Ethan Rubinstein

Nasopharyngeal Carriage of Streptococcus pneumoniae by Adults and Children in Community and Family Settings

The rate of Streptococcus pneumoniae carriage among adults was compared with that among children (age, < or =6 years) in the same population. Nasopharyngeal culture results for 1300 adults and 404 children were analyzed. S. pneumoniae was carried by only 4% of the adults, compared with 53% of children in the same community. Young age, day care center attendance, having young siblings, and no antibiotic use during the month before screening were associated with the high carriage rate among children, whereas the only risk factor associated with carriage among adults was the presence of a respiratory infection on the screening day. S. pneumoniae serotype distribution and antibiotic resistance patterns differed between adults and children. Isolates of the same serotype--even of the same clone--differed in their antibiotic susceptibility patterns between children and adults. In a subanalysis of 151 pairs of children and their parents and of 32 pairs of siblings, intrafamilial transmission of S. pneumoniae could not be demonstrated.

History of quinolones and their side effects.

Fluoroquinolone development from 1985 to the present was reviewed. Severe drug adverse events were noted for enoxacin, pefloxacin and fleroxacin, which were phototoxic. Temafloxacin was associated with severe hemolytic–uremic syndrome, lomefloxacin caused phototoxicity and central nervous system (CNS) effects, and sparfloxacin was associated with phototoxicity and QTc prolongation. Tosufloxacin caused severe thrombocytopenia and nephritis, and hepatotoxicity was reported for trovafloxacin. Grepafloxacin was withdrawn due to cardiovascular effects, and clinafloxacin was associated with phototoxicity and hypoglycaemia. The structure of the quinolones directly relates to both their activity and side-effect profiles. The relationship among specific substituents attached to the quinolone nucleus are clarified. The incidence of specific adverse events associated with individual fluoroquinolones was reviewed in a five-year post-marketing surveillance (PMS) study in Japan, in which a total adverse drug reaction (ADR) rate of 1.3% was found for levofloxacin, compared to total ADR rates of 3.3% for pazufloxacin, 3.6% for tosufloxacin, 4.5% for gatifloxacin and 5.4% for balofloxacin. Gastrointestinal effects were the most common adverse events for all fluoroquinolones. Levofloxacin had the lowest rate of CNS effects and skin adverse events among the agents listed.

Quinolones, theophylline, and diclofenac interactions with the gamma-aminobutyric acid receptor.

Epileptic seizures and hallucinations, which are rare in patients receiving quinolones, have been observed more frequently in patients receiving both quinolones and either theophylline or nonsteroidal anti-inflammatory drugs. Inhibition of gamma-aminobutyric acid (GABA) binding to the GABA receptor, resulting in general excitation of the central nervous system, may be the underlying mechanism of these adverse phenomena. We demonstrate here that ciprofloxacin displaced a GABA-like substance (muscimol) from the GABA receptor when administered in concentrations of greater than 10(-4) M. These concentrations were lower than those needed by pefloxacin, ofloxacin, and nalidixic acid to reach a concentration that inhibits 50% of binding. The combination of ciprofloxacin and theophylline was additive in reducing the level of muscimol binding to the GABA receptor, whereas a diclofenac-ciprofloxacin combination had no effect. The concentrations of both ciprofloxacin and the other quinolones used were much higher than those observed in human serum and cerebrospinal fluid in a clinical setting; however, different human GABA receptor affinities, preexisting GABA excitation, or underlying central nervous system disease may amplify the excitatory side effects observed by the co-administration of quinolones and theophylline. Attention should be paid to the possible epileptogenic activity of the simultaneous administration of quinolones with aminophylline, nonsteroidal anti-inflammatory drugs, or other unpredictable drugs.

