Showing papers on "Penicillin published in 2019"

Evaluation and Management of Penicillin Allergy: A Review.

Abstract: Importance β-Lactam antibiotics are among the safest and most effective antibiotics. Many patients report allergies to these drugs that limit their use, resulting in the use of broad-spectrum antibiotics that increase the risk for antimicrobial resistance and adverse events. Observations Approximately 10% of the US population has reported allergies to the β-lactam agent penicillin, with higher rates reported by older and hospitalized patients. Although many patients report that they are allergic to penicillin, clinically significant IgE-mediated or T lymphocyte–mediated penicillin hypersensitivity is uncommon ( 10 years) unknown reactions without features suggestive of an IgE-mediated reaction. A moderate-risk history includes urticaria or other pruritic rashes and reactions with features of IgE-mediated reactions. A high-risk history includes patients who have had anaphylaxis, positive penicillin skin testing, recurrent penicillin reactions, or hypersensitivities to multiple β-lactam antibiotics. The goals of antimicrobial stewardship are undermined when reported allergy to penicillin leads to the use of broad-spectrum antibiotics that increase the risk for antimicrobial resistance, including increased risk of methicillin-resistantStaphylococcus aureusand vancomycin-resistantEnterococcus. Broad-spectrum antimicrobial agents also increase the risk of developingClostridium difficile (also known asClostridioides difficile) infection. Direct amoxicillin challenge is appropriate for patients with low-risk allergy histories. Moderate-risk patients can be evaluated with penicillin skin testing, which carries a negative predictive value that exceeds 95% and approaches 100% when combined with amoxicillin challenge. Clinicians performing penicillin allergy evaluation need to identify what methods are supported by their available resources. Conclusions and Relevance Many patients report they are allergic to penicillin but few have clinically significant reactions. Evaluation of penicillin allergy before deciding not to use penicillin or other β-lactam antibiotics is an important tool for antimicrobial stewardship.

Group B Streptococcus (Streptococcus agalactiae)

Abstract: Invasive disease due to group B Streptococcus infection (Streptococcus agalactiae) results in a wide spectrum of clinical disease. In North America, serotypes Ia, Ib, II, III, and V are most frequently associated with invasive disease. Group B Streptococcus remains a continuing source of morbidity and mortality in high-risk populations, including pregnant women, neonates, and the elderly; an increasing incidence of invasive disease has been observed in nonpregnant adults. Group B Streptococcus remains the most common culture-confirmed neonatal bacterial infection in the United States and is a significant source of neonatal morbidity globally. Intrapartum antibiotic prophylaxis has reduced the incidence of early-onset neonatal disease without a notable impact on the incidence of late-onset neonatal disease. Penicillin G remains the mainstay of therapy, although reduced penicillin susceptibility has been observed in select isolates. Increased frequency of resistance to non-beta-lactam antibiotics, including clindamycin, erythromycin, and fluoroquinolones, has been observed, with some isolates demonstrating resistance to vancomycin. The development and implementation of strategies to identify hosts, treat judiciously with antimicrobials with the narrowest spectra, and prevent invasive disease, with vaccines, are essential to reduce the burden of group B Streptococcus disease.

Impact of intrapartum and postnatal antibiotics on the gut microbiome and emergence of antimicrobial resistance in infants.

Abstract: Altogether, 20–30% of women receive intrapartum antibiotic prophylaxis (IAP) to prevent sepsis in infants and 2–5% of newborn infants receive antibiotics due to suspected sepsis. Caesarean section has a long-term impact on the intestinal microbiome but the effects of perinatal antibiotics on gut microbiome in vaginally delivered infants are not well known. We compared the impact of IAP, postnatal antibiotics, or their combination on the gut microbiome and emergence of antimicrobial resistance in a controlled study of 149 newborn infants recruited within 24 hours after birth. We collected 659 fecal samples, including 426 daily samples from infants before discharge from the hospital and 111 follow-up samples at six months. Penicillin was mostly used for IAP and the combination of penicillin and aminoglycoside for postnatal treatment. Postnatal antibiotic groups received Lactobacillus reuteri probiotic. Newborn gut colonization differed in both IAP and postnatal antibiotics groups as compared to that in control group. The effect size of IAP was comparable to that caused by postnatal antibiotics. The observed differences were still present at six months and not prevented by lactobacilli consumption. Given the present clinical results, the impact of perinatal antibiotics on the subsequent health of newborn infants should be further evaluated.

