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Mycoplasma pneumonia is responsible for multisystemic infection. Pulmonary symptoms are most common in children. We describe herein two unusual severe forms of M. pneumoniae infection without initial pulmonary symptoms. The first case is an 8-month-old boy who was hospitalized in the pediatric intensive care unit with severe sepsis. There were no initial pulmonary symptoms, nor obvious clinical infection. Initial blood tests and x-ray did not aid the diagnosis. The blood tests came back positive for M. pneumonia. Pulmonary symptoms eventually appeared 24h later, and there was a pneumonia outbreak on the chest radiograph. The boy was given josamycin and improved quickly. The second case concerns an 8-year-old child who was hospitalized in the pediatric intensive care unit with toxic shock. No clinical infectious origin was found. A broad-spectrum antibiotic therapy was started with ceftriaxone and josamycin. The M. pneumoniae blood test came back positive, which confirmed the diagnosis of septic shock in M. pneumoniae, requiring adjustment of the antibiotic therapy. Current guidelines for the choice of probabilistic antibiotic therapy in case of severe sepsis do not include the case of M. pneumoniae. The early initiation of antibiotic therapy plays a major role in the prognosis of these patients. It seems useful to search for M. pneumoniae in cases of severe atypical infections, particularly in the absence of pulmonary symptoms.

SENLAT syndrome, also known as TIBOLA/DEBONEL, is an emerging disease in France. The major symptoms are necrotic eschar on the scalp associated with painful cervical lymphadenopathy. It occurs mainly in women and children during the cold seasons after a bite by a Dermacentor tick, responsible for transmitting Rickettsia slovaca or Rickettsia raoultii. Cutaneous swabs are safe, easy and reliable tools that should be used routinely by physicians to confirm diagnosis. In this particular disease, they should be preferred to serology, which is less sensitive. Doxycycline is the antibiotic of choice for this syndrome.

Digitalis intoxication is usually accidental in children. We report the case of a young infant with congenital heart disease in whom the coadministration of digoxin and josamycin led to a 50% increase in the digoxin concentration, generating sinoatrial block and cardiac failure. Clinical and electrocardiographic symptoms very quickly resolved following immunotherapy with antidigitalis Fab fragments. Digoxin concentrations must be carefully monitored in patients concomitantly receiving macrolides to ensure that the digoxin dose can be readjusted if necessary.

In this randomized open study, 325 children aged two to 15 years with acute tonsillitis and a positive test of GA beta H streptococcal antigen were treated with josamycin 50 mg.kg-1.day-1 b.i.d for 5 days, or penicillin 50,000 to 100,000 IU/day t.i.d for 10 days. Clinical assessments and throat cultures for GA beta HS isolation were performed at the inclusion visit (V1), at the end of treatment visit (V2: day 12 for all patients) and at the follow-up visit (V3: day 30). In case of positive GA beta HS culture, the bacterial DNA by RFLP was performed to differentiate between the persistence (presence of original strain at V2), relapse (eradication at V2 and acquisition of same strain at V3) and reinfection (eradication at V2 and acquisition of different strain at V3).Two hundred and twenty-three patients were included in the bacteriological and clinical criteria per protocol analysis. At V2, eradication rates were comparable: 82% in josamycin and 80% in penicillin patients; clinical cure rates were 90% and 89%. At V3, relapse of GAS assessed only on clinically and bacteriologically cured patients at V2 occurred in 12% of josamycin patients and 12.8% of penicillin patients. Tolerance was good; 14% and 10% of josamycin and penicillin patients respectively experienced an adverse event.In this non-inferiority study, the efficacy of a 5-day course of josamycin is comparable to reference treatment in GA beta HS tonsillitis in children.

The in vitro susceptibility of Ureaplasma urealyticum (Uu) and Mycoplasma hominis (Mh) was evaluated in a multicentric study performed in seven hospitals from different geographic areas in France. During a three month period, 324 Uu and 72 Mh clinical isolates were tested using a system ready for use, SIR Mycoplasma (Sanofi Diagnostics Pasteur). For Uu, the percentage of strains intermediate (I) or resistant (R) was as follows: doxycycline (3), minocycline (2.5), lymecycline (6.7), erythromycin (72, most I), josamycin (0.9), clindamycin (88), pristinamycin (0.3), ofloxacin (34, most I). For Mh, the percentage of strains I or R was respectively: doxycycline (2.7), minocycline (5.5), lymecycline (15.2), erythromycin (100), clindamycin (1.4), ofloxacin (2.7), josamycin (0) and pristinamycin (0). Comparable results were observed in the different geographic areas. The frequency of acquired resistances does not justify modifications in the usual treatment of genital mycoplasma infections but leads to monitor their susceptibility to antibiotics.