Prediction of creatinine clearance from serum creatinine concentration based on lean body mass

An equation for predicting endogenous creatinine clearance (CrCl) in adults and children (with both stable and unstable renal function) from serum creatinine concentrations is presented. The predictions are compared with four other available estimating methods, based on values in 110 subjects with renal impairment of widely differing degrees. In patients with stable and with unstable renal function the correlation between measured and predicted CrCl was better with the new equation. In patients with rapidly changing renal function the new equation resulted in accurate predictions of CrCl within a few hours after the change, as opposed to several days with the other methods. The elimination rate constant of the aminoglycoside antibiotic amikacin correlated more precisely with CrCl values estimated from the new equation than with those measured during 24 hr or with the other prediction methods.

An outbreak of Phialemonium infective endocarditis linked to intracavernous penile injections for the treatment of impotence.

BACKGROUND In March 2002, a patient in Tel Aviv, Israel, died of endocarditis caused by Phialemonium curvatum. As part of his therapy for erectile dysfunction, the patient had been trained to self-inject a compound of vasoactive drugs provided by an impotence clinic into his penile corpus cavernosous. METHODS We identified the used prefilled syringes as the source of his infection. Similar cases were investigated as a putative outbreak of P. curvatum invasive disease among customers of this impotence clinic. P. curvatum isolates, cultured from samples obtained from the patients and from prefilled syringes, were compared by DNA sequencing of the nuclear ribosomal internal transcribed spacer. RESULTS We identified 2 additional customers at the impotence clinic who had P. curvatum endocarditis. In addition, cultures of unused, prefilled syringes and bottles provided by the same clinic to 5 asymptomatic customers tested positive for pathogenic molds (P. curvatum in 4 cases and Paecilomyces lilacinus in 1). All P. curvatum isolates were of a single genetic type that is known only from this outbreak but is closely related to 3 other P. curvatum genotypes associated with pathogenicity in humans. CONCLUSIONS P. curvatum is an emerging pathogen that can be readily isolated from blood. We identified an outbreak of P. curvatum endocarditis among men who had erectile dysfunction treated by intracavernous penile injections from contaminated prefilled syringes.

Prevalence and genetic relatedness of community-acquired methicillin-resistant Staphylococcus aureus in Israel

The aims of the study presented here were to determine the prevalence of Staphylococcus aureus carriage and, specifically, community-acquired methicillin-resistant S. aureus (CA-MRSA) carriage in children and their parents in Israel and to determine the genetic relatedness of these isolates. S. aureus was isolated from 580 of 3,373 (17.2%) individuals screened. The predominant type identified by pulsed-field gel electrophoresis was strain ST45-MSSA (25%). Five MRSA isolates were detected, and two of these were classified as CA-MRSA, based on the following criteria: no previous contact with a healthcare facility, absence of a multidrug-resistant (MDR) phenotype, and presence of SCCmec type IV. Isolates were negative for pvl and were classified as ST-45-MRSA. Although CA-MRSA is still rare in Israel, the genetic relatedness of the strains found in this study to a successful MSSA clone warrants close follow up.

Future Prospects and Therapeutic Potential of Streptogramins

SummaryDramatic changes in the epidemiology and susceptibility patterns of Gram-positive cocci during the last decade have mandated new approaches to the management of many bacterial infections. For example, there has been a sharp increase in the incidence of infections caused by Staphylococcus aureus, particularly those resistant to methicillin (MRSA), and methicillin-resistant coagulase-negative staphylococci, particularly those associated with foreign bodies and indwelling medical devices. Additionally, the worldwide spread of Streptococcus pneumoniae strains resistant to penicillin and macrolides, and the emergence of enterococci (particularly Enterococcus faecium) resistant to vancomycin, teicoplanin and other antibiotics, present further therapeutic problems.New antibacterial agents are urgently required to meet the challenges posed by these epidemiological trends. The semisynthetic streptogramins, a unique class of antibacterials currently under development, offer promise in the treatment of such multiresistant infections. Possible future applications include treatment of infections caused by the following organisms: MRSA, enterococci resistant to vancomycin, macrolides or lincosamides; and β-lactam-resistant streptococci. They may also prove useful as therapy for children with staphylococcal infection and patients with multiresistant infections who are unable to tolerate vancomycin, including patients with skin and soft tissue infections caused by Gram-positive pathogens, patients with osteomyelitis, foreign body associated infections, endocarditis and sepsis due to Gram-positive bacteria. Clinical trials are required to evaluate the efficacy and tolerability of streptogramins in these settings.

