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Epidemiological typing and prevalence of integrons in multiresistant Acinetobacter strains.

Seventy-seven Acinetobacter isolates were recovered from patients in a Korean hospital during the period from November to December 1998. The isolates were genotyped using randomly amplified polymorphic DNA (RAPD) analysis for epidemiological relationship, and investigated for antibiotic susceptibility and presence of integrons. Sixty-nine Acinetobacter baumannii isolates were distributed into five groups by RAPD profiles, with 5, 1, 60, 2 and 1 in each group. The major RAPD group of 60 isolates was further divided into six subgroups by antibiograms. Eight isolates belonging to Acinetobacter DNA group 13TU were distributed among six RAPD groups. Seventy-three of the Acinetobacter isolates were resistant to eight or more of the antibiotics tested. Integrase genes were detected in 66 of the 69 A. baumannii (96%) and in 5 of the 8 Acinetobacter DNA group 13TU isolates (63%). The intI1 and intI2 genes were found in 63 and 8 isolates, respectively. The intI3 gene was not detected. All integron-carrying isolates were resistant to multiple antibiotics. All strains isolated from more than one patient carried integrons. According to the results, the presence of integrons was significantly (p<0.01) associated with multiple antibiotic resistance and nosocomial spread in Acinetobacter strains.

Acinetobacter↗

Nosocomial transmission of methicillin-resistant Staphylococcus aureus via the surfaces of the dental operatory.

OBJECTIVE: We assess the possibility of methicillin-resistant Staphylococcus aureus (MRSA) transmission via the surfaces of the dental operatory. METHODS: A survey of MRSA contamination on the surfaces of the dental operatory, and an analysis of MRSA transmission via the dental operatory between patients was carried out in the department of special dental care and oral surgery. RESULTS: MRSA was observed on the surfaces of dental operatory including the air-water syringe and reclining chair. Nosocomial infection or colonisation of MRSA occurred in eight out of 140 consecutive patients who had no evidence of MRSA at admission. Antibiograms of 30 antibiotics revealed that the isolates from the eight patients were of the same strain as those from the surface of dental operatory. After treating the patients under a revised infection control (IC) protocol including a single use of barrier covers, MRSA was not detected on the surfaces of the dental operatory, and no nosocomial infection or colonisation occurred during hospitalisation (0/117 patients). CONCLUSIONS: These results suggest that MRSA contaminates the surfaces of the dental operatory, and therefore the dental operatory should be considered a possible reservoir of MRSA.

Cross Infection↗

Isolation and antimicrobial susceptibility pattern of Nocardia among people with culture-proven ocular infections attending a tertiary care eye hospital in Tamilnadu, South India.

AIMS: To evaluate the epidemiology, microbiological features, as well as antibiotic susceptibility patterns of Nocardiafrom cases with ocular nocardial infections seen over a period of 8 years in a tertiary eye care hospital. METHODS: Microbiology records of 164 cases of culture-proven ocular nocardial infection diagnosed between March 1997 and February 2005 were reviewed retrospectively. The outcome data included isolation rate, predisposing factors, demography (age and sex), and category of infection, utility of conventional diagnostic methods, microbiological profile, and antibiogram-resistogram patterns. RESULTS: A total of 164 (3.1%) Nocardiaspecies were identified among 5378 culture-proven cases. Ninety-six (58.5%) isolates were from corneal scrapings followed by vitreous biopsy (17.0%). Most (58.0%) of the cases were between 51 and 80 age groups. Male preponderance was obvious. All the 164 (100%) nocardial infections were identified by culture. Of 125 ocular specimens subjected to Gram's staining, nocaridal filaments were identified in 70 (56%) specimens. In addition to KOH mounting, modified AFB staining was also found to be helpful. Upon in vitrosusceptibility testing, 98.7 and 90.2% of nocardial isolates showed sensitivity towards amikacin and ciprofloxacin, respectively. CONCLUSIONS: Ocular nocardiosis is relatively rare among ocular infections. Amikacin and ciprofloxacin are highly effective in treating ocular nocardiasis. Prompt and accurate microbiological diagnosis and early administration of these antibiotics may have a positive effect on the ocular outcome as well as in controlling nocardial prevalence.