Bacillary angiomatosis is a newly recognized multisystem opportunistic infection seen in the human immunodeficiency virus infection. The disease is marked by papular and nodular vascular skin lesions that clinically resemble Kaposi's sarcoma. Histologically, the lesions are different and show clusters of bacteria showing the structure of Gram negative bacilli staining with Warthin-Starry stain. Transmission electron microscopy shows that the organisms (1 to 2 microns) have a trilamellar wall structure. Treatment with oral erythromycin (2 to 3 g a day) for 2 to 4 weeks rapidly leads to resolution.

Betalactamase-producing organisms are responsible for an increasing number of ENT and lower respiratory tract infections. Or cephalosporins and the combination of amoxicillin with the beta-lactamase inhibitor clavulanic acid are alternatives to ampicillin therapy. The killing activity of cefadroxil on the organisms most often responsible for ENT and respiratory infections was evaluated in vitro using a viable bacteria count method, comparatively with cefaclor, josamycin, and amoxicillin-clavulanic acid. Killing activity was found to be time-dependent for all the antimicrobial agents studied. Cefadroxil exhibited the same bactericidal effect on Streptococcus pyogenes and S. pneumoniae than the other agents. Haemophilus influenzae and an increasing number of Pneumococcus strains were resistant to josamycin which is therefore not appropriate for first-line therapy. As compared with amoxicillin and amoxicillin-clavulanic acid, cefadroxil was less active on H. influenzae and more active on Staphylococcus aureus. Production of beta-lactamase failed to influence the killing activity of cefadroxil. These bacteriologic data, together with results of pharmacologic studies (long half-life and good penetration within tissues) can explain the clinical successes obtained with cefadroxil in ENT and lower respiratory tract infections.

In an open, multicenter randomized clinical trial on patients with acute pneumonia, 5-day therapy using a new oral macrolide antibiotic, azithromycin (Az), was compared with standard 10-day therapy using another macrolide, josamycin (J). Eighty-nine patients were treated (46 Az, 43 J); both groups were comparable, except in terms of the sex ratios. The causative agent was determined in 31 cases; streptococcal pneumonia was the most common diagnosis (48%). Cure rates were 93% for J and 80% for Az (p greater than 0.30), as judged by a fall in body temperature and an improvement in clinical condition and in radiographic findings. Among 6 failures, there were 4 cases of empyema (1 J, 3 Az). Of 6 deaths, 2 were pneumonia-dependent (1 J and 1 Az, Haemophilus and Streptococcus pneumoniae, respectively). We conclude that 5-day Az is as effective as 10-day J and that such short-course therapy is an advantage in the treatment of pneumonia caused by macrolide susceptible pathogens.

We have previously reported that josamycin (JM) displayed a bactericidal synergy with human neutrophils (PMN) in vitro without altering significantly various cell functions (Labro et al., Path. Biol., 1989, 37, 329-334). Since JM may concentrate into phagocytes, and partly at least into lysosomes, it was of interest to analyze if the presence of this molecule could enhance the bactericidal activity of some acellular systems mimicking those acting inside the phagolysosome, using Staphylococcus aureus as the bacterial target. Erythromycin (EM) was assessed comparatively. While none of the macrolides increased the lethal effect of a crude PMN extract (02-independent system), an enhancement of the bacterial killing by an oxidant stress was observed in the presence of the 2 molecules. However, the effect of JM was strongest that the one induced by EM: S. aureus survival after exposure to xanthine + xanthine oxidase was 38 +/- 17.2% and it was reduced to 11 +/- 5.0 and 23 +/- 15.6 with JM (30 and 3 mg/l) and 22 +/- 13.1 and 23 +/- 9.7 with EM (30 and 3 mg/l). On the other hand, S. aureus survival after exposure to H2 O2 was reduced only by JM (16 +/- 9.4 and 32 +/- 6.9% versus 43 +/- 11.2% for controls). Pretreatment of S. aureus for 60 min by JM or EM did not alter the sensitivity of the bacteria either to PMN or to acellular systems. These data suggest that JM (and at a lesser degree EM) could be transformed by reactive oxygen species generated inside the phagolysosome to become more toxic for the bacteria.(ABSTRACT TRUNCATED AT 250 WORDS)

Atropine derivatives. The presence of atropine derivatives in numerous combined medicines is often ignored or reflected. A case report of prolonged bilateral non reactive mydriasis with "cycloplegia", linked with the utilisation of a therapeutic dose of Lameline suppositories raises the question of individual susceptibility, with particular ocular sensitivity. This urge one not to ignore the presence of these products and to respect the contraindications, even with minute doses.