Ran Nir-Paz

Group G Streptococcal Bacteremia in Jerusalem

Recurrent group G Steptococcus bacteremia, associated with lymphatic disorders and possibly emm stG840.0, is described.

Prophage excision activates Listeria competence genes that promote phagosomal escape and virulence.

The DNA uptake competence (Com) system of the intracellular bacterial pathogen Listeria monocytogenes is considered nonfunctional. There are no known conditions for DNA transformation, and the Com master activator gene, comK, is interrupted by a temperate prophage. Here, we show that the L. monocytogenes Com system is required during infection to promote bacterial escape from macrophage phagosomes in a manner that is independent of DNA uptake. Further, we find that regulation of the Com system relies on the formation of a functional comK gene via prophage excision. Prophage excision is specifically induced during intracellular growth, primarily within phagosomes, yet, in contrast to classic prophage induction, progeny virions are not produced. This study presents the characterization of an active prophage that serves as a genetic switch to modulate the virulence of its bacterial host in the course of infection.

Deep Infection by Trichophyton rubrum in an Immunocompromised Patient

ABSTRACT Dermatophytes are common pathogens of skin but rarely cause invasive disease. We present a case of deep infection by Trichophyton rubrum in an immunocompromised patient. T. rubrum was identified by morphological characteristics and confirmed by PCR. Invasiveness was apparent by histopathology and immunohistochemistry. The patient was treated successfully with itraconazole.

Macrolide Resistance in Mycoplasma pneumoniae, Israel, 2010

Macrolide resistance in Mycoplasma pneumoniae is often found in Asia but is rare elsewhere. We report the emergence of macrolide-resistant M. pneumoniae in Israel and the in vivo evolution of such resistance during the treatment of a 6-year-old boy with pneumonia.

Identification of Risk Factors for Infection in an Outbreak of Mycoplasma pneumoniae Respiratory Tract Disease

BACKGROUND Mycoplasma pneumoniae is one of the most common pathogens that causes community-acquired respiratory tract infection. Outbreaks are well known, and all age groups are susceptible. An outbreak in an army training unit afforded an opportunity to identify possible risk factors for morbidity. METHODS An outbreak of respiratory illness that occurred in a unit comprising 91 trainees was investigated and analyzed as a cohort study. M. pneumoniae infection was suspected on clinical grounds and was confirmed by polymerase chain reaction, culture, and serologic testing. Data regarding medical history, symptoms, signs, and laboratory tests were collected. RESULTS During a period of 12 days, 41 soldiers (45.1%) had respiratory illnesses, of which 10 (11.0%) were pneumonia. Comparison of symptomatic and asymptomatic individuals revealed that smoking was associated with higher rates of disease (risk ratio, 2.1; 95% confidence interval [CI], 1.3-3.2; P<.005) and seroconversion (risk ratio, 2; 95% CI, 1.2-3.4; P=.03). In multivariate analysis, both lower acute immunoglobulin G values (adjusted odds ratio, 7.8; 95% CI, 1.4-42.5; P=.018) and smoking (adjusted odds ratio, 5.6; 95% CI, 1.5-20.4; P=.01) were associated with symptomatic infection; stratification according to smoking status revealed that immunoglobulin G levels among nonsmokers were protective. Patients who had pneumonia had lower lymphocyte counts (1400+/-258 vs. 2000+/-465 cells/microL; P=.001). CONCLUSIONS Smoking and lower preexisting immunoglobulin G levels were strongly associated with M. pneumoniae respiratory infection. These findings emphasize the importance of immunity and cessation of smoking for the prevention of disease. The high attack rate emphasizes the extent of infection transmission among healthy persons living in close contact.

The spread of Mycoplasma pneumoniae is polyclonal in both an endemic setting in France and in an epidemic setting in Israel.

Mycoplasma pneumoniae infections occur both endemically and epidemically, and macrolide resistance has been spreading for 10 years worldwide. A substantial increased incidence of M. pneumoniae infections has been reported in several countries since 2010. Whether this increased incidence is attributed to different or to the same M. pneumoniae genotype is unknown. We have developed a multilocus variable-number tandem-repeat (VNTR) analysis (MLVA) for the molecular typing of M. pneumoniae isolates. In this study, the MLVA typing method was modified and validated to be applicable directly to respiratory tract specimens without culture. This method was applied to 34 M. pneumoniae-positive specimens received at the Bordeaux Hospital, France, between 2007 and 2010 in an endemic setting, and to 63 M. pneumoniae-positive specimens collected during an epidemic surge of M. pneumoniae infections in 2010 in Jerusalem, Israel. The M. pneumoniae endemic spread was shown to be polyclonal in France, with 15 MLVA types identified. Strikingly, the Israeli epidemic surge was also a multi-clonal phenomenon, with 18 circulating MLVA types. The macrolide resistance-associated substitution, A2058G, was found in 22% of the Israeli patients. Macrolide-resistant M. pneumoniae belonged to four MLVA types, the MLVA type Z being the most frequent one. An association between the MLVA type Z and macrolide resistance might exist since macrolide resistance was present or generated during the course of illness in all patients infected with this MLVA type. In conclusion, the discriminatory power of the MLVA showed that the spread of M. pneumoniae strains in France in an endemic setting was polyclonal as well as the surge of M. pneumoniae infections in Israel in 2010.

