Volume 10, Issue 2, 2002
Review
Present and future of cephalosporins
Cornaglia Giuseppe
The cephalosporins today, and particularly the third-generation cephalosporins, still possess an activity spectrum and microbiological potency such that several authors continue to regard them as the gold standard of beta-lactam antibiotic therapy. Comparison with the rapid onset of resistance to other extensively used drugs, such as the macrolides and quinolones, places the emphasis once again squarely on the great reliability of the antibacterial action of the cephalosporins and, particularly, on the validity of their targets at the bacterial cell level.
The beneficial use of cephalosporins for a vast range of infectious diseases is amply confirmed by the most authoritative international guidelines and bears witness to the role of great importance that these drugs still play in all fields of antibiotic therapy, as a result of the variety of the compounds available, their broad spectrum of antibacterial activity, their multiple clinical potentialities and their excellent tolerability.
The cephalosporins therefore continue to constitute a firm reference point in the overcrowded antibiotics scene and, if used appropriately, promise to conserve their leading role for a long time to come.
Original article
Methicillin-resistant Staphylococcus aureus: a three-year epidemiological and microbiological survey of high-risk patients
Manfredi Roberto,
Nanetti Anna,
Valentini Roberta,
Calza Leonardo,
Chiodo Francesco
In order to assess the frequency, and epidemiological and microbiological features, of respiratory and blood stream infection due to methicillin-resistant Staphylococcus aureus in high-risk patients, all S. aureus strains cultured from reliable clinical specimens (respiratory secretions obtained by tracheo-bronchial aspirate or bronchoalveolar lavage, or blood cultures), were prospectively evaluated over a three-year period, in six inpatient wards selected on the ground of an elevated frequency of severe and/or nosocomially-acquired infections, because of the prevalence of immunocompromised patients, organ transplant recipients, or need of intensive care. Repeatedly positive cultures obtained from a single patient within 30 days were considered as one isolate. Of 507 S. aureus strains responsible for pneumonia or sepsis in the selected wards, 317 (62.5%) proved methicillin-resistant, in absence of significant variations throughout the study period, and according to the specimen origin. Methicillin-resistant S. aureus strains prevailed over sensitive ones in all examined wards (from a 95% rate of the respiratory intensive care unit, to 55.9% of the pneumology department), save the neonatal and pediatric intensive care unit (41.4%). Most of methicillin-resistant S. aureus isolates were recovered from lower airways, compared with blood cultures (p<.0001). The majority of the 317 methicillin-resistant strains were found in the general intensive care unit (42.6%), followed by the pneumology department (18%), and the respiratory intensive care unit (16.4%). Among methicillin-resistant S. aureus strains, a broad variation of sensitivity to other antimicrobial agents was observed: from 3.3% of erythromycin, to 76.9% of chloramphenicol, and 79.7% of cotrimoxazole; glycopeptide antibiotics remained effective against all cultured strains. In our three-year survey of more than 500 episodes of documented staphylococcal infection involving high-risk patients, methicillin resistance was a very common feature, observed at a greater frequency than that reported in literature studies focusing on surgical, pneumological, or intensive care settings. A long-term microbiological monitoring of high-risk inpatient wards may allow a continued update of local antimicrobial susceptibility maps, and significantly add to both chemoprophylaxis and empiric treatment strategies of patients which are either immunocompromised or hospitalized for a long period.
Enteric infections in Perugia’s area: laboratory diagnosis, clinical aspects and epidemiology during 2001
Crotti Daniele,
D'Annibale Maria Letizia,
Fonzo Giovanna,
Medori Maria Chiara,
Ubaldi Manuela
During 2001 we analyzed 523 stool specimens (330 children, 193 adults) of patients with recent diarrhoea. We processed all specimens for protozoa, rotavirus, adenovirus, toxin A of C. difficile, and usual enteropathogen bacteria. Salmonella prevailed in 12.8% of cases (16.4% among children, 6.7% among adults), Campylobacter in 9.9% (11.5% and 7.3%), C. difficile toxin A producer in 11.3% (13.7% and 8.1%); other bacteria generally prevailed in 2.4%, protozoa in 2.7%. Among children rotavirus prevailed in 41.4%, adenovirus in 3.6%. Enteritis prevailed in children between 1 and 6 years of age. All pathogens were reported during all the seasons, but salmonellosis and campylobacteriosis were more frequent during spring and summer, rotavirus infections during the winter. Non particular and/or specific correlations could be observed between clinical manifestations and pathogen agents; anyway only bacteria were identified among invasive enterites. Vomitus was more frequent in rotavirus infections. Finally the Authors suggest a rational and efficacious methodology for diagnosis of presumptive infectious diarrhoeas.
