The Treatment of Possible Severe Infection in Infants: An Open Randomized Safety Trial of Parenteral Benzylpenicillin and Gentamicin Versus Ceftriaxone in Infants <60 days of Age in Malawi

BACKGROUND: The World Health Organization recommends benzylpenicillin and gentamicin as antimicrobial treatment of infants with sepsis in low income settings (LICs), and ceftriaxone or cefotaxime as an alternative. In a meta-analysis from 13 LICs, Staphylococcus aureus, Klebsiella spp. and E.coli accounted for 55% of infants with sepsis. In a review of bacterial meningitis, resistance to third generation cephalosporins was > 50% of all isolates, and 44% of Gram-negative isolates were gentamicin resistant. However, ceftriaxone may cause neonatal jaundice and gentamicin may cause deafness. Therefore, we compared parenteral benzylpenicillin plus gentamicin to ceftriaxone as first line treatment, assessing outcome and adverse events. METHODS:: This was an open randomized trial carried out in the Queen Elizabeth Central Hospital, Blantyre, Malawi from 2010 to 2013. Infants < 60 days of age with possible severe sepsis received either benzylpenicillin and gentamicin or ceftriaxone. Adverse events and outcomes were recorded until 6 months post discharge. RESULTS:: 348 infants were included in analyses. Outcome in the benzylpenicillin and gentamicin or ceftriaxone groups was similar; deaths were 13.7% and 16.5% and sequelae 14.5% and 11.2% respectively. More infants in the penicillin/gentamicin group required phototherapy: 15% v 5%, p=0.03. Thirteen (6%) survivors had bilateral hearing loss. There was no difference between the treatment groups. By 6 months post discharge 11 more infants had died and 17 more children were found to have sequelae. CONCLUSIONS:: Ceftriaxone and gentamicin are safe for infants in our setting. Infants should receive long term follow up as many poor outcomes occurred after hospital discharge

Investigation of Staphylococcus strains with heterogeneous resistance to glycopeptides in a Turkish university hospital

BACKGROUND: The hetero-glycopeptide intermediate staphylococci is considered to be the precursor of glycopeptide intermediate staphylococci especially vancomycin intermediate Staphylococcus aureus (VISA). For this purpose, we aimed to investigate the heterogeneous resistance to glycopeptide and their frequencies in 135 Staphylococcus strains. METHODS: Heterogeneous resistance of Staphylococcus strains was detected by inoculating the strains onto Brain Heart Infusion agar supplemented with 4 mg/L of vancomycin (BHA-V4). Agar dilution method was used for determining MICs of glycopeptides and population analysis profile was performed for detecting frequency of heterogeneous resistance for the parents of selected strains on BHA-4. RESULTS: Eight (6%) out of 135 Staphylococcus strains were exhibited heterogeneous resistance to at least one glycopeptide. One (1.2%) out of 81 S. aureus was found intermediate resistance to teicoplanin (MIC 16 mg/L). Other seven strains were Staphylococcus haemolyticus (13%) out of 54 coagulase negative staphylococci (CoNS). Six of the seven strains were detected heterogeneously reducing susceptibility to vancomycin (MICs ranged between 5–8 mg/L) and teicoplanin (MICs ranged between 32–64 mg/L), and one S. haemolyticus was found heterogeneous resistance to teicoplanin (MIC 32 mg/L). Frequencies of heterogeneous resistance were measured being one in 10(6 )– 10(7 )cfu/ml. MICs of vancomycin and teicoplanin for hetero-staphylococci were determined as 2–6 folds and 3–16 folds higher than their parents, respectively. These strains were isolated from six patients (7%) and two (4%) of health care wokers hands. Hetero-VISA strain was not detected. CONCLUSION: Heterogeneous resistance to glycopeptide in CoNS strains was observed to be significantly more emergent than those of S. aureus strains (vancomycin P 0.001, teicoplanin, P 0.007). The increase MICs of glycopeptide resistance for subpopulations of staphylococci comparing with their parents could be an important clue for recognizing the early steps in the appearance of VISA strains. We suggested to screen clinical S. aureus and CoNS strains, systematically, for the presence of heterogeneously resistance to glycopeptide

Characterization of coagulase-negative staphylococcal isolates from blood with reduced susceptibility to glycopeptides and therapeutic options

<p>Abstract</p> <p>Background</p> <p>Coagulase-negative staphylococci (CoNS) are a major cause of nosocomial blood stream infection, especially in critically ill and haematology patients. CoNS are usually multidrug-resistant and glycopeptide antibiotics have been to date considered the drugs of choice for treatment. The aim of this study was to characterize CoNS with reduced susceptibility to glycopeptides causing blood stream infection (BSI) in critically ill and haematology patients at the University Hospital Tor Vergata, Rome, Italy, in 2007.</p> <p>Methods</p> <p>Hospital microbiology records for transplant haematology and ICU were reviewed to identify CoNS with elevated MICs for glycopeptides, and isolates were matched to clinical records to determine whether the isolates caused a BSI. The isolates were tested for susceptibility to new drugs daptomicin and tigecycline and the genetic relationship was assessed using f-AFLP.</p> <p>Results</p> <p>Of a total of 17,418 blood cultures, 1,609 were positive for CoNS and of these, 87 (5.4%) displayed reduced susceptibility to glycopeptides. Clinical review revealed that in 13 cases (7 in haematology and 6 in ICU), CoNS with reduced susceptibility to glycopeptides were responsible for a BSI. <it>Staphylococcus epidermidis </it>was the causative organism in 11 instances and <it>Staphylococcus haemolyticus </it>in 2. The incidence of oxacillin resistance was high (77%), although all isolates remained susceptible to linezolid, daptomycin and tigecycline. Fingerprinting of CoNS identified one clonal relationship between two isolates.</p> <p>Conclusion</p> <p>Multi-resistant CoNS with reduced susceptibility to glycopeptides, although still relatively infrequent in our hospital, are emerging pathogens of clinical concern. Surveillance by antibiotyping with attention to multi-resistant profile, and warning to clinicians, is necessary.</p