Clinical and Epidemiological Aspects of Infections Caused by Fusarium Species: a Collaborative Study from Israel

ABSTRACT Fusarium infections are an important problem worldwide, commonly affecting immunocompromised individuals. We conducted a retrospective study in two Israeli tertiary medical centers of factors predisposing to infection by Fusarium spp. and their influence on the epidemiology and clinical outcome of this infection. Fusarium spp. were isolated from 89 patients with a median age of 57 years. Sixty-eight patients were considered immunocompetent. Seven patients had disseminated disease, 34 had locally invasive disease, and 48 had superficial infection. Most infections were limited and occurred mainly in lower limbs. Factors associated with in-hospital mortality were chronic renal failure, hematological malignancy, immunosuppression, disseminated infection, and positive blood culture. Multivariate analysis showed that chronic renal failure, hematological malignancy, burns, and disseminated infection were independently associated with mortality. A surge in the frequency of infections was noticed during the summer for patients from rural areas, involving mainly the eyes and lungs. At one of the hospitals (in a mountainous area), there was an increase in the isolation rate over time.

emm Typing of M Nontypeable Invasive Group A Streptococcal Isolates in Israel

ABSTRACT We performed emm typing of M nontypeable invasive group A streptococcal (GAS) isolates collected in a prospective population-based study in Israel. One hundred twenty of 131 isolates (92%) had emm sequences compatible with GAS, consisting of 51 different emm types. Eleven isolates were found to be group G streptococcus. Of the 120 isolates, 55 (46%) belonged to 32 types for which there were no typing sera available in the Streptococcal Reference Laboratory in Israel. The other 65 (64%) isolates, consisting of 19 types, had sera available and therefore could have been serotyped. Forty-three isolates had T and emm types which were not correlated according to standard M-typing protocols and were therefore missed. The principal effect of emm typing was the addition of 32 types not previously identified in Israel and the discovery of new associations between emm and T types. emm typing did not significantly change the proportion of M types; the five most common types were 3, 28, 2, 62, and 41. Twenty different types comprised 80% of all isolates. No new emm sequences were discovered. emm typing emphasized the unusually low incidence of M1 strains causing severe disease in Israel. As serological typing of GAS becomes more problematic due to lack of sera and the appearance of new emm types, reference laboratories should replace M typing with emm sequence typing. Development of a GAS vaccine relies on the emm type distributions in different geographical locations. In our study, 7% of isolates (types 41 and 62) are not included in a 26-valent vaccine that is being studied.

Compound Cardiac Toxicity of Oral Erythromycin and Verapamil

OBJECTIVE: To report a case of complete atrioventricular (AV) block and QTc prolongation following coadministration of high-dose verapamil and erythromycin. CASE SUMMARY: A 79-year-old white woman was admitted to the hospital due to extreme fatigue and dizziness. On admission, heart rate was 40 beats/min and blood pressure was 80/40 mm Hg. An electrocardiogram showed complete atrioventricular (AV) block, escape rhythm of 50 beats/min, and QTc prolongation 583 msec. This event was attributed to concomitant treatment with verapamil 480 mg/d and erythromycin 2000 mg/d, which was prescribed one week before admission. DISCUSSION: This is the first case published describing complete AV block and prolongation of QTc following coadministration of erythromycin and verapamil. CYP3A4 is the main isoenzyme responsible for metabolism of erythromycin and verapamil. Both drugs are potent inhibitors of CYP3A4 and of P-glycoprotein; this may be the basis for the pharmacokinetic interaction between erythromycin and verapamil. In addition to being a woman, our patient had other risk factors for QT prolongation: slow baseline heart rate (probably induced by verapamil), left-ventricular hypertrophy, and possibly ischemic heart disease. CONCLUSIONS: This life-threatening arrhythmia was probably the result of a pharmacokinetic and/or pharmacodynamic interaction of high-dose verapamil and erythromycin.

Unusual presentation of familial Mediterranean fever: role of genetic diagnosis

OBJECTIVE To describe the role of molecular analysis in the diagnosis of an unusual presentation of familial Mediterranean fever (FMF). CASE REPORT Two patients presenting with prolonged fever without signs and symptoms of serositis are described. FMF was diagnosed by genetic analysis, which disclosed that both patients were homozygous for the M694V mutation of the Mediterranean fever (MEFV) gene. CONCLUSION Molecular analysis of FMF should complement the investigation of patients with fever of unknown origin. This test enables a definite diagnosis of the disease and may promote the diagnosis and treatment of patients with an unusual or incomplete clinical picture of FMF.