OXA-1 β-lactamase and non-susceptibility to penicillin/β-lactamase inhibitor combinations among ESBL-producing Escherichia coli

Abstract: Background ESBL-producing Escherichia coli have expanded globally since the turn of the century and present a major public health issue. Their in vitro susceptibility to penicillin/inhibitor combinations is variable, and clinical use of these combinations against ESBL producers remains controversial. We hypothesized that this variability related to co-production of OXA-1 penicillinase. Methods During a national study we collected 293 ESBL-producing E. coli from bacteraemias, determined MICs by BSAC agar dilution, and undertook genomic sequencing with Illumina methodology. Results The collection was dominated by ST131 (n = 188 isolates, 64.2%) and blaCTX-M-15 (present in 229 isolates, 78.2%); over half the isolates (159/293, 54.3%) were ST131 with blaCTX-M-15. blaOXA-1 was found in 149 ESBL producers (50.9%) and blaTEM-1/191 in 137 (46.8%). Irrespective of whether all isolates were considered, or ST131 alone, there were strong associations (P < 0.001) between co-carriage of blaOXA-1 and reduced susceptibility to penicillin/inhibitor combinations, whereas there was no significant association with co-carriage of blaTEM-1/191. For piperacillin/tazobactam the modal MIC rose from 2 mg/L in the absence of blaOXA-1 to 8 or 16 mg/L in its presence; for co-amoxiclav the shift was smaller, from 4 or 8 to 16 mg/L, but crossed the breakpoint. blaOXA-1 was strongly associated with co-carriage also of aac(6′)-Ib-cr, which compromises amikacin and tobramycin. Conclusions Co-carriage of OXA-1, a penicillinase with weak affinity for inhibitors, is a major correlate of resistance to piperacillin/tazobactam and co-amoxiclav in E. coli and is commonly associated with co-carriage of aac(6′)-Ib-cr, which narrows aminoglycoside options.

Evaluating Penicillin Allergies Without Skin Testing.

Abstract: An unconfirmed penicillin allergy is known to confer significant risk to patients. Only a small minority of patients labeled with penicillin allergy will be confirmed to be hypersensitive with the current reference standard test, an oral amoxicillin therapeutic dose challenge. Skin testing has been recommended prior to oral challenges to reduce the risk of severe acute challenge reactions. The rate of severe acute anaphylactic reactions with oral amoxicillin is currently extremely low. Unfortunately, penicillin skin testing, as commonly performed, has a high rate of false positive results. Encouraging skin testing in all individuals with an unconfirmed penicillin allergy, prior to a confirmatory oral challenge, would be technically difficult, make testing all individuals with an unconfirmed penicillin allergy very unlikely, and ultimately increase the risk to patients because of suboptimal antibiotic use. Most patients, who are appropriate candidates for a direct oral amoxicillin challenge, to confirm current penicillin tolerance, can be safely identified by their clinical histories. Higher risk individuals, those with a history of anaphylaxis or other acute onset potentially IgE-mediated reaction such as hives within 6 h of the first dose of the last course of a penicillin, may benefit from properly performed puncture and intradermal skin testing, using commercially available penicilloyl-polylysine, prior to an oral challenge, if skin test negative. Direct oral amoxicillin challenges in low-risk individuals are well accepted by patients and a safe and effective part of penicillin allergy delabeling.

Implementation of a pharmacist-led penicillin allergy de-labelling service in a public hospital.