Antibiotic prophylaxys in pediatric surgery of genito-urinary abnormalities
Campobasso Paolo
Ninety-two patients in the age range of 2,5 and 16 years with hypospadias (28 cases), vescicorenal reflux (22 cases), hydronephrosis (16 cases) and a series of other congenital genitourinary abnormalities underwent one or more surgical interventions performed by an unique surgeon at the department of Pediatric Surgery, S. Bortolo Hospital, Vicenza. The more frequently performed interventions were the plastic of the urethra (28 pts, 30,4%), that of the pyeloureteral joint (15 pts, 16,3%) and the modelling and the reimplantation of the ureter/ureters (12 pts, 13%).
The interventions were considered as clean-contaminated, because all patients had a temporary urinary derivation with vescical catheters, uretral or pyelovescical stents. An antimicrobial prophylaxis was undertaken in all cases in order to prevent postoperatory infections.
Ceftriaxone at a mean dosage of 50 mg/kg was administered to all patient for a mean duration of 5,5 days, in 79 cases by the intravenous and in 13 cases by the intramuscolar route. Three patients received also metronidazol because of a concomitant intestinal surgery. The objective of this retrospective trial is to evaluate the efficacy of an antibiotic prophylaxis in pediatric genitourinary surgery with temporary urinary drainage. Data analysis evidenced a very low incidence of postoperatory infections, that occurred only in 2 patient on 92. It can be therefore concluded that ceftriaxone is effective and well tolerated when administered for the prevention of postoperative infections in urological interventions.
Microbiological surveillance in an intensive care unit of a large roman hospital
Franchi Cristiana,
Venditti Mario,
Rocco Monica,
Spadetta Gustavo,
Vullo Vincenzo,
Raponi Massimiliano,
Orsi Giovanni Battista
Infection surveillance in ICU is foundamental to monitor endemic rates, to identify outbreaks on-time in order to activate control procedures implementing a correct empirical antibiotic treatment. The data collection surveillance software CIN-20002 was established in the Teaching Hospital Umberto I ICU to monitor the following site-specific infection rates: urinary tract infections (UTI), pneumonia (PNE), blood stream infections (BSI), surgical site infections (SSI). According to CDC definitions all patients developing infection 48 hours or more after ward admission were included. Furthermore risk factors (i.e. age, sex, SAPS II), invasive procedures (i.e. endotracheal intubation, vascular and urinary catheterisation), microbiological isolates and their antibiotic susceptibility were screened. Overall 279 patients (183 men and 96 women) were admitted; age 54,8 ± 20,3 years (mean), SAPS II 44,4 ± 17,1 (mean) and average ward stay 13,3 ± 17,8 days. Results showed a total of 121 infection episodes (56 PNE , 51 BSI, 10 UTI e 4 SSI) in 80 patients (28,7%). Standardized infection rates associated to invasive procedures were: Urinary catheter-associated UTI rate (2.9/1000), Ventilator-associated PNE rate (20.4/1000), Vascular catheter-associated BSI rate (19.1/1000). Among the infected patients the most common microrganisms isolated were P. aeruginosa (31,8%), MRSA (14,8%), A. baumanni (12,5%) e S. maltophilia (8,5%). Considering site-specific infections: PNE (P. aeruginosa 38,3% and MRSA 18,1%), BSI (MR CNS 21,9% and P. aeruginosa 17,2%), UTI (P. aeruginosa 70,0%). The surveillance software CIN-2000 proved to be very accurate, usefull and easy to use. The results showed a high incidence of infections associated to invasive procedures and the presence of multiresistant bacteria.
Comparative in vitro Bacteriostatic and Bactericidal Activity of Levofloxacin and Ciprofloxacin against Urinary Tract Pathogens Determined by MIC, MBC, Time-Kill Curves and Bactericidal Index Analysis
Noviello Silvana,
Ianniello Filomena,
Leone Sebastiano,
Esposito Silvano
The Bactericidal Index is a new way to assess bactericidal activity, representing the total bacterial kill over a drug concentration range. The aim of the study was to compare the in vitro activity of LEV with that of CIP against uropathogens determined by MIC, MBC, time-kill curves and BI analysis.