In Vitro Activity of Cinoxacin, Ampicillin, and Chloramphenicol Against Shigella and Nontyphoid Salmonella

The in vitro antibacterial activity of cinoxacin was compared with that of ampicillin and chloramphenicol against 26 strains of nontyphoid Salmonella and 44 strains of Shigella. Cinoxacin was found to have a lower minimal inhibitory concentration than ampicillin and chloramphenicol against all Salmonella and Shigella sonnei strains. Cinoxacin had minimal inhibitory concentrations similar to those of chloramphenicol but lower than those of ampicillin against Shigella flexneri and S. boydii strains.

Prevention of Infections During Neurosurgery

Infections associated with neurosurgery can be disastrous. Ample evidence supports the routine use of prophylactic antibacterials in clean, nonimplant neurosurgical procedures to reduce the risk of wound infections. A recently performed meta-analysis suggests that even in neurosurgical units that do not use antibacterial prophylaxis and have a low wound infection rate, prophylaxis may still be beneficial. Since comparative studies are lacking, selection of one prophylactic regimen over another is somewhat arbitrary. In neurosurgical units where the prevailing pathogens are still antibacterial-sensitive Gram-positive cocci, the regimen selected should be aimed at these pathogens. Antistaphylococcal antibacterials, of which the most frequently studied agents are various first or second generation cephalosporins, are suitable for this purpose. Future studies should compare proposed new antibacterial regimens with one of those already demonstrated to be effective.In clean-contaminated nonimplant neurosurgery, recommendations for antibacterial prophylaxis are currently based on theory only. We suggest use of the same prophylactic regimens as those used for clean, nonimplant neurosurgery.In shunt implant procedures, the efficacy of antibacterial prophylaxis has not been proven convincingly. Prophylaxis may be warranted in neurosurgical units with high baseline infection rates. For prevention of external wound infection, an anti-Gram-positive agent is recommended. For prevention of the more important internal shunt-infection, new strategies involving devices with antimicrobial and antiadherence properties are needed.The timing of administration of the prophylactic agent is crucial for its protective effect. The appropriate agent should therefore be administered 30 to 60 minutes before skin incision. For longer procedures and when using antibacterials with a short half-life, repeated intraoperative administration is required. Administration of antibacterial prophylaxis after closure of the wound incision has no proven benefit and is strongly not recommended.

A Review of the Adverse Events Profile of Cefpirome

SummaryCefpirome is a new fourth generation injectable cephalosporin antibiotic. Its tolerability profile was established in a programme of 16 clinical studies involving 3103 patients in Europe and the US. The overall incidence of clinical adverse events with cefpirome was 21.9% compared with 27.1% with comparators (ceftazidime, imipenem, ceftriaxone). Adverse events thought possibly related to treatment occurred in 12.5% of patients receiving cefpirome and 13.7% of recipients of comparator agents. Withdrawals from treatment due to adverse events occurred in 5.1 and 5.0% of patients receiving cefpirome and comparators, respectively. The commonest adverse events thought possibly related to treatment were gastrointestinal symptoms (mainly diarrhoea in 1.6 and 1.7%, respectively) and rash (1.4 and 1.4%, respectively). Comparison with data obtained from the literature for ceftazidime, ceftriaxone and the third generation cephalosporins in general shows that the adverse event profile of cefpirome is similar to that of other broad-spectrum injectable cephalosporins.