Abstract: Background Inaccurate allergy labelling results in inappropriate antimicrobial management of the patient, which may affect clinical outcome, increase the risk of adverse events and increase costs. Inappropriate use of alternative antibiotics has implications for antimicrobial stewardship programmes and microbial resistance. Methods All adult inpatients labelled as penicillin allergic were identified and screened for eligibility by the study pharmacist. An accurate allergy and medication history was taken. Patients were 'de-labelled', underwent oral challenge or were referred to an immunology clinic, if study criteria were met. All patients included in the study were followed-up 1 year after intervention. Results Two hundred and fifty eligible patients with a label of 'penicillin allergy' were identified. The prevalence of reported penicillin allergy at Middlemore Hospital was 11%. We found that 80% of study patients could be 'de-labelled'. Of those, 80% were 'de-labelled' after an interview with the pharmacist alone, 16% had an uneventful oral challenge and 4% were deemed to be inappropriately labelled after referral to an immunology clinic. Appropriately labelled patients accounted for 20% of the study population. Changes to inpatient antibiotic therapy were recommended in 61% of 'de-labelled' patients, of which no patients had adverse events after commencing on penicillin antibiotics. At the 1 year follow-up, 98% of patients who were 'de-labelled' had no adverse events to repeated administration of penicillin antibiotics. Conclusions This study showed that a pharmacist-led allergy management service is a safe option to promote antimicrobial stewardship and appropriate allergy labelling.

Evaluation of a pharmacist-led penicillin allergy de-labelling ward round: a novel antimicrobial stewardship intervention

Abstract: BACKGROUND: Antibiotic allergy labels (AALs), reported by up to 25% of hospitalized patients, are a significant barrier to appropriate prescribing and a focus of antimicrobial stewardship (AMS) programmes. METHODS: A prospective audit of a pharmacist-led AMS penicillin allergy de-labelling ward round at Austin Health (Melbourne, Australia) was evaluated. Eligible inpatients with a documented penicillin allergy receiving an antibiotic were identified via an electronic medical report and then reviewed by a pharmacist-led AMS team. The audit outcomes evaluated were: (i) AMS post-prescription review recommendations; (ii) direct de-labelling; (iii) inpatient oral rechallenge referral; (iv) skin prick testing/intradermal testing referral; and (v) outpatient antibiotic allergy clinic assessment. RESULTS: Across a 5 month period, 106 patients were identified from a real-time electronic prescribing antibiotic allergy report. The highest rate of penicillin allergy de-labelling was demonstrated in patients who were referred for an inpatient oral rechallenge with 95.2% (n = 21) successfully having their penicillin AAL removed. From the 22 patients with Type A reactions, 63.6% had their penicillin AAL removed. We demonstrated a significant decrease in the prescribing of restricted antibiotics (defined as third- or fourth-generation cephalosporins, fluoroquinolones, glycopeptides, carbapenems, piperacillin/tazobactam, lincosamides, linezolid or daptomycin) in patients reviewed (pre 42.5% versus post 17.9%, P = 0.0002). CONCLUSIONS: A pharmacist-led AMS penicillin allergy de-labelling ward round reduced penicillin AALs and the prescribing of restricted antibiotics. This model could be implemented at other hospitals with existing AMS programmes.

Antibiotic resistance in porcine pathogenic bacteria and relation to antibiotic usage

