Core outcome set for perinatal interventions for congenital diaphragmatic hernia.

OBJECTIVE: To develop a core set of prenatal and neonatal outcomes for clinical studies evaluating perinatal interventions for congenital diaphragmatic hernia, using a validated consensus-building method. METHODS: An international steering group comprising 13 leading maternal-fetal medicine specialists, neonatologists, pediatric surgeons, patient representatives, researchers and methodologists guided the development of this core outcome set. Potential outcomes were collected through a systematic review of the literature and entered into a two-round online Delphi survey. A call was made for stakeholders with experience of congenital diaphragmatic hernia to review the list and score outcomes based on their perceived relevance. Outcomes that fulfilled the consensus criteria defined a priori were discussed subsequently in online breakout meetings. Results were reviewed in a consensus meeting, during which the core outcome set was defined. Finally, the definitions, measurement methods and aspirational outcomes were defined in online and in-person definition meetings by a selection of 45 stakeholders. RESULTS: Overall, 221 stakeholders participated in the Delphi survey and 198 completed both rounds. Fifty outcomes met the consensus criteria and were discussed and rescored by 78 stakeholders in the breakout meetings. During the consensus meeting, 93 stakeholders agreed eventually on eight outcomes, which constituted the core outcome set. Maternal and obstetric outcomes included maternal morbidity related to the intervention and gestational age at delivery. Fetal outcomes included intrauterine demise, interval between intervention and delivery and change in lung size in utero around the time of the intervention. Neonatal outcomes included neonatal mortality, pulmonary hypertension and use of extracorporeal membrane oxygenation. Definitions and measurement methods were formulated by 45 stakeholders, who also added three aspirational outcomes: duration of invasive ventilation, duration of oxygen supplementation and use of pulmonary vasodilators at discharge. CONCLUSIONS: We developed with relevant stakeholders a core outcome set for studies evaluating perinatal interventions in congenital diaphragmatic hernia. Its implementation should facilitate the comparison and combination of trial results, enabling future research to better guide clinical practice. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Fetal endoscopic tracheal occlusion reduces pulmonary hypertension in severe congenital diaphragmatic hernia.

OBJECTIVE: Fetal endoscopic tracheal occlusion (FETO) is associated with increased perinatal survival and reduced need for extracorporeal membrane oxygenation (ECMO) in fetuses with severe congenital diaphragmatic hernia (CDH). This study evaluates the impact of FETO on the resolution of pulmonary hypertension (PH) in fetuses with isolated CDH. METHODS: We reviewed retrospectively the medical records of all fetuses evaluated for CDH between January 2004 and July 2017 at a single institution. Fetuses with additional major structural or chromosomal abnormalities were excluded. CDH cases were classified retrospectively into mild, moderate and severe groups based on prenatal magnetic resonance imaging indices (observed-to-expected total fetal lung volume and percentage of intrathoracic liver herniation). Presence of PH was determined based on postnatal echocardiograms. Logistic regression analyses were performed to evaluate the relationship between FETO and resolution of PH by 1 year of age while controlling for side of the CDH, use of ECMO, gestational age at diagnosis, gestational age at delivery, fetal gender, sildenafil use at discharge and CDH severity. Resolution of PH by 1 year of age was compared between a cohort of fetuses with severe CDH that underwent FETO and a cohort that did not have the procedure (non-FETO). A subanalysis was performed restricting the analysis to isolated left CDH. Parametric and non-parametric tests were used for comparisons. RESULTS: Of 257 CDH cases evaluated, 72% (n = 184) had no major structural or chromosomal anomalies of which 58% (n = 107) met the study inclusion criteria. The FETO cohort consisted of 19 CDH cases and the non-FETO cohort (n = 88) consisted of 31 (35%) mild, 32 (36%) moderate and 25 (28%) severe CDH cases. All infants with severe CDH, regardless of whether they underwent FETO, had evidence of neonatal PH. FETO (OR, 3.57; 95% CI, 1.05-12.10; P = 0.041) and ECMO (OR, 5.01; 95% CI, 2.10-11.96; P < 0.001) were independent predictors of resolution of PH by 1 year of age. A higher proportion of infants with severe CDH that underwent FETO had resolution of PH by 1 year after birth compared with infants with severe CDH in the non-FETO cohort (69% (11/16) vs 28% (7/25); P = 0.017). Similar results were observed when the analysis was restricted to cases with left-sided CDH (PH resolution in 69% (11/16) vs 28% (5/18); P = 0.032). CONCLUSION: In infants with severe CDH, FETO and ECMO are independently associated with increased resolution of PH by 1 year of age. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Titanium-released from dental implant enhances pre-osteoblast adhesion by ROS modulating crucial intracellular pathways.

