Penicillin-resistant Organisms Research Articles

Utilization of a kinetic isotope effect to decrease decomposition of ceftriaxone in a mixture of D2O/H2O

The discovery of cephalosporin and demonstration of its improved stability in aqueous solution, as well as enhanced in vitro activity against penicillin-resistant organisms, were major breakthroughs in the development of β-lactam antibiotics. Although cephalosporins are more stable with respect to hydrolytic degradation than penicillins, they still experience a variety of chemical transformations. The present study offers an insight into the rates and mechanisms of ceftriaxone degradation at the therapeutic concentration in water, a mixture of water and deuterium oxide, and deuterium oxide itself at the neutral pH.Specific ceftriaxone degradation products were observed in aged samples (including a previously unreported dimer-type species), and by comparing the degradation rates in H2O and D2O, the observation of a kinetic isotope effect provided some valuable insight as to the nature of the initial ceftriaxone degradation. The effect of protium to deuterium isotope change on the degradation kinetics of ceftriaxone was evaluated using the method of initial rates based on HPLC analysis as well as by quantitative 1H NMR spectroscopy. Moreover, computational analysis was utilized to get a molecular insight into chemical processes governing the ceftriaxone degradation and to rationalize the stabilizing effect of replacing H2O with D2O.

Antibiotic resistance in severe odontogenic infections of the South Australian population: a 9-year retrospective audit.

The aims of this study were to evaluate the microbiological trends in severe odontogenic infections requiring hospital admission in the South Australian Oral and Maxillofacial Surgery Unit. Rates of antibiotic resistance to empirical antibiotic regimens were determined to quantify the clinical implications of antibiotic-resistant odontogenic infections. A retrospective case audit was performed on all odontogenic infections admitted to the Royal Adelaide Hospital over a 9-year period. Data was collected regarding demographics, microbiological culture and sensitivity results, and clinical outcome variables. Of a total of 672 patients, microbiology data was available for 447 cases. Penicillin-resistant organisms were identified in 10.8% of patients, who required a significantly longer length of hospital admission (mean, 9.93days) and higher rates of non-response to initial surgical therapy (40%). There were moderate rates of antibiotic-resistant odontogenic infections within the South Australian population. Patients within this subgroup demonstrate markedly poorer clinical outcomes. Effective treatment of odontogenic infections involves early operative intervention, with adjunctive use of appropriate antibiotic therapy that involves close monitoring of response to removal of the cause and use of first-line antibiotic agents. Cases that fail to respond require urgent specialist review in order to reduce morbidity and mortality outcomes.

Microbial causes of complicated acute bacterial rhinosinusitis and implications for empirical antimicrobial therapy.

Very little up-to-date information is available on the microbiology of complicated acute bacterial rhinosinusitis. Reliable microbiology testing is necessary to inform current empirical antimicrobial treatments. This study was conducted in response to recent US guidelines on antimicrobial treatments for acute bacterial rhinosinusitis. It aimed to describe the pathological micro-organisms involved in complicated acute bacterial rhinosinusitis in the UK and their antimicrobial susceptibility. This study collected retrospective data on cases of complicated acute bacterial rhinosinusitis with sinogenic orbital and/or intracranial infections from 2007 to 2012. Bacteria identified in paranasal sinus pus were compared with those identified in orbital and/or intracranial infections. Streptococcus anginosus group bacteria were isolated from 61.3 per cent of paranasal sinus pus samples, 83.3 per cent of orbital infections and 77.8 per cent of intracranial infections. All S anginosus isolates were sensitive to penicillin; no penicillin-resistant organisms were isolated. S anginosus was the predominant organism isolated from complicated acute bacterial rhinosinusitis samples at our UK centre. S anginosus is sensitive to penicillin, suggesting that penicillin can be used as an appropriate first-line empirical antibiotic for uncomplicated acute bacterial rhinosinusitis.

Gram Staining for the Treatment of Peritonsillar Abscess

Objective. To examine whether Gram staining can influence the choice of antibiotic for the treatment of peritonsillar abscess. Methods. Between 2005 and 2009, a total of 57 cases of peritonsillar abscess were analyzed with regard to cultured bacteria and Gram staining. Results. Only aerobes were cultured in 16% of cases, and only anaerobes were cultured in 51% of cases. Mixed growth of aerobes and anaerobes was observed in 21% of cases. The cultured bacteria were mainly aerobic Streptococcus, anaerobic Gram-positive cocci, and anaerobic Gram-negative rods. Phagocytosis of bacteria on Gram staining was observed in 9 cases. The bacteria cultured from these cases were aerobic Streptococcus, anaerobic Gram-positive cocci, and anaerobic Gram-negative rods. The sensitivity of Gram staining for the Gram-positive cocci and Gram-negative rods was 90% and 64%, respectively. The specificity of Gram staining for the Gram-positive cocci and Gram-negative rods was 62% and 76%, respectively. Most of the Gram-positive cocci were sensitive to penicillin, but some of anaerobic Gram-negative rods were resistant to penicillin. Conclusion. When Gram staining shows only Gram-positive cocci, penicillin is the treatment of choice. In other cases, antibiotics effective for the penicillin-resistant organisms should be used.