Abstract: Optimal treatment and prudent use of antimicrobials for pigs is imperative to secure animal health and prevent development of critical resistance. An important step in this one-health context is to monitor resistance patterns of important animal pathogens. The aim of this study was to investigate the antimicrobial resistance patterns of five major pathogens in Danish pigs during a period from 2004 to 2017 and elucidate any developments or associations between resistance and usage of antibiotics. The minimum inhibitory concentration (MIC) for Escherichia coli, Actinobacillus pleuropneumoniae, Streptococcus suis, Bordetella bronchiseptica, and Staphylococcus hyicus was determined to representatives of antibiotic classes relevant for treatment or surveillance. Escherichia coli isolates were mostly sensitive to fluoroquinolones and colistin, whereas high levels of resistance were observed to ampicillin, spectinomycin, streptomycin, sulfonamides and tetracycline. While resistance levels to most compounds remained relatively stable during the period, resistance to florfenicol increased from 2.1% in 2004 to 18.1% in 2017, likely in response to a concurrent increase in usage. A temporal association between resistance and usage was also observed for neomycin. E. coli serovars O138 and O149 were generally more resistant than O139. For A. pleuropneumoniae, the resistance pattern was homogenous and predictable throughout the study period, displaying high MIC values only to erythromycin whereas almost all isolates were susceptible to all other compounds. Most S. suis isolates were sensitive to penicillin whereas high resistance levels to erythromycin and tetracycline were recorded, and resistance to erythromycin and trimethoprim increasing over time. For S. hyicus, sensitivity to the majority of the antimicrobials tested was observed. However, penicillin resistance was recorded in 69.4–88.9% of the isolates. All B. bronchiseptica isolates were resistant to ampicillin, whereas all but two isolates were sensitive to florfenicol. The data obtained have served as background for a recent formulation of evidence-based treatment guidelines for pigs. Antibiotic resistance varied for some pathogens over time and in response to usage. Resistance to critically important compounds was low. The results emphasize the need for continuous surveillance of resistance patterns also in pig pathogenic bacteria.

Synergistic Antibacterial Activity of Designed Trp-Containing Antibacterial Peptides in Combination With Antibiotics Against Multidrug-Resistant Staphylococcus epidermidis.

Abstract: Multidrug resistance among various bacterial strains is leading to worldwide resistance to a wide range of antibiotics. Combination therapy involving current antibiotics and other biological or chemical molecules represents an attractive novel strategy. In this study, we investigated the synergistic antibacterial activity of a series of Trp-containing antimicrobial peptides (AMPs) with four classes of traditional chemical antibiotics that are inactive against multidrug-resistant Staphylococcus epidermidis (MRSE) in vitro and in vivo. Among the antibiotics that we studied, penicillin, ampicillin and erythromycin showed a distinct synergistic effect in combination with all of the Trp-containing AMPs, represented by a fractional inhibitory concentration index (FICI) of <0.5. The antibacterial activities were noticeably improved, with 32-to 64-fold reductions in the MIC values for ampicillin and 16- to 32-fold reductions in the MIC values for erythromycin and penicillin. Tetracycline showed synergistic activity with only I1WL5W but additive activity with L11W, L12W, and I4WL5W. Ceftazidime exhibited additive activity with the Trp-containing peptides. In addition, the antibiotics in combination with the peptide significantly inhibited biofilm formation by MRSE 1208. A mechanistic study demonstrated that the Trp-containing peptides, especially I1WL5W and I4WL5W, which contain two tryptophan residues, disrupted bacterial inner and outer membranes, which promoted antibiotic delivery into the cytoplasm and access to cytoplasmic targets; however, L11W and L12W may have increased intracellular antibiotic concentrations by decreasing blaZ, tet(m) and msrA expression. Importantly, strong synergistic activity against the MRSE 1208 strain was observed for the combination of I1WL5W and penicillin in a mouse infection model. Thus, the combination of AMPs and traditional antibiotics could be a promising option for the prevention of acute and chronic infections caused by MRSE.

Risk of Adverse Reactions to Oral Antibiotics Prescribed by Dentists.