It is important to understand the cellular and molecular events that occur at the cell-material interface of implants used for bone repair. The mechanisms involved in the initial stages of osteoblast interactions with the surface of the implant material must be decisive for cell fating surrounding them. In order to address this issue, we decided to investigate if conditioned medium for dental implants was able to modulate murine pre-osteoblast metabolism. First, we determined the concentration of titanium (Ti)-containing conditioned medium and found that it was 2-fold increased (p < 0.0001). We have reported that this conditioned medium significantly up-modulated pre-osteoblast adhesion up to 24 h (p < 0.0001). In parallel, our results showed that both phosphorylations of FAK (focal adhesion kinase) at Y397 (p < 0.0011) and Cofilin at Ser03 (p < 0.0053) were also up-modulated, as well as for Rac1 expression (p < 0.0175); both of them are involved with cell adaptation by rearranging cytoskeleton actin filaments. Thereafter, Ti-containing medium stimulated ROS (reactive oxygen species) production by pre-osteoblast cells, and it is very possible that ROS compromised PTP-1B (protein tyrosine phosphatase 1B) activation since PTP1B was down-phosphorylated (p < 0.0148). The low PTP activity guarantees the phosphorylation of FAK at Y-residue, causing better pre-osteoblast adhesion in response to Ti-containing medium. Altogether, these data indicate that ROS indirectly modulate FAK phosphorylation in response to Ti-released from dental implants. Taken the results in account, these data showed for the first time that the implanted dental device is able to dynamically affect surrounding tissues, mainly by promoting a better performance of the pre-osteoblast cells. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2968-2976, 2017.

Mind the gap: can videolaryngoscopy bridge the competency gap in neonatal endotracheal intubation among pediatric trainees? a randomized controlled study.

BACKGROUND: To study the impact of videolaryngoscopy (VL) on intubation success among pediatric trainees compared with direct laryngoscopy (DL). METHODS: One hundred pediatric residents were enrolled in a randomized, crossover, simulation study comparing VL to DL. Following a didactic session on neonatal intubation, residents intubated a standard neonatal mannequin. Three Neonatal Resuscitation Program (NRP) scenarios were then conducted, followed by a mannequin intubation with the alternate device. Number of attempts and time to intubation were recorded for all intubations. RESULTS: Proportion of successful intubations on first attempt was greater with VL compared with DL (88% versus 63%; P=0.008). The DL group increased success after crossover with VL (63% versus 89%; P=0.008). Exposure to VL also reduced intubation time after device crossover (median intubation time: 31 versus 17 s; P=0.048). CONCLUSIONS: VL increased the success of endotracheal intubation by pediatric residents in simulation, with skills transferrable to DL.

Fetal lung volume and quantification of liver herniation by magnetic resonance imaging in isolated congenital diaphragmatic hernia.

OBJECTIVE: To determine associations between fetal lung and liver herniation volumes measured by magnetic resonance imaging (MRI) and mortality/need for extracorporeal membrane oxygenation (ECMO) in cases of isolated congenital diaphragmatic hernia (CDH). A secondary objective was to compare prenatal MRI parameters with two-dimensional ultrasound lung measurements. METHODS: A retrospective review of medical records of all fetuses with isolated CDH evaluated between January 2004 and July 2012 was performed. The following MRI parameters were measured at 20-32 weeks: observed/expected total fetal lung volume (o/e-TLV), predicted pulmonary volume (PPV), percentage of liver herniated into the fetal thorax (%LH) and the liver/thoracic volume ratio (LiTR). These were compared with the ultrasound-determined lung-to-head ratio (LHR) and the observed/expected LHR (o/e-LHR) in the same cohort. The predictive value of MRI and ultrasound parameters for mortality and the need for ECMO was evaluated by univariate, multivariate and factor analysis and by receiver-operating characteristics curves. RESULTS: Eighty fetuses with isolated CDH were evaluated. Overall mortality was 18/80 (22.5%). Two newborns died a few hours after birth. ECMO was performed in 29/78 (37.2%) newborns, with a survival rate of 48.3% (14/29). The side of the diaphragmatic defect was not associated with mortality (P = 0.99) or the need for ECMO (P = 0.48). Good correlation was observed among o/e-TLV, PPV, LHR and o/e-LHR as well as between %LH and LiTR (r = 0.89; P < 0.01); however, fetal lung measurements and measures of liver herniation were not correlated (all P > 0.05). All parameters were statistically associated with mortality or the need for ECMO. The best combination of measurements to predict mortality was o/e-TLV and %LH, with 83% accuracy. CONCLUSION: Mortality and the need for ECMO in neonates with isolated CDH can be best predicted using a combination of MRI o/e-TLV and %LH.