A total of 141 strains [E. coli (EC) n=30; Klebsiella spp n=30; P aeruginosa (PA) n=35; P. mirabilis (PM) n=21; E. cloacae n=25] were preliminarily tested for MIC evaluation. MICs were obtained by 100µl microbroth dilution, followed by whole volume transfer for MBC determination. The time-kill tests were determined with 3 isolates each of EC, PA and PM and the killing monitored over 24h. FQs were added to a final concentration of 0.25, 0.5, 1, 2, 4, 8 and 16xMIC. Aliquots were sub-cultured at intervals. To assess the BI, overnight bacterial cultures were diluted to about 107 CFU/ml and set up containing a range of drug concentrations.
MIC values of LEV were slightly higher than CIP; MBC/MIC ratio was in the range 1:1/1:2. LEV showed 99.9% killing after 6h against EC and after 3 h against PA at 1xMIC and after 3h at 2xMIC against PM in contrast with CIP (after 3h at 8xMIC). The BI data showed that FQs became more bactericidal with increasing incubation time and evidenced the enhanced bactericidal potency of LEV. A paradoxical effect was observed for all PA and PM strains, with slower killing at high concentrations of LEV (128µg/ml) at 24h and CIP (4µg/ml) at 3h.
CIP was more active in terms of MIC values but LEV exhibited similar or even better bactericidal activity when time-kill curves or BI were compared. Calculation of BI allows the bactericidal activity of drugs, at clinically relevant concentrations, to be readily compared.
Effects induced by the introduction of highly active antiretroviral therapy (HAART) on disseminated bacterial infection during HIV disease
Manfredi Roberto,
Chiodo Francesco
In order to assess the frequency, risk factors, etiology, and clinical outcome of HIV-related sepsis and bacteremia, according to the introduction of highly active antiretroviral therapy (HAART), all episodes occurred in patients hospitalized during years 1993-1995 (pre-HAART era), have been compared with those diagnosed after HAART introduction (years 1997-2000). On the whole, 498 patients suffered from sepsis/bacteremia in the two considered time periods, but the frequency of this complication proved significantly lower during the last 4 years, as opposed to the pre-HAART period (5.3 versus 18.2 episodes per patient-year: p<.0001). Among potential risk factors, during the last 4 years a significant rise of mean CD4+ lymphocyte count was observed (p<.0001), together with a reduced frequency of neutropenia (absolute neutrophil count <1000 cells/µL) (p<.02), and a less frequent association with an advanced HIV disease (stage C, CDC) (p<.03). Despite a remarkably reduced mean duration of admission, during the HAART era a significant increase of nosocomial- versus community-acquired infection occurred (p<.002), with a related greater frequency of gram-negative bacilli of environmental origin: Pseudomonas, Xanthomonas (Stenotrophomonas), Acinetonbacter spp., and non-fermenting bacilli (p<.05). No significant difference was noticed between the two considered periods, as to patients’ age, gender, and type of exposure to HIV, use of central vascular lines, prior administration of steroids, antimicrobials, and cotrimoxazole, as well as disease outcome (including the frequency of related deaths). On the whole, the significant drop of frequency of HIV-associated sepsis/bacteremia occurred after the introduction of HAART (over 3.4-fold, compared with that observed prior to HAART use), proved associated with a reduced degree of immunodeficiency, and a less advanced underlying disease. The proportional increase of nosocomial infections and related pathogens did not match with the apparently significant reduction of mean admission time. A careful and continued monitoring of epidemiological, microbiological, clinical, and treatment features of disseminated bacterial disease looks mandatory even during the HAART era, in order to update therapeutic and prophylactic strategies of HIV disease management.
Case report
Myocardial infarction in hiv patients treated with protease inhibitors: report of two cases
Sabbatani Sergio,
Dentale Nicola
The Authors describe two cases of HIV patients treated with Protease Inhibitors that have gone on to suffer from lipodistrofy, metabolic disorder, diabete and myocardial infarction (fatal in one of them). The surviving patient underwent a Percutaneous Transluminal Coronary Angioplasty (PTCA) with improvement of the acute coronary symdrome. In the light of the review of literature and our observations, we propose some considerations about prevention, diagnostic and terapeutic management of HIV patients treated with IP and cardiovascular risk.
