonadvanced disease categories, including CM or ISM and ISM with associated clonal hematologic non-MC lineage disease (P5 .0006 [Fig 1, A] and P5 .0005 [Fig 1, B]). All IL-31 values of greater than 313.9 pg/mL were measured in patients with advanced disease categories, and none of the patients with advanced disease categories were found to exhibit IL-31 values of less than 81.9 pg/mL (Fig 1, A). As anticipated, tryptase levels increased along with disease severity (see Fig E1, A, in this article’s Online Repository at www.jacionline.org), and consistently, IL-31 was found to also correlate with tryptase in the subgroup of adult patients (P5 .0093; Fig 1, C). Furthermore, IL-31 levels correlated with the percentage of MC infiltrates in bone marrow (P5 .0404; see Fig E2, E, in this article’s Online Repository at www. jacionline.org), and patients with MC infiltrates of greater than 15% showed significantly increased IL-31 levels compared with patients with infiltrates of 15% or less (P 5 .0306; see Fig E2, F). Surprisingly, when we compared the group of 12 pediatric patients, who all had CM, with the group of 28 adult patients with CM or ISM, we observed significantly increased IL-31 levels in pediatric patients (P5 .0279; Fig 1,A). Because pediatric patients typically show lower tryptase levels than adult patients, which was also confirmed in our study (see Fig E1, A), this finding was unexpected. Analyzing different clinical parameters, we detected significantly increased IL-31 levels in male compared with female patients, which might be due to increased body weight associated with increased MC numbers in male patients (P5 .0338; see Fig E2, A). There was also a trend toward increased IL-31 expression in patients with osteosclerosis compared with that seen in patients with normal bone density, osteopenia, or osteoporosis, reflecting again the association between advanced categories of mastocytosis and high IL-31 levels because all 3 patients with osteosclerosis had either smoldering systemic mastocytosis (n 5 1) or ASMAHMND (n 5 2; not significant; see Fig E2, H). A relationship between increased bone density and increased tryptase levels has already been described. In contrast, other clinical parameters, including age, disease duration, presence of a KitD816Vmutation or skin lesions, presence of MC activation symptoms (eg, pruritus, anaphylaxis, flushing, and diarrhea), and intake of H1 antihistamines, did not affect IL-31 levels (see Fig E2,B,G, and I-P). To determine the cellular source of IL-31, we next analyzed skin and bone marrow biopsy specimens of patients with mastocytosis by using immunohistochemistry with specific antibodies against tryptase and IL-31 (Fig 2). In both tissues expression of IL-31 clearly colocalized with tryptase-positive MCs, demonstrating that MCs represent a major source of IL-31 in mastocytosis. In conclusion, our results show, for the first time, that patients withmastocytosis express increased serum IL-31 levels. In adults, IL-31 levels correlate with disease severity, tryptase levels, and percentages of bone marrow infiltration. MCs in skin and bone marrow of patients with mastocytosis are able to produce IL-31. Our data suggest exploiting IL-31 levels as a potential diagnostic marker in adult patients, particularly in patients with mastocytosis-associated osteosclerosis, which might indicate disease progression. Furthermore, to our knowledge, this is the first report on expression of IL-31 in bone marrow.

Antibiotic Treatment of Resistant Infections in Small Animals

Abstract: There are few veterinary clinical studies to support a recommended use and dose for treating resistant bacterial infections in small animals. Resistance against many common antibiotics is possible and a susceptibility test is advised. Infections caused by Pseudomonas aeruginosa presents a special problem. Staphylococcus isolated from small animals is most likely to be Staphylococcus pseudintermedius. The most important resistance mechanism for Staphylococcus is methicillin resistance. The only antimicrobials to which some gram-negative bacilli are sensitive may be extended-spectrum cephalosporins, carbapenems (penems), selected penicillin derivatives, amikacin, or tobramycin. A susceptibility test is needed to identify the appropriate drug for these infections.

Safety of benzathine penicillin for preventing congenital syphilis: a systematic review.