Tight glucose control versus intermediate glucose control: a quasi-experimental study.

Intensive insulin treatment is associated with an increased risk of hypoglycaemia. The purpose of this study was to evaluate two different strategies: tight glucose control (TGC) versus intermediate glucose control (IGC). In this quasi-experimental study, 130 critically ill patients were assigned to receive either the TGC protocol (n=65), according to which blood glucose levels were maintained between 4.4 and 6.1 mmol/l, or the IGC protocol (n=65), according to which blood glucose levels were maintained between 4.4 and 8.0 mmol/l. A total of 52 subjects (40%) were diabetic and 63 (49%) were septic. In the IGC group, glucose levels were stabilised in the target range for a longer period of time when compared to the TGC group (63 vs. 41%, P < 0.001). The median capillary blood glucose level was 6.7 mmol/l in the TGC group (6.2 to 7.2) and 7.9 mmol/l (7.0 to 8.5) in the IGC group (P < 0.001). The incidence of hypoglyacemia less than 2.2 mmol/l was 21.5% in the TGC group and 1.5% in the IGC group (P < 0.001), and the incidence of hypoglycaemia less than 3.3 mmol/l was 67.7 and 26.2% (P < 0.001) in the two groups, respectively. Diabetes (odds ratio 2.88, CI 1.22 to 6.84) and the TGC protocol (odds ratio 7.39, CI 3.15 to 1735) were identified as independent risk factors for hypoglycaemia less than 3.3 mmol/l. Mechanical ventilation (odds ratio 4.33, CI 1.16 to 16.13), medical illness (odds ratio 2.88, CI 1.20 to 6.99) and hypoglycaemia (< 3.3 mmol/l) (odds ratio 299, CI 1.21 to 7.41) were independent factors associated with mortality. TGC is difficult to accomplish in routine intensive care unit settings and is associated with a significant increase in the incidence of hypoglycaemia. Hypoglycaemia < 3.3 mmol/l is an independent risk factor for in-hospital mortality.

Schistosomiasis associated pulmonary hypertension.

Schistosomiasis is one of the most prevalent infectious diseases, endemic in more than 70 countries, mainly within the developing world. More than 200 million people might be infected worldwide; about 20 million of those might develop severe disease. The hepatosplenic form of schistosomiasis is the most prevalent form of chronic disease, characterised by the presence of periportal fibrosis and portal hypertension. Pulmonary hypertension is a well-recognised complication of hepatosplenic schistosomiasis. Recent prevalent studies revealed that schistosomiasis patients may develop precapillary and postcapillary forms of pulmonary hypertension, reinforcing the role of invasive haemodynamic measurements for the proper diagnosis. These studies also demonstrated that schistosomiasis associated pulmonary arterial hypertension may represent the most prevalent form of pulmonary arterial hypertension (PAH). Many aspects regarding the appropriate management of Sch-PAH patients still remain to be elucidated, as the use of specific PAH therapy. Although the ongoing control programmes that started within the 1980s have clearly improved the schistosomiasis cenario worldwide, Sch-PAH will be seen for decades after proper control is reached, strengthening the current need for comprehensive studies aiming to clarify the multiple mechanisms involved in the pathophysiology of this particular subgroup of PAH.

Urinary F2-isoprostanes are poor prognostic indicators for the development of bronchopulmonary dysplasia.