Abstract: Dentists prescribe a large portion of all oral antibiotics, and these are associated with a risk of adverse drug reactions (ADRs). The aim of this study was to quantify the risk of ADRs associated with oral antibiotics commonly prescribed by dentists. NHS Digital Prescribing data and Yellow Card Drug Analysis data for 2010 to 2017 were abstracted to quantify dental antibiotic prescribing in England, and the rate and types of ADRs associated with them. During the period of study, the mean number of actively practicing dentists in England was 23,624. Amoxicillin accounted for 64.8% of dental antibiotic prescribing and had the lowest reported rate of fatal ADRs (0.1/million prescriptions) and overall ADRs (21.5/million prescriptions). Indeed, amoxicillin was respectively 6 and 3 times less likely to cause an ADR than the other penicillins, penicillin V and amoxicillin + clavulanic acid, and appears to be very safe in patients with no history of penicillin allergy. In contrast, clindamycin, which is often used in patients with penicillin allergy, had the highest rate of fatal (2.9/million prescriptions) and overall (337.3/million prescriptions) ADRs, with Clostridiodes (formerly Clostridium) difficile infections pivotal to its ADR profile. Other amoxicillin alternatives, clarithromycin and metronidazole, while significantly worse than amoxicillin, were 3 and nearly 5 times less likely to cause an ADR than clindamycin. Ranked from least to most likely to cause an ADR, antibiotics most commonly prescribed were as follows: amoxicillin < cephalosporins < erythromycin < tetracyclines < azithromycin < metronidazole < amoxicillin + clavulanic acid < clarithromycin < penicillin V < clindamycin. This study confirmed the high level of safety associated with use of amoxicillin by dentists and the significantly worse rates of fatal and nonfatal ADRs associated with other penicillins and alternatives to amoxicillin for those who are penicillin allergic. In particular, clindamycin had the highest rate of fatal and nonfatal ADRs of any of the antibiotics commonly prescribed by dentists.

Genomic identification of cryptic susceptibility to penicillins and β-lactamase inhibitors in methicillin-resistant Staphylococcus aureus.

Abstract: Antibiotic resistance in bacterial pathogens threatens the future of modern medicine. One such resistant pathogen is methicillin-resistant Staphylococcus aureus (MRSA), which is resistant to nearly all β-lactam antibiotics, limiting treatment options. Here, we show that a significant proportion of MRSA isolates from different lineages, including the epidemic USA300 lineage, are susceptible to penicillins when used in combination with β-lactamase inhibitors such as clavulanic acid. Susceptibility is mediated by a combination of two different mutations in the mecA promoter region that lowers mecA-encoded penicillin-binding protein 2a (PBP2a) expression, and in the majority of isolates by either one of two substitutions in PBP2a (E246G or M122I) that increase the affinity of PBP2a for penicillin in the presence of clavulanic acid. Treatment of S. aureus infections in wax moth and mouse models shows that penicillin/β-lactamase inhibitor susceptibility can be exploited as an effective therapeutic choice for 'susceptible' MRSA infection. Finally, we show that isolates with the PBP2a E246G substitution have a growth advantage in the presence of penicillin but the absence of clavulanic acid, which suggests that penicillin/β-lactamase susceptibility is an example of collateral sensitivity (resistance to one antibiotic increases sensitivity to another). Our findings suggest that widely available and currently disregarded antibiotics could be effective in a significant proportion of MRSA infections.

Direct oral amoxicillin challenge without preliminary skin testing in adult patients with allergy and at low risk with reported penicillin allergy.

Abstract: Introduction: Ten percent of hospitalized patients report penicillin allergy; however, recent studies indicate that ∼98% of these patients are not acutely hypersensitive. Unconfirmed penicillin allergy poses public health risks, and an evaluation of penicillin allergy labels is recommended to improve antibiotic stewardship. Although the most widely accepted protocol is penicillin skin testing, followed by oral amoxicillin challenge, time constraints and resources may preclude this. Recent literature supports the safety and efficacy of direct oral amoxicillin challenge in individuals at low risk. Methods: We retrospectively evaluated direct oral challenge acceptance and outcomes in eligible adult outpatients with allergy and with a penicillin allergy label over a 6-month period. Direct oral amoxicillin challenge was recommended in patients with a history of benign rash, benign somatic symptoms, or unknown history associated with the last penicillin exposure >12 months ago. Those with severe reactions or reactions within 12 months of evaluation were not challenged. The patients were monitored for 60 minutes after challenge and were discharged with instructions to call in the event of a delayed reaction. Results: There were 50 of 355 adults (14%) with a penicillin allergy label seen by a single allergist; of these patients, 38 (76%) met our criteria for a direct oral challenge. The index penicillin associated reactions were mostly remote, and 44 subjects (88%) reported reactions >10 years earlier. Four patients (8%) were de-labeled based on history alone. Twenty subjects (40%) consented to challenge in the clinic, and none developed immediate, or to our knowledge, delayed hypersensitivity reactions. Three of 20 patients (15%) developed self-limited subjective symptoms that were not deemed to constitute true immunoglobulin E mediated hypersensitivity. A total of 24 patients (48%) had the penicillin allergy label removed from their medical record. Conclusion: This study added to the accumulating body of evidence that supports the safety and efficacy of direct provocative challenge without preliminary skin testing to exclude penicillin allergy in individuals at low risk. Larger prospective studies are necessary to confirm these observations.