Outbreak of meningococcal disease in and around New Delhi, India, 2005–2006: a report from a tertiary care hospital

The first of several cases of meningococcal meningitis was reported in April 2005, in New Delhi, India. Subsequent to this the Government declared an outbreak, which persisted for two periods, from April-July 2005 and January-March 2006. The National Institute of Communicable Diseases (NICD) recommended using WHO criteria for diagnosis of disease. During the outbreak 380 clinically suspected cases were investigated. Of 55 cases diagnosed as confirmed/probable the mortality rate was 14.6%. Meningitis was reported in 60% of cases and meningococcaemia in 40%. Microscopy of petechial rash was positive in 87.5%, CSF Gram stain positive in 68.3%, and latex agglutination test of CSF positive in 64.9% of samples. Neisseria meningitidis (serogroup A) was isolated from 37.7% of cases, 57.7% from CSF. Blood culture was positive in 10.4% of cases. CrgA polymerase chain reaction for N. meningitidis confirmed the isolates. All isolates were susceptible to third-generation cephalosporins, azithromycin and rifampicin, with increasing resistance to ceftriaxone. Penicillin resistance was encountered in 15.4% of strains. Resistance to quinolones was very high at 100% for levofloxacin, 84.6% for ofloxacin and 65.4% for ciprofloxacin. All patients with penicillin-resistant organisms (4) or intermediate sensitivity (4) succumbed to the disease. These patients also had a higher minimum inhibitory concentration to ceftriaxone.

Arthrite sans urétrite: penser au gonocoque

Septic arthritis caused by Neisseria gonorrhoeae is mono or pauciarticular. They represent a nonrare cause of arthritis in sexually active adults. He is necessary to think of it even in the absence of urethritis. We report the case of gonococcal arthritis without urethritis in a young man associated with positive synovial fluid culture and negative blood cultures. Prompt recognition and treatment of this disease results in cure without aftereffects. The finding of penicillin-resistant organisms reinforces recent recommendations that advanced-generation cephalosporin must be used as initial therapy.

THE CLASSIC: Penicillin: Its Practical Application in Orthopaedic Surgery and Fractures

THE CLASSIC: Penicillin: Its Practical Application in Orthopaedic Surgery and Fractures

Structure-Activity Relationships of Different β-Lactam Antibiotics against a Soluble Form of Enterococcus faecium PBP5, a Type II Bacterial Transpeptidase

Penicillin-binding proteins (PBPs) catalyze the essential reactions in the biosynthesis of cell wall peptidoglycan from glycopeptide precursors. beta-Lactam antibiotics normally interfere with this process by reacting covalently with the active site serine to form a stable acyl-enzyme. The design of novel beta-lactams active against penicillin-susceptible and penicillin-resistant organisms will require a better understanding of the molecular details of this reaction. To that end, we compared the affinities of different beta-lactam antibiotics to a modified soluble form of a resistant Enterococcus faecium PBP5 (Delta1-36 rPBP5). The soluble protein, Delta1-36 rPBP5, was expressed in Escherichia coli and purified, and the NH(2)-terminal protein sequence was verified by amino acid sequencing. Using beta-lactams with different R1 side chains, we show that azlocillin has greater affinity for Delta1-36 rPBP5 than piperacillin and ampicillin (apparent K(i) = 7 +/- 0.3 microM, compared to 36 +/- 3 and 51 +/- 10 microM, respectively). Azlocillin also exhibits the most rapid acylation rate (apparent k(2) = 15 +/- 4 M(-1) s(-1)). Meropenem demonstrates an affinity for Delta1-36 rPBP5 comparable to that of ampicillin (apparent K(i) = 51 +/- 15 microM) but is slower at acylating (apparent k(2) = 0.14 +/- 0.02 M(-1) s(-1)). This characterization defines important structure-activity relationships for this clinically relevant type II transpeptidase, shows that the rate of formation of the acyl-enzyme is an essential factor determining the efficacy of a beta-lactam, and suggests that the specific side chain interactions of beta-lactams could be modified to improve inactivation of resistant PBPs.