OBJECTIVE: Oxygen toxicity is thought to contribute to the development of bronchopulmonary dysplasia (BPD). Oxidant injury leads to formation of F(2)-isoprostanes (F(2)-IsoP). We hypothesized that urinary excretion of the stable metabolite of F(2)-IsoP, 8-iso-PGF(2alpha), would be higher in infants who develop BPD than those who did not. METHODS: Forty infants <30-weeks gestational age (GA) were enrolled, 24 infants with BPD and 16 without BPD. Urine specimens were collected weekly and stored at -80 degrees C until analyzed. Urinary 8-iso-PGF(2alpha) was measured by gas chromatography/mass spectrometry (GC-MS) and normalized to creatinine excretion. RESULTS: GA and birth weight (BW) were lower in infants who developed BPD than those who did not. Urinary 8-iso-PGF(2alpha) levels in the first or third weeks of age were not significantly different between the two groups. CONCLUSION: Urinary excretion of 8-iso-PGF(2alpha) in early postnatal life in preterm infants is not correlated with the development of BPD.

Effect of sitaxsentan treatment on quality of life in pulmonary arterial hypertension.

In recent years new therapeutic options have been developed for the management of pulmonary arterial hypertension (PAH). Sitaxsentan is an oral, once daily, highly selective endothelin A receptor antagonist that recently demonstrated a positive effect on functional capacity and haemodynamics of PAH patients. The aim of this study is to evaluate the effect of sitaxsentan in the quality of life (QOL) of PAH patients. Twenty-three patients with idiopathic PAH or PAH associated to collagen vascular diseases were evaluated at baseline and after 16 weeks of treatment with sitaxsentan 100 mg orally, once daily. 6-min walk test distance (6MWD) and QOL questionnaire (QOLQ) (SF-36) were obtained at baseline and at week 16. There was a significant improvement in functional capacity evaluated by 6MWD (472 m vs. 490 m, p = 0.03) and also in the physical component of the QOLQ (p < 0.01). Evaluating each of the domains of the SF-36 QOLQ, those more related to physical capacity presented a significant increase while the domains related to the mental component presented a trend of improvement, without reaching statistical significance. Sitaxsentan improves QOL in patients with PAH mainly through the domains related to functional capacity.

Clinical response to sildenafil in pulmonary hypertension associated with Gaucher disease.

There are few reports of pulmonary hypertension in Gaucher disease. We report a patient who showed significant clinical improvement after treatment with sildenafil.

Red blood cell transfusion does not increase oxygen consumption in critically ill septic patients.

BACKGROUND: Red blood cell (RBC) transfusion is commonly used to increase oxygen transport in patients with sepsis. However it does not consistently increase oxygen uptake at either the whole-body level, as calculated by the Fick method, or within individual organs, as assessed by gastric intra-mucosal pH. AIM: This study evaluates the hemodynamic and oxygen utilization effects of hemoglobin infusion on critically ill septic patients. METHODS: Fifteen septic patients undergoing mechanical ventilation whose hemoglobin was <10 g% were eligible. Ten patients (APACHE II: 25.5 +/- 7.6) received an infusion of 1 unit of packed RBC over 1 h while sedated and paralyzed. The remaining five control patients (APACHE II: 24.3 +/- 6.0) received a 5% albumin solution (500 ml) over 1 h. Hemodynamic data, gastric tonometry and calorimetry were obtained prior to and immediately after RBC transfusion or 5% albumin infusion. RESULTS: Transfusion of RBC was associated with an improvement in left ventricular systolic work index (38.6 +/- 12.6 to 41.1 +/- 13.0 g/min/m2; P = 0.04). In the control group there was no significant change in the left ventricular systolic work index (37.2 +/- 14.3 to 42.2 +/- 18.9 g/min/m2). An increase in pulmonary vascular resistance index (203 +/- 58 to 238 +/- 49 dyne/cm5/m2; P = 0.04) was also observed, while no change was produced by colloid infusion (237 +/- 87.8 to 226.4 +/- 57.8 dyne/cm5/m2). Oxygen utilization did not increase either by Fick equation or by indirect calorimetry in either group. Gastric intramucosal pH increased only in the control group but did not reach statistical significance. CONCLUSION: Hemoglobin increase does not improve either global or regional oxygen utilization in anemic septic patients. Furthermore, RBC transfusion may hamper right ventricular ejection by increasing the pulmonary vascular resistance index.

In vitro activities of ertapenem (MK-0826) against recent clinical bacteria collected in Europe and Australia.