Adolescent↗

Use of pulsed field gel electrophoresis as an epidemiological tool for analysis of sporadic associated strains of Salmonella typhi isolated in Taiwan.

In order to characterize the subtypes of Salmonella typhi which cause sporadic disease in Taiwan, 55 isolates of Salm. typhi obtained from unrelated patients of sporadic cases during 1992-96 were subjected to chromosomal DNA digestion and pulsed field gel electrophoresis (PFGE). When DNAs of these 55 Salm. typhi strains were digested with XbaI, 41 PFGE patterns were observed. Strains sharing the same XbaI digestion pattern could not be further discriminated by PFGE analysis using SpeI and NotI as digestion enzymes. Thus, considerable genetic diversity exists among the Salm. typhi isolates. Although strains of the same patterns were mainly isolated during the same time, recirculation of certain infectious strains could be possible. When 12 antibiotics, i.e. ampicillin, trimethoprim/sulfamethoxazole, erythromycin, norfloxacin, tetracycline, sulphonamide, streptomycin, neomycin, chloramphenicol, kanamycin, cefoperazone and gentamycin were used to test the antibiotic susceptibility for these Salmonella isolates, only three antibiogram patterns were obtained and 49 of the 55 Salm. typhi isolates were found to belong to one pattern. Phage typing and plasmid profiles were also poor in discriminating these strains. Thus, PFGE alone may be used as a powerful tool for analysis of sporadic associated Salm. typhi strains.

Bacterial Typing Techniques↗

Genetic diversity of human isolates of Salmonella enterica serovar Enteritidis in Malaysia.

AIMS: The study was undertaken to determine clonal relationship and genetic diversity of the human strains of Salmonella enterica serovar Enteritidis isolated from 1995 to 2002 from different parts of Malaysia. METHODS AND RESULTS: Antimicrobial susceptibility test, plasmid profiling and pulsed-field gel electrophoresis were applied to analyse 65 human isolates of S. Enteritidis obtained over an eight year period from different parts of Malaysia. Four nonhuman isolates were included for comparison. A total of 14 distinct XbaI-pulsed-field profiles (PFPs) were observed, although a single PFP X1 was predominant and this particular clone was found to be endemic in Malaysia. The incidence of drug resistant S. Enteritidis remained relatively low with only 37% of the strains analysed being resistant to one or more antimicrobial agents. All except one resistant strain carried at least one plasmid ranging in size from 3.7 to 62 MDa giving nine plasmid profiles. The three isolates from raw milk and one from well-water had similar PFPs to that of the human isolates. CONCLUSIONS: Salmonella Enteritidis strains were more diverse than was previously thought. Fourteen subtypes were noted although one predominant clone persisted in Malaysia. The combination of pulsed-field gel electrophoresis, plasmid profiling and antibiograms provided additional discrimination to the highly clonal strains of S. Enteritidis. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report to assess the genotypes of the predominant clinical S. Enteritidis in different parts of the country. As S. Enteritidis is highly endemic in Malaysia, the data generated would be useful for tracing the source during outbreaks of gastroenteritis in the study area.

Anti-Bacterial Agents↗

Shigella and Salmonella strains isolated from children under 5 years in Gaborone, Botswana, and their antibiotic susceptibility patterns.

We isolated Shigella from 43/221 (21%) and Salmonella 8/221 (3%) rectal swabs from children under 5 years with diarrhoea, and found Shigella in two of 100 specimens from children without diarrhoea. Sh. boydii (13%) was the most prevalent Shigella species followed by Sh. flexneri (6%) and Sh. sonnei (2%). The prevalence of various types of Sh. boydii was type 7, 5%; type 9, 3%; type 12 and 16, 2%; and type 18, 1%. Other Shigella serotypes encountered were Sh. flexneri type 6 (4%), type 4 (2%), with Sh. sonnei phase II isolated from 2% of the specimens. The Salmonella species were S. typhimurium and S. paratyphi. The high rate of isolation of Shigella species from children with diarrhoea is indicative of a definite role of this enteropathogen in causing endemic diarrhoea in Gaborone, Botswana. Antibiograms of the predominant isolates showed that most Shigella species were resistant to ampicillin but susceptible to chloramphenicol, and with the exception of Sh. flexneri type 6, also susceptible to gentamicin. The Salmonella species were susceptible to chloramphenicol, collistin-sulphate, gentamicin, cotrimoxazole, and ampicillin.