Evaluation of Antibiotics Residues in Chicken Meat Samples in Lebanon

Abstract: Antibiotic residue in chicken is a human health concern due to its harmful effects on consumer health. This study aims at screening the antibiotic residues from 80 chicken samples collected from farms located in different regions of Lebanon. An optimized multi-class method for identification and quantification of 30 antibiotics from four different chemical classes (sulfonamides, tetracyclines, quinolones, and beta-lactams) has been developed by using liquid chromatography-mass spectrometry. The evaluation of antibiotics residues in 80 chicken muscles samples has shown that 77.5% of samples were at least contaminated with antibiotics residues, out of which 53.75% were exposed to co-occurrence of multidrug residues. The screening of the four antibiotics families has shown that ciprofloxacin (quinolones) represents the highest occurrence percentage (32.5%), followed by amoxicillin (β-lactams) (22.5%) and then tetracyclines (17.5%). Means of sarafloxacin, amoxicillin, and penicillin G residues levels were above the Maximum Residue Limit (MRL) recommended limit according to the European Union EC. This study revealed that chicken samples collected from Lebanese farms contain antibiotic residues. Guidelines for prudent use of antimicrobials agents for chicken should be adopted to reduce the prevalence of resistant Salmonella in chicken.

Staphylococcus lugdunensis:antimicrobial susceptibility and optimal treatment options

Abstract: Staphylococcus lugdunensis is a coagulase-negative staphylococcus (CoNS) with unusual pathogenicity resembling that of S. aureus. Unlike other CoNS, S. lugdunensis remains susceptible to most antibiotics. The resistance to penicillin varies widely (range, 15-87% worldwide), whereas methicillin resistance is still rare. We aimed to evaluate treatment options for infections caused by S. lugdunensis and more specifically to investigate whether penicillin G could be a better treatment choice than oxacillin. Susceptibility testing was performed using the disc diffusion method for penicillin G, cefoxitin, trimethoprim/sulfamethoxazole, erythromycin, clindamycin, gentamicin, norfloxacin, fusidic acid, rifampicin, and fosfomycin. Isolates susceptible to penicillin G were further tested with a gradient test for penicillin G and oxacillin. Of the 540 clinical isolates tested, 74.6% were susceptible to penicillin G. Among these penicillin-susceptible isolates, the MIC50 and MIC90 values for penicillin G were threefold lower than that for oxacillin. A majority of the isolates were susceptible to all other antibiotics tested. Breakpoints for fosfomycin have not yet been defined, and so no conclusions could be drawn. Two isolates were resistant to cefoxitin and carried the mecA gene; whole-genome sequencing revealed that both harbored the SCCmec element type IVa(2B). S. lugdunensis isolated in Sweden were susceptible to most tested antibiotics. Penicillin G may be a more optimal treatment choice than oxacillin. Although carriage of the mecA gene is rare among S. lugdunensis, it does occur.

Virulence factors and antibiotic resistance properties of the Staphylococcus epidermidis strains isolated from hospital infections in Ahvaz, Iran.