Microbiology and management of endodontic infections in children.

The first step in the origination of caries is the formation of a dental plaque. Dental caries can lead to destruction of enamel and dentin resulting in bacterial invasion of the pulp. Invasion of the pulp and the periapical areas can promote the development of dento-alveolar abscess and spread of the infection to other anatomical areas. Several oral acid producing aerobic and anaerobic bacteria, including Streptococcus mutans, Lactobacillus acidophilus, and Actinomyces viscosus, are capable of initiating the carious lesion. The organisms that predominate in pulpitis and dento-alveolar abscess are Prevotella, Porphyromonas, Fusobacterium, and Peptostreptococcus spp. Treatment of caries involves removal of all affected tooth structure and proper replacement with a restorative material. Once pulpitis has developed the infected tissue should be removed and root canal therapy instituted, or the tooth should be extracted. Extraction, root canal therapy and/or drainage of pus usually are indicated for an abscess. Antimicrobial therapy supplementing the dental care should be considered, especially when local or systemic spread of the infection is suspected. Penicillin or amoxicillin are generally effective against most of the aerobic and anaerobic bacteria recovered. The patient whose oral cavity may harbor penicillin-resistant organisms should be considered for treatment with drugs effective against these organisms. These agents include amoxicillin-clavulanate, clindamycin or the combination of metronidazole plus amoxicillin or a macrolide.

Management of the Umbilical Cord

After completing this article, readers should be able to: 1. Describe the most serious infection that may result from inappropriate management of the umbilical cord and potential sources. 2. Describe the relationship between infant bacterial colonization and postpartum infection. 3. List the most common neonatal staphylococcal infections. 4. List the factors that affect the timing of cord separation. 5. Delineate the probable causes of drainage from the umbilical stump. This review addresses several aspects of the care of the umbilical cord: how to ligate and cut it, what (if anything) to apply to it, the problems that may be associated with ligation and cutting, and the natural history of cord separation. The traditional method of ligating the umbilical cord was to use string or twine to tie the cord before cutting it. In Southern Sudan, fine stringlike roots are used to tie the cord. More recently in the United States, special cotton tape (umbilical tape) was used and still is found on most trays used for insertion of catheters into umbilical blood vessels. Because the umbilical cord tends to shrink after birth, these types of ligature proved somewhat unreliable in preventing hemorrhage. Although the umbilical arteries tend to constrict rapidly after birth because of the muscular walls, this does not occur with the umbilical vein. Consequently, more efficient and effective methods of ligation were sought in the middle of the 20th century. The first method was to use constricting rubber bands, which were effective, but somewhat difficult to apply. This method recently found favor in a developing country (Ethiopia). However, the more usual method in developed countries currently is plastic or metal clamps, which produce safe, reliable constriction. In particular, the plastic Hollister® clamp (Double-Grip Umbilical Cord Clamp, Hollister, Libertyville, IL) has been very successful in preventing bleeding from the cord. These devices are removed …

Efficacy of azithromycin 1g single dose in the management of uncomplicated gonorrhoea

This paper describes the efficacy of azithromycin 1g single dose in the management of uncomplicated gonorrhoea either with or without chlamydial co-infection. Three hundred and one patients were treated for gonorrhoea between January 2000 and June 2001; 226/301 (75.1%) were treated with azithromycin 1g stat dose while the rest were treated with different regimens. Ninety-seven of 301 (32.2%) of all isolated strains were found to be resistant to at least one antibiotic where penicillin constituted the majority (23%). Chlamydial co-infection was found in 38.2% (115/301). Only 73.1% (220/301) attended for a test-of-cure, all but six patients had negative gonorrhoea cultures at their reviews. Among the six failures 3/32 (9.3%) were initially on amoxicillin, 2/170 (1.2%) on azithromycin and 1/22 (4.5%) on ciprofloxacin. Hence, azithromycin stat dose has proved to be a cost-effective treatment for uncomplicated gonorrhoea supported by the increased prevalence of penicillin-resistant organisms, concomitant chlamydial infection and the high failure rate in keeping review appointments.

The Microbiology and Management of Acute and Chronic Rhinosinusitis.