Anti-Bacterial Agents↗

Prevalence of bacterial faecal pathogens in separated and unseparated stored pig slurry.

AIMS: To examine the prevalence and diversity of bacterial faecal pathogens in unseparated slurry, separated solids and liquid fractions from a commercial pig farm. METHODS: A total of 43 stored slurry specimens originating from a fattening house over the period February-April 2002 were analysed, consisting of unseparated (n = 14) slurry, separated solids (n = 16) and separated liquid (n = 13). Specimens were examined for the presence of five bacterial pathogens including Salmonella spp., Shigella spp., Campylobacter spp., Escherichia coli O157 and Yersinia enterocolitica. Selective enrichment and plating methods were employed for detection of Salmonella spp. and Campylobacter spp. and conventional selective plating techniques for the remaining genera. Antibiogram profiles to 12 antibiotic agents were obtained for all Salmonella isolates obtained. RESULTS: Salmonella spp. were identified in all components of the slurry specimens, whereas Campylobacter spp. was only recovered from the unseparated and separated liquid fractions. In both cases, the separated liquid fraction had the highest prevalence of pathogens and the separated solid fraction had the lowest prevalence. None of the slurry specimens examined were positive for E. coli O157:H7, Shigella spp. or Y. enterocolitica. Twenty-nine isolates of Salmonella were recovered from the slurry specimens, comprising seven serovars, of which Salmonella manhattan was the most prevalent, accounting for over half [15 of 29 (51.7%)] of all Salmonella isolates. Salmonella anatum, Salm. derby, Salm. give, Salm. heidelberg, Salm. simi and Salm. stanley serovars were also recovered. All Salmonella isolates were sensitive to ampicillin, augmentin (amoxicillin/clavulanic acid), chloramphenicol, ciprofloxacin, gentamicin, kanamycin and trimethoprim, but has variable resistance to tetracycline (100%), sulphonamides (84.6%), furazolidone (38.5%), nalidixic acid (15.4%) and streptomycin (15.4%). The majority (57.7%) of isolates displayed antibiotic resistance to at least two antibiotic agents, followed by 34.6% of isolates being resistant to three agents and the remainder (7.7%) being resistant to four antibiotics. SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrated a marked reduction in the prevalence of Campylobacter and Salmonella in the solids component of separated pig slurry. The adoption of control processes such as aeration of slurry prior to its spread onto agricultural land and newer approaches to pathogen reduction should be investigated, to reduce the transmission of pathogens from pig slurry to the environment.

Animal Husbandry↗

Intraoperative contamination of synthetic vascular grafts. Effect of glove change before graft implantation. A prospective randomised study.

OBJECTIVES: to investigate the incidence of intraoperative graft contamination, bacterial species and the influence of change of surgeon's gloves on contamination. DESIGN: a prospective randomised study. MATERIALS AND METHODS: forty patients had implantation of synthetic vascular grafts. All patients received intraoperative cloxacillin (2.0 g) or clindamycin (0.6 g) intravenously. The procedures were randomised to two groups: Group 1 - surgeons changed the gloves before the first contact with the vascular prosthesis and Group 2 - operation without glove change. The growth of all bacterial species from graft segments and from the gloves was recorded. The susceptibility to antibiotics was tested. RESULTS: the number of contaminated grafts was similar in the two groups. Growth of bacteria was recorded from 92.5% (37/40) of the graft segments and 33% (51/156) of glove imprints. Of the cultured species, 75% and 47%, respectively, were identified as coagulase-negative staphylococci (CNS). Twenty-eight per cent of CNS were resistant to cloxacillin, 15% to clindamycin, and 10% to cloxacillin and clindamycin. In all, 25% of the CNS strains were resistant to the prophylactic antibiotic used. In 50% of cases, the antibiogram of the CNS strain recovered from gloves agreed with that of the strain harvested from the graft. CONCLUSIONS: a high incidence of graft contamination was found which was not reduced by changing gloves. However, changing gloves did seem to reduce the number of bacterial species.

Aged↗

Comparative antimicrobial resistance and genomic diversity of Escherichia coli isolated from urinary tract infections in the community and in hospitals.