Ertapenem (MK-0826, L-749,345) is a 1-beta-methyl carbapenem with a long serum half-life. Its in vitro activity was determined by broth microdilution against 3,478 bacteria from 12 centers in Europe and Australia, with imipenem, cefepime, ceftriaxone, and piperacillin-tazobactam used as comparators. Ertapenem was the most active agent tested against members of the family Enterobacteriaceae, with MICs at which 90% of isolates are inhibited (MIC(90)s) of < or =1 microg/ml for all species. Ertapenem also was more active than imipenem against fastidious gram-negative bacteria and Moraxella spp.; on the other hand, ertapenem was slightly less active than imipenem against streptococci, methicillin-susceptible staphylococci, and anaerobes, but its MIC(90)s for these groups remained < or =0.5 microg/ml. Acinetobacter spp. and Pseudomonas aeruginosa were also much less susceptible to ertapenem than imipenem, and most Enterococcus faecalis strains were resistant. Ertapenem resistance, based on a provisional NCCLS MIC breakpoint of > or =16 microg/ml, was seen in only 3 of 1,611 strains of the family Enterobacteriaceae tested, all of them Enterobacter aerogenes. Resistance was also seen in 2 of 135 anaerobes, comprising 1 Bacteroides fragilis strain and 1 Clostridium difficile strain. Ertapenem breakpoints for streptococci have not been established, but an unofficial susceptibility breakpoint of < or =2 microg/ml was adopted for clinical trials to generate corresponding clinical response data for isolates for which MICs were as high as 2 microg/ml. Of 234 Streptococcus pneumoniae strains tested, 2 required ertapenem MICs of 2 microg/ml and one required an MIC of 4 microg/ml, among 67 non-Streptococcus pyogenes, non-Streptococcus pneumoniae streptococci, single isolates required ertapenem MICs of 2 and 16 microg/ml. These streptococci also had diminished susceptibilities to other beta-lactams, including imipenem as well as ertapenem. The Etest and disk diffusion gave susceptibility test results in good agreement with those of the broth microdilution method for ertapenem.

Evaluation of the MRSA-Screen Test in detecting oxacillin resistance in community and hospital isolates of Staphylococcus aureus.

The MRSA-Screen Test (Denka Seiken Co., Japan), a latex agglutination test to detect penicillin-binding protein 2a, was compared with PCR for the detection of oxacillin resistance in Staphylococcus aureus. A total of 77 oxacillin-sensitive and 269 oxacillin-resistant (ORSA) isolates were evaluated. Of the ORSA isolates, 186 were non-multiresistant (NORSA), defined as being resistant to two or fewer antibiotics other than beta-lactams. Eighty-three were multiresistant ORSA (MORSA) strains. If PCR is considered the gold standard test, then the sensitivity, specificity, positive and negative predictive values of the MRSA-Screen Test were 100, 99, 99 and 100%, respectively. The endpoint was hard to read with NORSA strains that took longer than 60 s to react. MORSA strains took a median 12 s (range 5-60 s) to give a positive reaction with the MRSA-Screen Test, whereas NORSA strains took a median 30 s (range 5-180 s), a difference which was significantly different (P < 0.0001, two-tailed Mann-Whitney unpaired two sample test). NORSA strains had an MIC50 of 128 mg/l and MIC90 of 256mg/l, whereas MORSA strains had an MIC50 and MIC90 of >256mg/l. The time that the MRSA-Screen Test took to agglutinate with ORSA strains correlated weakly with the MIC (r2 = 0.26). Detection of methicillin resistance cost AUD$9 per isolate with the MRSA-Screen Test, compared with AUD$13 per isolate with mecA PCR. The MRSA-Screen Test gave excellent sensitivity and specificity, and was quicker and cheaper than PCR. The full 3 min should be allowed to elapse before calling a test negative. Organisms giving indeterminate reactions should be tested for the mecA gene by PCR.

Mitochondrial glutathione and oxidative stress: implications for pulmonary oxygen toxicity in premature infants.

Administration of supplemental oxygen, despite being an important clinical therapy, can cause significant lung damage. Because they have underdeveloped lungs, prematurely born human infants frequently require supportive therapies that employ elevated oxygen concentrations, which put them at risk for developing pulmonary oxygen toxicity. This risk is made even greater by the immaturity of their cellular antioxidant defenses. Although the exact mechanisms of oxygen toxicity are still not fully defined, cellular damage is probably mediated by increased production of chemically reactive oxygen species (ROS) in the mitochondria. Cellular protection against ROS is provided by a variety of antioxidant molecules and enzymes, including the glutathione (GSH)-dependent antioxidant system. The GSH-dependent antioxidant enzyme system provides vital cellular protection against ROS, particularly hydrogen peroxide and certain organic hydroperoxides, under pathological and toxicological conditions, by using selenium-dependent and -independent peroxidases to reduce hydrogen peroxide or lipid peroxides to water or the respective alcohols, with the concurrent oxidation of GSH to glutathione disulfide (GSSG). In the mitochondria, limitations of GSH synthesis and transmembrane transport suggest that optimal functioning of the mitochondrial GSH system, and maintenance of adequate thiol-disulfide redox tone is essential to protect against the injurious effects of ROS. Manipulation of endogenous GSH concentrations can alter cellular responses to oxidant injury. Beneficial effects are evident when intracellular GSH concentrations are increased. In conditions that increase mitochondrial production of ROS, such as exposure to high concentrations of oxygen, therapies based on enhancing mitochondrial GSH concentrations could be highly beneficial.