Abstract: Objective To estimate the risk of serious adverse reactions to benzathine penicillin in pregnant women for preventing congenital syphilis. Methods We searched for clinical trials or cohorts that assessed the incidence of serious adverse reactions to benzathine penicillin in pregnant women and the general population (indirect evidence). MEDLINE, EMBASE, Scopus and other databases were searched up to December 2012. The GRADE approach was used to assess quality of evidence. Absolute risks of each study were calculated along with their 95% confidence intervals (95% CI). We employed the DerSimonian and Laird random effects model in the meta-analyses. Results From 2,765 retrieved studies we included 13, representing 3,466,780 patients. The studies that included pregnant women were conducted to demonstrate the effectiveness of benzathine penicillin: no serious adverse reactions were reported among the 1,244 pregnant women included. In the general population, among 2,028,982 patients treated, 4 died from an adverse reaction. The pooled risk of death was virtually zero. Fifty-four cases of anaphylaxis were reported (pooled absolute risk = 0.002%; 95% CI: 0%–0.003% I2 = 12%). From that estimate, penicillin treatment would be expected to result in an incidence of 0 to 3 cases of anaphylaxis per 100,000 treated. Any adverse reactions were reported in 6,377 patients among 3,465,322 treated with penicillin (pooled absolute risk = 0.169%; 95% CI: 0.073%–0.265% I2 = 97%). The quality of evidence was very low. Conclusion Studies that assessed the risk of serious adverse events due to benzathine penicillin treatment in pregnant women were scarce, but no reports of adverse reactions were found. The incidence of severe adverse outcomes was very low in the general population. The risk of treating pregnant women with benzathine penicillin to prevent congenital syphilis appears very low and does not outweigh its benefits. Further research is needed to improve the quality of evidence.

Antibiotic resistance patterns among group B Streptococcus isolates: implications for antibiotic prophylaxis for early-onset neonatal sepsis

Abstract: Summary STUDY/PRINCIPLES: Antibiotic prophylaxis of Group B Streptococcus (GBS) positive women during labour reduces the risk of early-onset neonatal sepsis. Penicillin is the first choice, and clindamycin and erythromycin are second choices for penicillin-allergic women. Resistance to these antibiotics is rising. The aims of this study were to evaluate the rates of clindamycin and erythromycin resistance among GBS-positive isolates cultures from pregnant women in the University Hospital of Geneva and to evaluate the legitimacy of new Centres for Disease Control and Prevention (CDC) recommendations for our context. METHODS: We collected a vagino-rectal swab from pregnant women at 35‐37 weeks gestation. We recovered 124 GBS positive isolates. Identification was based on the characteristic of the colony on the chromogenic agar, the streptococcal agglutination test and confirmation by mass spectrometry. Antimicrobial susceptibility was determined by disk diffusion, according to CLSI guidelines 2010. RESULTS: The rate of resistance to clindamycin was 28% and to erythromycin was 30%. Only 3 of the 38 erythromycin resistant strains (7.9%) were susceptible to clindamycin, and only 3 out of the 35 clindamycin resistant GBS (8.6%) were identified as “inducible resistance”. The rate of co-resistance to clindamycin of erythromycin-resistant strains was 92%. Penicillin remained efficacious in all cases. CONCLUSION: Rates of clindamycin and erythromycin resistance are also increasing in our context. These antibiotics should not be used for GBS neonatal sepsis prevention, without adequate antimicrobial susceptibility testing. In case of penicillin allergy and lack of antibiogramm, cephalosporins or vancomycin should be used as recommended in CDC guidelines.

Antibiotic susceptibility of streptococcus pyogenes isolated from respiratory tract infections in dakar, senegal.

Abstract: Group A Streptococcus (GAS) is one of the major causes of respiratory tract infections. The objectives of this study were to identify isolates of S. pyogenes obtained from respiratory tract infections, and to assess their susceptibility to several antibiotics. A total of 40 strains were isolated and their susceptibility to 17 antibiotics was tested using a standard disk diffusion method. The minimum inhibitory concentrations (MICs) were determined using the E-test. All isolates were sensitive to β-lactam antibiotics including penicillin, amoxicillin, and cephalosporins. Macrolides remain active with the exception of spiramycin, which showed reduced susceptibility. Out of the 40 isolates, 100% of the isolates were resistant to tetracycline. Interestingly, isolates were sensitive to chloramphenicol, teicoplanin, vancomycine, and levofloxacin, providing potential alternative choices of treatment against infections with S. pyogenes.

Diagnosis and management of immediate hypersensitivity reactions to cephalosporins.