Abstract: Resistant Staphylococcus epidermidis strains are considered to be one of the major causes of human clinical infections in hospitals. The present investigation was done to study the pattern of antibiotic resistance and the prevalence of virulence and antibiotic resistance genes amongst the S. epidermidis strains isolated from human hospital infections. One hundred hospital infectious samples were collected and S. epidermidis strains were identified using culture and biochemical tests. Isolated strains were subjected to disk diffusion and PCR. Forty-six out of 100 hospital infectious samples (46%) were positive for S. epidermidis. S. epidermidis strains harbored the highest prevalence of resistance against penicillin (95.65%), tetracycline (91.30%), erythromycin (82.60%), cefazolin (78.26%), and trimethoprim-sulfamethoxazole (73.91%). All S. epidermidis strains had resistance against at least three different types of antibiotics, while the prevalence of resistance against more than seven types of antibiotics was 17.39%. AacA-D (69.56%), tetK (56.52%), mecA (45.65%), msrA (39.13%), and tetM (39.13%) were most commonly detected antibiotic resistance genes. The prevalence of vatC (4.34%), ermA (8.69%), vatA (8.69%), vatB (13.04%), ermC (13.04%), and linA (10.86%) were lower than other detected antibiotic resistance genes. ClfA (32.60%), agrIII (17.39%), and etB (13.04%) were the most commonly detected virulence factors. The presence of virulent and multi-drug resistance S. epidermidis strains showed an important public health issue in hospitals.

Resistance of Neisseria gonorrhoeae isolates to beta-lactam antibiotics (benzylpenicillin and ceftriaxone) in Russia, 2015-2017.

Abstract: The goal of this work was to study the phenotypic susceptibility and resistance determinants of N. gonorrhoeae isolates to beta-lactam antimicrobials (benzylpenicillin and ceftriaxone). A total of 522 clinical isolates collected in Russia in 2015-2017 were analysed for susceptibility using the agar dilution method. DNA loci involved in antimicrobial resistance were identified using DNA microarray analysis and sequencing. Resistance to benzylpenicillin remained high, with 7.7% of isolates resistant (MICpen > 1 mg/L) and 47.5% of isolates showing intermediate susceptibility (MICpen = 0.12-1 mg/L). The most frequent resistance determinant (72.4% isolates) was the Asp345 insertion in penA, both as a single mutation and in combination with other mutations, particularly with the substitution Leu421Pro in ponA (39.0%). Mutations affecting the influx and efflux of drugs were also found, including amino acid substitutions in PorB (26.8% isolates) and delA in the promoter region of mtrR (22.8%). The accumulation of mutations in chromosomal genes (penA, pon, porA, and mtrR) led to a stepwise increase in MICpen to values characteristic of intermediate resistance. The presence of blaTEM plasmids was found in 25 isolates (4.8%), resulting in a strong increase in resistance to penicillin (MICpen > 16 mg/L) compared with the chromosomal mutations; 23 plasmids were of the African type with TEM-1 beta-lactamase, and two plasmids were of the Toronto/Rio type with TEM-135 beta-lactamase. Only three isolates were found with reduced susceptibility to ceftriaxone, with MICcef = 0.12-0.25 mg/L. Sequencing of penA did not reveal mutations associated with resistance to third-generation cephalosporins, and the gene structure was non-mosaic. The majority of isolates (21 of 25) carrying the blaTEM plasmid also contained the conjugative plasmid with tetM (resistance to tetracyclines), consistent with previously reported data that the presence of the conjugative plasmid facilitates the transfer of other plasmids associated with antimicrobial resistance.

Trends in antimicrobial resistance of bacterial pathogens in Harare, Zimbabwe, 2012-2017: a secondary dataset analysis