Cardiac troponin: a new serum marker of myocardial injury in sepsis.

OBJECTIVE: Echocardiogram-derived left ventricular ejection fraction (LVEF) is usually utilized to evaluate left ventricular function, including that of septic patients. However, LVEF is greatly influenced by afterload. The aim of this study was to test the hypothesis that troponin I, a serum marker of myocardial injury, may be able to detect left ventricular involvement by the septic process, being at least as sensitive an indicator of left ventricular dysfunction as LVEF in these patients. DESIGN: Comparison of echocardiogram-derived LVEF with serum levels of troponin I in ten critically ill septic patients. SETTING: General intensive care unit in a tertiary care private hospital. PATIENTS: Ten critically ill septic patients with no previous documented heart disease. MEASUREMENTS AND RESULTS: Patients were simultaneously submitted to a two-dimensional echocardiogram and troponin I determinations. LVEFs and troponin I levels were analyzed in a two-by-two table in order to validate troponin I as a new biochemical marker of myocardial injury in sepsis. All the patients whose LVEF was < 0.5 had elevated troponin I levels (kappa = 0.61, p = 0.035). CONCLUSIONS: Identification of myocardial dysfunction in septic patients has been a challenging task. Troponin I, a serum marker of myocardial injury, may be of great help in the recognition of myocardial involvement by sepsis in a noninvasive and readily available way.

A national collaborative study of the in vitro activity of oral cephalosporins and loracarbef (LY 163892). Australian Group for the Study of Antimicrobial Resistance (AGAR).

A national collaborative study involving the laboratories of 17 Australian hospitals examined the in vitro activity of loracarbef, cefaclor, cephalexin, amoxycillin and amoxycillin/clavulanate against 2661 recently isolated common bacterial pathogens. Loracarbef was the most active agent against Escherichia coli (MIC90 = 1 mg/l) and had activity comparable to other agents against Klebsiella pneumoniae and Proteus mirabilis. Like the oral cephalosporins, it had no activity against species of Enterobacter and Serratia. beta-lactamase-producing Staphylococcus aureus and Haemophilus influenzae were moderately sensitive to loracarbef (MIC90 = 8 mg/l for both species). Streptococcus pneumoniae was moderately sensitive to loracarbef (MIC90 = 2 mg/l) but strains which were insensitive to penicillin were often highly resistant.

Multi-centre collaborative study for the in vitro evaluation of new macrolides dirithromycin and erythromycylamine. Australian Group for Antimicrobial Resistance (AGAR).

A national study was conducted to determine the in vitro activity of 2 newer macrolides, dirithromycin and erythromycylamine compared with that of erythromycin, tetracycline and penicillin. Nineteen major teaching hospitals participated in the study. Minimal Inhibitory Concentrations (MICs) were determined by agar dilution, mostly using Iso-Sensitest Agar and an inoculum of 10(4) cells per spot. 2284 clinically significant strains were isolated in late 1991 and early 1992, comprising 1736 Gram-positive cocci, 355 Haemophilus influenzae, 97 Moraxella catarrhalis, 32 Listeria monocytogenes, 25 Neisseria meningitidis and 39 Neisseria gonorrhoeae were tested. The study indicates that dirithromycin and erythromycylamine possess antibacterial activity equivalent to that of erythromycin against most Gram-positive cocci and M. catarrhalis. Strains resistant to erythromycin were also resistant to dirithromycin and to erythromycylamine. Tetracycline was as active as the macrolides against both penicillin-resistant and penicillin-susceptible strains of Staphylococcus aureus. Coagulase-negative penicillin-resistant staphylococci, compared with tetracycline, were relatively resistant to the macrolides. H. influenzae was less susceptible than the Gram-positive cocci.