Abstract: Cephalosporins are one of the most commonly prescribed classes of antibiotics. Immediate IgE-mediated hypersensitivity reactions have been reported with use of a specific cephalosporin, as a cross-reaction between different cephalosporins or as a cross-reaction to other β-lactam antibiotics, namely, penicillin. Historically, frequent reports of anaphylaxis following administration of first- and second-generation cephalosporins to patients with a history of penicillin allergy led to the belief of a high degree of allergic cross-reactivity. More recent evidence reveals a significantly lower risk of cross-reactivity between penicillins and the newer-generation cephalosporins. The current thought is that a shared side chain, rather than the β-lactam ring structure, is the determining factor in immunologic cross-reactivity. Understanding the chemical structure of these agents has allowed us to identify the allergenic determinants for penicillin; however, the exact allergenic determinants of cephalosporins are less well understood. For this reason, standardized diagnostic skin testing is not available for cephalosporins as it is for penicillin. Nevertheless, skin testing to the cephalosporin in question, using a nonirritating concentration, provides additional information, which can further guide the work-up of a patient suspected of having an allergy to that drug. Together, the history and the skin test results can assist the allergist in the decision to recommend continued drug avoidance or to perform a graded challenge versus an induction of tolerance procedure.

Antibiotics for the treatment of leptospirosis: systematic review and meta-analysis of controlled trials.

Abstract: Background: Leptospirosis is a zoonotic disease prevalent mainly in developing countries and is associated with high case fatality. Antibiotics especially penicillin are the mainstay of treatment for a suspected or confirm case of leptospirosis but role of Penicillin has not been evaluated systematically in the light of current evidence. The present systematic review and meta‑analysis is done to evaluate the role of antibiotics in the treatment of leptospirosis. Methods: Parallel group clinical trials involving use of penicillin in treatment of leptospirosis were searched from all available sources. Ten clinical trials were found suitable as per laid inclusion criteria eligible for present systematic review and five clinical trials were included in meta‑analysis. Clinical trials included for meta‑analysis were compared on the basis of mortality, fever days, numbers of patients presenting with oliguria, and number of patients undergoing need‑based dialysis. Analysis was done by comprehensive meta‑analysis software 2. Qualitative outcomes are summarized as odds ratio and quantitative outcomes are summarized as standard mean difference with 95% confidence interval. Random and fixed models are used for analysis. Results: There was no significant difference between penicillin group and controlled group for mortality (Odds ratio 1.59 (95% CI 0.59-4.29), P = 0.35), fever days (std difference in mean = −0.223 (95% CI 0.394-0.995), P = 0.358), number of patients presenting with oliguria (Odds ratio 1.795 (95% CI 0.325-9.929), P = 0.502), and number of patients who underwent need based dialysis (Odds ratio 1.587 (95% CI 0.919-2.731), P = 0.098). Conclusions: Role of various antibiotics in treatment of leptospirosis is uncertain, and can be attributed to nonavailability of adequate clinical trials. Role of penicillin in the treatment of leptospirosis can be debated. Keywords: Antibiotics, doxycycline, leptospirosis, penicillin, weils disease

Lysozyme and Penicillin Inhibit the Growth of Anaerobic Ammonium-Oxidizing Planctomycetes

Abstract: Anaerobic ammonium-oxidizing (anammox) planctomycetes oxidize ammonium in the absence of molecular oxygen with nitrite as the electron acceptor. Although planctomycetes are generally assumed to lack peptidoglycan in their cell walls, recent genome data imply that the anammox bacteria have the genes necessary to synthesize peptidoglycan-like cell wall structures. In this study, we investigated the effects of two antibacterial agents that target the integrity and synthesis of peptidoglycan (lysozyme and penicillin G) on the anammox bacterium Kuenenia stuttgartiensis. The effects of these compounds were determined in both short-term batch incubations and long-term (continuous-cultivation) growth experiments in membrane bioreactors. Lysozyme at 1 g/liter (20 mM EDTA) lysed anammox cells in less than 60 min, whereas penicillin G did not have any observable short-term effects on anammox activity. Penicillin G (0.5, 1, and 5 g/liter) reversibly inhibited the growth of anammox bacteria in continuous-culture experiments. Furthermore, transcriptome analyses of the penicillin G-treated reactor and the control reactor revealed that penicillin G treatment resulted in a 10-fold decrease in the ribosome levels of the cells. One of the cell division proteins (Kustd1438) was downregulated 25-fold. Our results suggested that anammox bacteria contain peptidoglycan-like components in their cell wall that can be targeted by lysozyme and penicillin G-sensitive proteins were involved in their synthesis. Finally, we showed that a continuous membrane reactor system with free-living planktonic cells was a very powerful tool to study the physiology of slow-growing microorganisms under physiological conditions.