Well-defined community- and nosocomially-acquired isolates of Escherichia coli responsible for urinary tract infections were studied for their resistance to beta-lactams, quinolones, and co-trimoxazole, antibiotics widely used for treatment of urinary infections. For each strain, an antibiogram was obtained using the Vitek automat, which estimates the minimal inhibitory concentrations of various drugs. Nosocomial strains were significantly more amoxycillin-resistant than community strains (P = 0.01) and were also significantly more resistant to co-trimoxazole (P = 0.025) and first generation quinolones (P = 0.02) than the latter. To determine whether this was due to transmission of strains within the hospital, DNA restriction patterns, established using XbaI enzyme and separation by pulsed-field gel electrophoresis, were compared. Extreme genomic diversity was found among both the community and nosocomial strains. The increased frequency of resistance among nosocomial strains is thus not due to transmission of resistant hospital strains but probably results from the selection of resistant strains from the endogenous flora of patients.

Anti-Bacterial Agents↗

Hospital outbreak of Salmonella virchow possibly associated with a food handler.

A foodborne outbreak of salmonella infection at a private hospital in London in 1994 was found to be associated with eating turkey sandwiches prepared by a food handler. One patient, nine staff, and a foodhandler's baby were confirmed to have Salmonella enterica serotype virchow, phage type 26 infection. The attack rate was estimated to be 5% among the approximately 200 patients and staff at risk. A food handler reportedly became ill days after, but her baby days before, the first hospital case. Although it appeared to be a single outbreak, antibiogram analysis, supplemented by plasmid profile typing, demonstrated that there were two strains of S. virchow involved, one with resistance to sulphonamides and trimethoprim and a second sensitive to these antimicrobial drugs. Mother and child had different strains. The investigation demonstrated the importance of full phenotypic characterization of putative outbreak strains including antimicrobial susceptibility testing. Outbreaks of foodborne infection in hospitals are preventable and are associated with high attack rates and disruption of services. There is a need for good infection control policies and training of all staff involved in patient care as well as in catering services. Consultants in Communicable Disease (CCDCs) should include private hospitals in their outbreak control plans. Good working relations between Infection Control Doctors (ICDs) in the private health sector and their local CCDCs are important if outbreaks are to be properly investigated.

Adult↗

Evidence that hospital hygiene is important in the control of methicillin-resistant Staphylococcus aureus.

Observational and microbiological data were collected from the patients and environment of a male general surgical ward over a period of 27 months from January 1998. Isolates of methicillin-resistant Staphylococcus aureus (MRSA) from patients and environment were typed by antibiogram, bacteriophage and pulsed field gel electrophoresis of chromosomal DNA. In September 1999, an intervention was put in place which included increasing the domestic cleaning time by 57 hours per week, with emphasis on removal of dust by vacuum cleaning, and allocation of responsibility for the routine cleaning of shared medical equipment. From January 1998 to September 1999, despite standard infection control measures (emphasis on hand hygiene, isolation of affected patients and staggered closure and cleaning of ward bays), 69 patients acquired a strain of E-MRSA16. This strain was also widespread in the ward environment. Typing confirmed that isolates from patients and environment were indistinguishable from one another and that the outbreak was due to a single strain. This strain was responsible for postoperative infection in approximately one third of the patients who acquired it. In the six months following the intervention, only three patients were colonized with the outbreak MRSA and monthly surveys failed to detect this strain in the environment. Thorough and continuous attention to ward hygiene and removal of dust was needed, to terminate a prolonged outbreak of MRSA infection on a general surgical ward, in addition to standard infection control measures. Control of hospital-acquired infection with MRSA requires a combination of measures, none of which are completely effective in isolation.

Cost-Benefit Analysis↗

Molecular epidemiology of coagulase-negative staphylococcal bacteraemia in a newborn intensive care unit.