Although most cases of rhinosinusitis are benign, the disruption of quality of life due to disease symptoms leads patients to seek early medical care. Ongoing debates dispute the definition, bacteriology, and medical management of chronic sinusitis, while the criteria for acute sinusitis are relatively well established. Chronic rhinosinusitis remains poorly categorized, and authors differ in opinions of symptoms, time course, and bacteriology of the infections, as well as proper medical management. Recent studies from the Mayo Clinic even question the idea that chronic sinusitis is a bacterial disease and document the presence of fungal pathogens that are responsible for the inflammatory reaction and mucosal response. In general, medical management is based on physiologic principles of re-establishing natural mucociliary function and restoring proper aeration of the paranasal sinuses after an inflammatory insult. Injudicious use and indiscriminate overprescription of antibiotics has fostered the rapid development of penicillin-resistant organisms over the past two decades. Drug-resistant Streptococcus pneumonia and b-lactamase-producing Haemophilus influenzae and Moraxella catarrhalis are becoming the norm, forcing the need to consider alternatives in antibacterial management. Appropriate medical management of this common problem requires a systematic approach and consideration of adjunctive therapy. This article examines the current bacteriology of these common infections and reviews the management of acute and chronic infections.

Invasive pneumococcal disease in homozygous sickle cell disease: Jamaican experience 1973-1997

Objectives: To examine the clinical features and epidemiology of invasive pneumococcal disease in homozygous sickle cell (SS) disease and the efficacy of pneumococcal prophylaxis. Study design: A retrospective study of 80 episodes in 68 patients in the Jamaican Sickle Cell Clinic in a 25-year period (1973-1997). Results: Clinical features included a history of fever (94%), vomiting (70%), an ill appearance (80%), fever (89%), abnormal chest signs (43%), and meningismus (39%). There were 14 deaths—13 among 68 initial episodes (6 of which were deaths on arrival) and one death during a recurrence. Thirteen episodes occurred in patients who should have been receiving antibiotic prophylaxis. Ten were due to failure to adhere to protocols, and 3 occurred during prophylaxis; one patient was receiving oral erythromycin, and two had received injections of benzathine penicillin 4 and 24 days before the episode. All but one of the pneumococcal isolates were susceptible to penicillin. The 32 patients who received pneumococcal vaccine had more mild clinical courses as indicated by a greater chance of being treated as outpatients or surviving after admission (Mann-Whitney U test, P =.03). Conclusions: Penicillin remains the mainstay of prophylaxis, although breakthroughs occur and will become more common with the increasing frequency of penicillin-resistant organisms. Pneumococcal immunization appears to ameliorate the course of invasive disease. (J Pediatr 2001; 138:65-70)

Antibiotic resistance and therapeutic options in lower respiratory tract infections

The emergence of some strains of common pathogens of community acquired pneumonia resistant to one or more of the frequently used antimicrobials is becoming widespread. The clinical significance and implications of these resistance patterns are, however, unclear. Studies of the clinical progress of patients with pneumonia or bacteraemia infected with penicillin-resistant organisms show that patients frequently recover when treated with penicillins or cephalosporins. β-Lactam drugs and macrolides are still associated with clinical success in lower respiratory tract infections despite increasing resistance to these agents in vitro. Therefore, when making therapeutic choices, in vitro resistance data cannot always be used to predict clinical outcome. Infections caused by resistant organisms can usually be successfully treated using traditional therapeutic approaches.

MICROBIOLOGY OF COMMON INFECTIONS IN THE UPPER RESPIRATORY TRACT

The management of upper respiratory tract infections has become more difficult because of the recent increase in the number of penicillin-resistant organisms. The bacteria that predominate in otitis media and sinusitis can resist penicillin through the production of the enzyme beta-lactamase (Haemophilus influenzae and Moraxella catarrhalis in acute infections and Staphylococcus aureus and Prevotella and Fusobacteria spp in chronic infections) or through changes in penicillin-binding sites (Streptococcus pneumoniae). beta-lactamase-producing bacteria can express their pathogenicity directly through their ability to cause infections and indirectly by production of the enzyme, thus protecting penicillin-susceptible pathogens from penicillins. This phenomenon may explain penicillin's failure in the treatment of Group A beta-hemolytic streptococcal (GABHS) tonsillitis. An additional cause for penicillin failure is the absence among the normal tonsillar bacterial flora of streptococcal species that are capable of interfering with the growth of GABHS. Proper use of antimicrobial therapy, including those therapies that are effective against penicillin-resistant bacteria, is the cornerstone of management of upper respiratory tract infections.

Monthly changes in the rate of recovery of penicillin-resistant organisms from children.

Monthly changes in the rate of recovery of penicillin-resistant organisms from children.