Abstract: Antimicrobial resistance is one of the most serious public health threats of the twenty-first century. The implementation of AMR surveillance in Zimbabwe is limited. However, data from a private laboratory in Harare revealed increasing resistance rates to common antibiotics like ampicillin (i.e., from 73.9% in 2011 to 74.6% in 2015). The increasing resistance rates indicate that Zimbabwe is affected by AMR. This study was done to determine the magnitude of AMR in Harare and determine the trends of AMR to first-line and to last-resort antibiotics and make recommendations to mitigate the problem. A retrospective record review of data collected from the microbiology department at a private laboratory between January 2012 and December 2017 was done. The outcome of interest was the antibiotic susceptibility of bacterial isolates. Microsoft Excel 2016 was used to plot trends from 2012 to 2017 and Epi Info™7 was used for statistical analysis. A total of 23,432 isolates, of 12 medically important bacteria were analysed. Forty-three percent of the isolates were from urines, 36.7% were from pus swabs and 7% were from blood. The most common pathogen was Escherichia coli (43.2%), followed by Staphylococcus aureus (15.8%) and the least common was Neisseria gonorrhoea (0.2%). Resistance was highest to ampicillin followed by penicillin, both ranging between 70 and 100% over the six years. Statistically significant increases in resistance to commonly used antibiotics were observed in amoxicillin-resistant E. coli and Streptococcus pneumonia and third generation cephalosporin-resistant E. coli. There was an increase in resistance to last-line antibiotics i.e., fluoroquinolone-resistant Salmonella spp. and carbapenem-resistant Pseudomonas aeruginosa and Acinetobacter baumannii. However, methicillin-resistant S. aureus showed a decreasing trend. There is a high burden of drug resistance to common antibiotics in Harare and an emergence of resistance to last-line antibiotics.

Penicillin V four times daily for five days versus three times daily for 10 days in patients with pharyngotonsillitis caused by group A streptococci: randomised controlled, open label, non-inferiority study.

Abstract: Objective To determine whether total exposure to penicillin V can be reduced while maintaining adequate clinical efficacy when treating pharyngotonsillitis caused by group A streptococci. Design Open label, randomised controlled non-inferiority study. Setting 17 primary healthcare centres in Sweden between September 2015 and February 2018. Participants Patients aged 6 years and over with pharyngotonsillitis caused by group A streptococci and three or four Centor criteria (fever ≥38.5°C, tender lymph nodes, coatings of the tonsils, and absence of cough). Interventions Penicillin V 800 mg four times daily for five days (total 16 g) compared with the current recommended dose of 1000 mg three times daily for 10 days (total 30 g). Main outcome measures Primary outcome was clinical cure five to seven days after the end of antibiotic treatment. The non-inferiority margin was prespecified to 10 percentage points. Secondary outcomes were bacteriological eradication, time to relief of symptoms, frequency of relapses, complications and new tonsillitis, and patterns of adverse events. Results Patients (n=433) were randomly allocated to the five day (n=215) or 10 day (n=218) regimen. Clinical cure in the per protocol population was 89.6% (n=181/202) in the five day group and 93.3% (n=182/195) in the 10 day group (95% confidence interval −9.7 to 2.2). Bacteriological eradication was 80.4% (n=156/194) in the five day group and 90.7% (n=165/182) in the 10 day group. Eight and seven patients had relapses, no patients and four patients had complications, and six and 13 patients had new tonsillitis in the five day and 10 day groups, respectively. Time to relief of symptoms was shorter in the five day group. Adverse events were mainly diarrhoea, nausea, and vulvovaginal disorders; the 10 day group had higher incidence and longer duration of adverse events. Conclusions Penicillin V four times daily for five days was non-inferior in clinical outcome to penicillin V three times daily for 10 days in patients with pharyngotonsillitis caused by group A streptococci. The number of relapses and complications did not differ between the two intervention groups. Five day treatment with penicillin V four times daily might be an alternative to the currently recommended 10 day regimen. Trial registration EudraCT 2015-001752-30; ClinicalTrials.govNCT02712307.

The Impact of Patient-Reported Penicillin Allergy on Risk for Surgical Site Infection in Total Joint Arthroplasty.

Abstract: Background:Penicillin (PCN) allergy is reported in 10% to 20% of the population; studies show that only 1% to 3% of patients have a true allergy. Most patients reporting a PCN allergy receive second-line antibiotic prophylaxis preoperatively, which raises concerns about antimicrobial efficacy. Studi