We isolated 55 coagulase-negative staphylococci (CoNS) over two separate 12-month periods (26 in 1993 and 29 in 1996) from the blood of neonates in a neonatal intensive case unit (NICU) in Melbourne, Australia and compared them by pulse-field gel electrophoresis profile (PFGE), random amplification of polymorphic DNA (RAPD) and antibiogram. The most common species were Staphylococcus epidermidis, S. haemolyticus and S. warneri. The majority of such isolates were resistant to penicillin and to either or both of methicillin and gentamicin. During 1993, there was an increase in the number of CoNS bloodstream infections compared with previous years. S. epidermidis was the most common isolate, with 88% assessed as clinically relevant. Using the three typing systems, we identified one likely epidemic clone of S. epidermidis, the isolates of which were resistant to penicillin, gentamicin and erythromycin and possessed the mecA gene. There was complete correlation between the detection of mecA and the phenotypic expression of resistance when zone diameters in the disc diffusion assay were interpreted according to the latest NCCLS guidelines (1999). Profiles of the remaining 1993 isolates were generally heterogeneous, suggesting independent acquisition with some evidence of cross-infection. The predominant bloodstream isolates in 1996 were heterogeneous multi-resistant strains of S. epidermidis, S. haemolyticus and S. warneri, about half of which were assessed as clinically relevant. These data support the view that CoNS are significant nosocomial pathogens in NICU and that resistant clones may be transmitted between babies. Molecular epidemiological tools are helpful for understanding transmission patterns and sources of infection, and are useful for measuring outcomes of intervention strategies implemented to reduce nosocomial CoNS sepsis. PFGE was found to be more discriminatory than RAPD, but the latter provides results in a more timely manner.

Australia↗

Molecular epidemiology of nosocomial infection associated with multi-resistant Acinetobacter baumannii by infrequent-restriction-site PCR.

Acinetobacter baumannii was considered endemic in a university-affiliated tertiary hospital. A significant increase was noted in the proportion of nosocomial infections associated with this micro-organism from 1996 to 1999, although no apparent clusters could be found. Between July 1998 and February 2000, 58 nosocomial isolates of A. baumannii were collected and characterized by antibiotyping and a genotyping method, infrequent-restriction-site PCR (IRS-PCR). High resistance to the 14 antimicrobial agents examined was observed among the isolates. Of the 13 antibiograms detected, eight were multi-resistant to gentamicin and almost all of the traditional and extended-spectrum beta-lactams. These multi-resistant strains consisted of 41 isolates (71%), distributed amongst different wards and intensive care units (ICUs). By IRS-PCR, 23 types were obtained, with one major type found among 28 (48%) isolates. All of these 28 isolates were collected from surgical ICUs. It appears that a single strain of multi-resistant A. baumannii was responsible for the prevalence of nosocomial infection amongst surgical patients, clearly differentiating this outbreak from the previous endemic situation. An efficient molecular typing method played a vital role in making this discrimination.

Acinetobacter↗

Environmental contamination during a carbapenem-resistant Acinetobacter baumannii outbreak in an intensive care unit.

During a three-month period in 1999, 25 strains of carbapenem resistant Acinetobacter baumannii were isolated from 12 of 170 hospitalized intensive care unit (ICU) patients, of which 16 were considered to be clinically significant. These strains were indistinguishable by biotyping and antibiograms, but genotyping was not performed. Appropriate antibiotic treatment, isolation precautions, and infection control education of the staff failed to halt the outbreak. Environmental contamination was therefore investigated, and A. baumannii was found out in 22 (39.3%) of 56 environmental samples obtained by swabbing. Different antibiotic sensitivity patterns were obtained in the majority of these isolates, but four (7.1%) of the strains were found to have the same sensitivity pattern as the strain causing the outbreak. As a result the ICU was closed, equipment and the environment cleaned, with hypochlorite and terminal disinfection carried out. No bacteria were grown on repeat environmental cultures. Environmental contamination has an important reservoir role in outbreaks of A. baumannii in ICUs and must be eradicated in order to overcome such outbreaks.

Acinetobacter Infections↗

Nosocomial outbreak of diarrhoea by enterotoxigenic Escherichia coli among preterm neonates in a tertiary care hospital in India: pitfalls in healthcare.

An outbreak of watery diarrhoea accompanied by low-grade fever and weight loss in 16 preterm neonates (age range 2-20 days) admitted to a neonatal intensive care unit (NICU) over four days in August 2000 is reported. Escherichia coli having similar antibiograms were identified on routine bacterial stool cultures in 14 (87.5%) neonates and none of the other known enteropathogens were detected. An investigation was undertaken to trace the source of infection. Surveillance cultures of swabs from the utensils used to prepare milk feed, culture of the formula feed and all items handled by one particular cook yielded growth of E. coli as did culture of his hand swabs and faecal sample. The causative agent was identified as enterotoxigenic E. coli (ETEC) as toxin production could be demonstrated by reverse passive latex agglutination in all the strains of E. coli isolated both from the infected neonates and the source of infection. The outbreak was effectively controlled by appropriate therapy and institution of proper measures of hygiene after identification of the source of infection.