Comparative trial of 3-day azithromycin versus 10-day amoxycillin/clavulanate potassium in the treatment of children with acute otitis media with effusion

A randomized, open clinical trial was performed to compare azithromycin and amoxycillin/clavulanate potassium in children with acute otitis media with effusion. Patients were allocated to therapy with azithromycin (10 mg/kg once daily for 3 days) or amoxycillin/clavulanate potassium (40 mg/kg/day divided into three equal doses for 10 days). Clinical examination and tympanometric evaluation were performed at baseline, and at day 3 to 5, day 10 to 14, day 28 to 30 and day 55 to 60 after the initiation of therapy. Tympanocentesis fluid cultures were collected at enrolment, and urine and blood samples were obtained at baseline and at day 10 to 11. Of 100 patients enrolled, 92 were considered evaluable. Middle ear cultures were positive in 53.2% of the patients; the most common pathogens were Streptococcus pneumoniae (33%) and Haemophilus influenzae (33%). The response was satisfactory in 47 (100%) patients treated with azithromycin and 42 (95.4%) patients receiving A/C. Rates of persistence of middle ear effusion were comparable. Nausea and loose stools were more common in children treated with amoxycillin/clavulanate potassium ( P ≤ 0.02). Based on the comparable efficacy noted in this study, the lower incidence of side-effects and the convenience of a shorter duration of treatment, azithromycin represents an attractive therapeutic alternative to amoxycillin/clavulanate potassium and should be further evaluated in larger-scale clinical trials including patients with penicillin-resistant organisms.

Microbial dynamics of persistent purulent otitis media in children

Repeated aspirations (for a period of 36 to 55 days) of the exudate through an open perforation were performed in seven children with acute otitis media that did not respond to antimicrobial therapy. Penicillin-resistant organisms were present in all but one of the first two aspirates. Failure to respond to antimicrobial therapy was associated with the emergence of resistant anaerobic and aerobic bacteria in the third and fourth cultures. The infection was cured in all instances after administration of antimicrobial agents effective against these bacteria. (J P EDIATR 1996;128:237-40)

The microbiology and antibiotic treatment of peritonsillar abscesses

Pus from 53 peritonsillar abscesses was cultured and associations between the microbiological results and clinical data were investigated with the aim of developing a clinical protocol for treatment. A positive culture grew in 85% of quinsies and of these 16% produced aerobes and 84% anaerobes. Penicillin-resistant organisms were grown from 32% of patients and all but one of these organisms (Haemophilus influenzae) was sensitive to metronidazole. There was no association between clinical presentation and cultured organism which could guide treatment, hence we recommend penicillin and metronidazole as the antibiotic regimen of choice in the treatment of peritonsillar abscesses because of its effectiveness in 98% of patients.

Gonococcal arthritis in an era of increasing penicillin resistance. Presentations and outcomes in 41 recent cases (1985-1991).

To assess the impact of recent reports of disseminated gonococcal infection caused by penicillin-resistant organisms, we reviewed the presenting features, clinical course, and outcomes of a group of patients with gonococcal arthritis treated in recent years. We reviewed the records of all cases of acute arthritis associated with a culture positive for Neisseria gonorrhoeae at our institution from July 1985 through December 1991. Forty-one cases were identified. Patients included 34 women and 38 blacks; the mean age was 22.6 years. Duration of symptoms averaged 4.8 days at presentation. Other features included migratory arthralgias (n = 27), urogenital symptoms or signs (n = 26), fever (n = 21), and skin lesions (n = 16). Comorbid conditions included intravenous drug use (n = 8) and systemic lupus erythematosus (n = 3). The knee was the most commonly affected joint. Positive culture results were obtained from 32 urogenital samples (86%), 14 synovial fluid samples (44%), seven rectal samples (39%), four blood samples (12%), and two throat samples (7%). All synovial fluid samples with positive culture results had white blood cell counts higher than 20.0 x 10(9)/L. Response to therapy with penicillin and/or ceftriaxone was prompt, and mean duration of hospitalization was 5.8 days. Patients who required longer hospitalization had a higher mean erythrocyte sedimentation rate and higher frequencies of positive synovial fluid culture results and comorbid conditions. Penicillin sensitivity could be determined in 30 patients on the basis of clinical response or in vitro testing. Among these patients, two cases of penicillin-resistant organisms were identified, one beta-lactamase positive and one beta-lactamase negative. The clinical features of patients with gonococcal arthritis have changed very little since the last large reported series over a decade ago. Underlying conditions appear to be more common, but response to antibiotic therapy and eventual outcome remain excellent. The finding of penicillin-resistant organisms in at least 5% of patients reinforces recent recommendations that third-generation cephalosporin agents be used as initial therapy for disseminated gonococcal infections until drug susceptibilities are known.