Animals↗

In vitro antimycotic activity and nail permeation models of a piroctone olamine (octopirox) containing transungual water soluble technology.

Several in vitro studies with a new medical device (Myfungar) containing 0.5% of piroctone olamine (CAS 68890-66-4, octopirox) in a hydroxypropyl chitosan hydroalcoholic solution were performed. The chemical name of the active ingredient is 1-hydroxy-4-methyl-6 (2,4,4-trimethylpentyl)-2(1H)-pyridone; combination with 2-amino-ethanol (1:1). The antimycotic activity was determined in the most common fungi responsible of nail infections such as Candida parapsilosis, Scopulariopsis brevicaulis or Trichophyton rubrum. The minimum inhibitory concentration (MIC), found by means of the broth dilution susceptibility method, ranged between 0.0003% and 0.006% for all pathogens considered. The in vitro permeation study was performed by using bovine hoof membranes inserted in a modified Gummer vertical permeation cell. The experiment showed, at 30 h, a retention of the product in the nail membranes by 11.1% of the applied dose. No piroctone permeation through bovine hoof membranes could be detected by HPLC due to the limit of quantitation of this method. On the other hand, permeation of nail membranes has been demonstrated by a biological assay: the study of in vitro permeation through bovine hoof membranes, performed by biological assay, showed dose-dependent inhibition rings of T. rubrum growth by the tested device, placed either on disks for antibiogram or on nail fragments. The placebo did not show any inhibition. In vitro experimental infection by T. rubrum showed a preventive activity of the tested device on fungal growth as well as a curative activity, as the pathogen was eradicated by the tested solution in previously infected nails.

Animals↗

Lemierre's syndrome: the forgotten disease. An unusual presentation of sepsis.

A 19-year-old girl presented with a septical condition with fever of 40 degrees C, swelling of the right sternocleidomastoid region and abdominal pain. Except for a sore throat with pain strictly localized to the right side of her neck and fever over the last week there were no other clues in her past medical history. An abdominal ultrasound and MRT scan as well as a chest X-ray only showed non-specific findings. The diagnosis of Lemierre's syndrome was established by ultrasonographical detection of right jugular venous thrombosis and perivascular inflammation together with blood cultures positive for Fusobacteria. The patient recovered within days after treatment was initiated with metronidazol according to the antibiogram. Lemierre's syndrome is a life-threatening disease especially in an age group which is less frequently affected by septicaemia. A history of sore throat, Fusobacterium positive blood cultures and ultrasonographical detection of jugular venous thrombophlebitis together with the knowledge of the "forgotten disease" will lead the way to the diagnosis.

Adult↗

[Effect of immunoglobulins on the course of therapy-resistant Klebsiella meningitis].

The case of a 28-year-old patient with refractory Klebsiella meningitis after surgical removal of an angioblastoma in the left cerebellar hemisphere (Lindau's tumour) as described in this article, shows the significance of immunoglobulin therapy in view of the synergistic efficacy increase of antibiotics and immunoglobulin. There were 4 meningitis relapses in a period of 8 months, each time 4 days after discontinuation of antibiotics, the therapy consisting of antibiotics only (penicillin G, gentamycin, lamoxactam, cefotaxim and chloramphenicol). These antibiotics, which were applied in accordance with the antibiogram, were discontinued each 16-32 days after the patient had become afebrile and CSF was free from bacteria. In spite of this, further meningitis relapses followed even when the CSF cell count dropped from 12000/3 to 32/3 cells. An attempt to apply gentamycin suboccipitally failed, since diplopia, nystagmus and headache occurred after a single application. The combination of chloramphenicol orally and immunoglobulin intravenously resulted for the first time in complete freedom from bacteria in the CSF. A single intrathecal application of 1 g immunoglobulin caused a temporary increase in CSF cells to 1200/3 and an anal temperature increase from 37% to 38% C. Urticaria exanthema was observed twice as a side effect of immunoglobulin therapy.

Anti-Bacterial Agents↗